andrographis periculata ness

Final Presentation on Research Proposal

Title : A Phase II clinical study of the effectiveness of

Andrographis paniculata (Burn.f.) Nees in the

treatment of erectile dysfunction y

F lt f M di i Kh K U i it Th il d

Presentor : Kutcharin Phunikhom

Faculty of Medicine KhonKaen University, Thailand2010

1

International Short Course Training in Research

Methodology and Biostatics 2010

Final Proposal

Title

A Phase II clinical study of the effectiveness of Andrographis paniculata

(Burn.f.) Nees in the treatment of erectile dysfunction

Presenter

Kutcharin Phunikhom, MD

Faculty of Medicine, Khonkaen University

Thailand 2010

Advisor

Assoc.Prof. Sumitr Sutra, MD

Assoc.Prof.Bandit Thinkhamrop, Ph.D.

2

Contents Page

Background and rationale 3 Literature review 4 Justification to do the study 9 Research question 10 Objective of the study 10 Hypothesis 10 Conceptual framework 11 Key works and operational definitions 12 Research Methodology 13 Outcome variables 14 Measurement of the outcome (data collection) 14 Statistic component 16 Data collection form 19 Variable to be measured 20 Data presentation and plan of data analysis 21 Ethical consideration 27 Time schedule 30 Budget 31 Case report form 33 Data layout 38 References 39 Appendix 1 IIEF 41

Appendix 2 Modified SHIM IIEF-5 51

Appendix 3 SF-36 54

3

Background and rationale

Magnitude of the problem

Erectile dysfunction (ED) was defined as the persistent inability to achieve and

maintain erection sufficient for normal sexual satisfaction. ED should be distinguished from

problem with ejaculation, libido and orgasm. ED is a common physiological disorder (degree

of the dysfunction are chronic, occasional and situational). The incidence and prevalence is

high worldwide, affects about 52% of men age 40-70 years old, about 26 new case annually

per 1,000 men, affecting an estimated 150 million men worldwide (Morales,2009). Age,

smoking and obesity are the main risk factors. In about 20% of case, psychological problems

are the causes and other are organic causes, some of the organic causes are shown in figure 1.

Organic erectile dysfunction and cardiovascular disease share the same risk factors, including

diabetes, hypertension, dyslipidemia, obesity and smoking. These conditions also share the

same pathophysiology with endothelial dysfunction, inflammatory and endothelial-

prothrombotic activity and oxidative stress being their common denominators. Among the

three main line treatments for ED consist of oral therapy, self-injection therapy (papaverine,

prostaglandine E1 and phentolamine) and penile prosthesis implantation. Although many

treatments for ED are available, patients seem to prefer oral medication. Oral therapy is

always the first option. Sildenafil (Viagra) is the first available effective oral agent for ED.

Impact on health care

Although erectile dysfunction is a benign disorder. It is frequently associated with loss

of self esteem and can impact significantly on the quality of life of sufferers, partners and

family. It is important also to consider the physical and psychological health of the suffer.

4

Sildenafil (Viagra) is the first effective oral agent for ED since March 1998 by Pfizer, but this

drug is very expensive and increase adverse event in some patient. Patients also may prefer

herbal medicines for many reasons, including relatively low cost, ready availability and safety.

Further development of phytochemical studies of widely know herbal plants are desired.

Furthermore, there seems to be a large population that prefers to use phytotherapies rather

than pharmaceutical drugs for this health problem.

Figure 1 Some organic cause of erectile dysfunction show in pie graph.

Literature review

Andrographis paniculata(Family Acanthaceae) (figure 2) commonly known

worldwide as “ King of Bitters” and “Fah Talai Jone” in Thailand (Li et al.,2007) is a

traditional medicine used extensively in Southeast Asia, India, Scandinavia and China. It has

been known to possess widerspread traditional application in the treatment of cold, fever,

laryngitis and infection. In Thailand, the aerial part of the plant (leaves and stems) are

normally used for extraction of the active phytochemicals to treat gastrointestinal tract and

upper respiratory infection, fever, herpes, sore throat and a variety of other chronic and

organic cause of erectile dysfunction

DM 40%

vascular disease 30%

Radical surgery 13%

Spinal cord injury 8%

Endrocrinal disease 6%

Multiple sclerosis 3%

5

infectious disease(Standard of Thai Herbal Medicine,1999). The fresh and dry leaves as well

as the juice of the whole plant are widely used. The major of bioactive component of

Andrographis paniculata is andrographolide, its structure is shown in figure 3.

Figure 2 Andrographis paniculata(Burn.f.)Nees. Figure 3 Biochemical structure of

andrographolide (Ruengsitagoon, 2005)

Pharmacological properties of andrographolide has been reported in both animal and

human, such as anti-platelet aggregation (Amroyan et.al.,1999; Thisoda e.al.t,2006), anti-

inflammatory (Suebsasana,2009; Shen et.al.,2002), anti-allergic(Xia.et.al,2004; Chandrase

karan et.al.,2010), antiviral:HIV(Reddy et.al.,2005; Wiart et.al.,2005), hepatoprotective

(Singha et.al.,2007), anti-diabetes (Reyes-Balanguer et.al., 2005; Yu et.al.,2008), stimulate

insulin secretion (Wibudi et.al.,2008), antithrombotic activity(Thisoda et.al.,2006), anti-

diabetic nephropathy (Lee et.al.,2010), treatment of common cold and respiratory

inflammation (Thamlikitkul et.al.,1991). Recently study in animal model showed that

andrographolide have effects on reproductive system, enhancing of sexual potency increasing

percentage of active form of spermatozoids and increasing of testosterone hormone level

(Sattayasai et.al.,2010) show in table 1.

Dosage and pharmacology of Andrographis paniculata in report of systematic review,

andrographolide 48-360 mg/day for treatment of upper respiratory infection. Rheumatoid

6

arthritis used 90 mg/day. Androgapholide was quickly and completely absorption, plasma

protein binding was 55 %, peak plasma 1.5-2 hrs, haft-life 6 hrs. and duration 10 hrs.

Metabolism by liver by conjugation and excretion by urine and faeces. Adverse drug reaction

were mild, infrequency and self-limiting (allergy, fatique, headache, nausea, diarrhea, metallic

taste, lymph node pain).

Mechanism of action of andrographolide

Sattayasai et.al(2010) study described mechanism of andrographolide action for

erection are two periods, in acute period are increased mounting frequency in three hours after

oral administration by antagonized alpha- one receptor due to relaxation of vascular smooth

muscle. In chronic period are increased testosterone level in four weeks but unknown

mechanism.

7

Table 1 Pharmacological property of andrographolide(AP1) on reproductive system.Author/yrs./title participants Dose/duration outcome Allan JJ et.al.(2009) Reproductive and fertility effects of an extract of AP in male Wistar rats

Male Wistar rats Per oral APE 20, 200, 1000 MKD for 65 day

-no effect on fertility -no effect on total sperm count & motility

Panossian A et.al.(1999) Effect of AP extract on progesterone in blood plasma of pregnant rats

Pregnant rats Per oral APE 200, 600, 1000 MKD For 19 day

Dose not exhibit any effect on the elevated level of progesterone in the plasma of rats

Akbarsha MA et.al.(2000) Aspects of the male reproductive toxicity/male antifertility property of AP1 in Albino rats: effect on the testis and the cauda epididymidal spermatozoa

Albino rats Per oral AP1 25, 50 MKD for 48 day

-Decreased sperm count -not motile spermatozoa -abnormality of sperm

Sattayasai J et.al.(2010) Effects of AP1 on sexual functions, vascular reactivity and serum testosterone level in rodents

Male ICR mice Per oral AP1 50 MKD daily for 8 wks

-180 min: increase mounting frequency -4 wks: increased testosterone -8 wks: no significant effect on sperm morphology & motility

Mkrtchyan A et.al.(2005) A phase I clinical study of AP fixed combination Kan Jang versus ginseng and valerian on the semen quality of healthy male subjects

Healthy male Per oral AP1 60, 120, 180 mg per day for 13 day

-The results of the study revealed no significant negative effect of Kan Jang on male semen quality and fertility, but rather a positive trend with respect to the number of spermatozoids in the whole ejaculate, the percentage of active (normokinetic) forms of spermatozoids, and fertility indexes, together with a decrease in the percentage of inactive (diskinetic) forms of spermatozoids and others reported a subjective feeling of enhanced sexual potency during the trial.

8

Table 2 clinical trial of andrographolide in other disease

Author/yrs/title participants Dose/duration outcome Amaryan G et.al(2003) Double-blind, placebo controlled, randomized pilot clinical trial of Immuno-Guard® -a standardized fixed combination of Andrographis paniculata Nees, with Eleutherococcus senticosus Maxime, Schizandra chinensis Bail. And Glycyrrhiza glabra L. extracts in patients with Familial Mediterranean Fever.

Familial Mediterranean Fever (FMF) 25 person

ImmunoGuard® 370 mg (andrographolide 4 mg) 4 tab three time /day (AP1 48 mg/day) 1 mouth

Significant less episodes FMF attacks in comparison with these on placebo

Saxena RC et.al(2010) A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmColdTM) in patients with uncomplicated upper respiratory tract infection.

223 URI patients KalmColdTM 200 mg/day (APE 30 mg: AP1 31.30 %w/w)

Reducing symptoms of URI ADR: vomiting, epitaxis, urticaria, diarrhea, nausea, lethargy

Burgos RA et.al.(2009) Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial.

RA patients 30/arm AP1 30 mg three time/day, 14 day

A significantly reduction for tender joint, number of swollen joints, total grade of tender joints ARD: headache, diarrhea, nausea, stomach discomfort, fatigue, common cold, pruritus/rash, cramp

Coon JT et.al.(2004) Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy.

Seven control trial Treatment 896 Placebo 1,235

AP1 48-360 mg /day (1-10 MKD)

Andrographis paniculata is superior to placebo in alleviating subjective symptoms of URTI ARD: mild, infrequent and reversible

Poolsup N et.al. (2004) Andrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract

3 trial 433 patients

APE (85-500 mg) 4 tab three time /day For 3-7 days

Andrographis paniculata more effective than placebo and may be an appropriate

9

infection: systematic review of randomized controlled trial.

alternative treatment of uncomplicated upper respiratory tract infection

Cui L et.al.(2005) Isolation and identification of seven glucoronide conjugates of andrographolide in human urine.

8 healthy volunteers

AP1( 50 mg/tab) 3 tab three time /day for 2 day (450 mg/day)

Seven conjugate metabolite in urine, determine by HPLC

Justification to do the study

Why do you have to do research?

There are mainly 3 reasons to do this study, as the followings

Firstly: Erectile dysfunction is a common problem of men in Thailand, same

worldwide. The study of “Levitra study no.10657-VENS” in 2001 and 2004 found erectile

dysfunction affect 43% of men age 40-70 years old, affect about 4 million Thai’s men (in

2000).

Secondly: Drugs treatment (three phosphodiesterase-5 inhibitor: vardenafil (Levitra

2.5-20 mg), sidenafil(Viagra 25-100 mg) and tadatafil(Cials 5-20 mg) of erectile dysfunction

are very expensive, few people can affect it.

Lastly: Andrographis paniculata or “Fah Talai Jone” is a healthy food, extensively

used in Thailand in the treatment of many illness. That it demonstrate the positive effect on

ED in men, it may be the benefit for Thai people and worldwide.

10

What should be the benefit from doing that?

Fah Talai Jone is traditional Thai herb plant, used for treated of cold and antipyretic.

If it can improve erection in men, it will be benefit for root grass people regarding widely

available, low cost and low adverse event.

Research question

Primary question: Can per oral daily dose 60 and 120 mg of andrographolide from

Andrographis paniculata Nees for 4 weeks increase 20%(IIEF-5 score) erection in erectile

dysfunction’s men?

Secondary question: How andrographolide effect testosterone hormone and

cholesterol?

Objectives of the study

1. To examine the treatment effectiveness of Andrographis paniculata (Burn. f.) Nees

in the patient with erectile dysfunction.

2. The secondary goals were to determine if there are any changes in both

testosterone hormone level and lipid profiles of the treated patient.

Hypothesis

Ho : Andrographolide have same effect to placebo in erectile dysfunction.

HA : Andrographolide have superior effect to placebo in erectile dysfunction.

11

Conceptual framework

12

Key words and operational definitions

Erectile dysfunction, Impotence, Andrographis paniculata, Angrographolide

Operational definition :

ED : erectile dysfunction, assessment by self-report on the IIEF-5. IIEF-5

(International Index of Erectile Function Questionnaire) is a questionnaire for assessment

erectile function. These questions ask about the effects patients erection problems have had

on sex life, over the past 4 weeks. IIEF-5 compost of 5 questions about sexual activity, 6

score per one question (0-5) and interpret erectile function depend on score:

Table 3 Interpreted of IIEF-5

IIEF-5 score Erectile function 22-25 normal erectile function 17-21 mild erectile dysfunction 12-16 mild to moderate erectile dysfunction 8-11 moderate erectile dysfunction < 7 severe erectile dysfunction

Andrographolide : The main active compound of Andographis paniculata , extract from the

aerial part of the plant.

13

Table 4 Description of the IIEF questionnaire

Dimensions Number of items

Cluster of items

Directions of dimensions

Erectile function(EF) 6 1,2,3,4,5,15 1-10 severe erectile dysfunction 11-16 moderate dysfunction 17-21 mild to moderate dysfunction 22-25 mild dysfunction 26-30 no dysfunction

Orgasmic function(OF) 2 9-10 High score = Less dysfunction Sexual desire(SD) 2 11-12 Intercourse satisfaction(IS) 3 6,7,8 Overall satisfaction 2 13,14

Research Methodology

Study design: Experimental study, prospective, phase II clinical trial Setting: Srinagarind hospital, faculty of medicine, KhonKaen university, Thailand

Target population: Patients with ED visiting at out-patient department of study site. Sampling technique : Consecutive impotence patients who attend OPD andrology during study period. Eligible criteria

Inclusion criteria

1. Men age 40-70 years old in the andrology clinic at Srinagarind hospital with mild to

mild-moderated erectile dysfunction (as judged by IIEF-5 score 12-21)

2. A stable sexual partnership during the previous 6 month.

14

Exclusion criteria

1. Patients who included history of radical prostatectomy, spinal cord injury,

neurological impairment, Peyronie’s disease, drug abuse and specific previous

treatment.

2. Patients who included history of severe psychological problem.

3. Impaired renal and hepatic function.

4. Current ischemic heart disease (6 months ago).

Randomization : Computer generated random sequences using block randomization and will be placed in the opaque sealed envelopes. Intervention and assessor masking : Andrographolide and placebo will be prepare by same color of capseal and will be dispensed in identical blister, labeled with code numbers only.

Outcome variables Primary outcome: improvement of erection measured by IIEF. Secondary outcome: measure testosterone level and lipid profile before and after treatment, quality of life assessment by SF-36

Measurement of the outcome (data collection) How do you measure the outcome?

1. IIEF score for assess improvement of erection. 2. SF-36 score for assess quality of life. 3. Measurement of testosterone level by RIA

15

Study flow:

When do you collect the data?

1. Self –report on the IIEF pre-treatment and 1, 2, 3 and 4 weeks post treatment 2. Self-report on SF-36 at 4 weeks post treatment.

Intervention performers Clinician: -Diagnostic ED -enrollment -evaluate outcome and assessment of adverse reaction.

-Provided signed informed consent after enrollment.

16

Registered nurse in OPD: -Performed baseline and eligibility assessments -open box set and sealed envelope to assigned patient to treatment group Pharmacist: -Prepare andrographolide and placebo by capseal them, identically and were dispensed in identical blister, labeled with code number only. Which tool will be used

IIEF and SF-36 questionnaire

Statistic component Sample size calculation This study is a phase II of clinical trial, the number of participant in phase II about 20-300.The primary outcome is the improvement of erectile function that measurement by IIEF-5 score, compare between treatment and placebo group, because of this study is combination phase IIA (assess dosing requirement) and phase IIB (study efficacy). We used the following assumption to estimate the necessary sample size. The required sample size for difference between three mean for multiple comparison was estimate. A 5 score(minimum detectable different) of IIEF-5 was considered the smallest average difference change between andrographolide treated (at least one dosing effective [therapeutic dose (60 mg) or double dose (120 mg)] and placebo treatments to detect a clinical effect in a IIEF-5 score of 25 (equivalent to 20% improve in the treatment group). The power of 80% was used to detect a true difference in outcome between the placebo and the intervention group. The level of significance was set at 5% (reject Ho if p>0.05). The common standard deviation used in the sample size was 5 score of IIEF-5. The required sample size for each arm of AP1 60 mg, 120 mg or placebo was a minimum of 51 participant or a total 153 for the whole study. As drop outs are common in clinical trial of a self-limiting condition, around 20% more participants

17

were added in each group, estimating 62 participants per group(total 186). The sample size is calculated by PASS 2008 software.

Data analysis

Baseline characteristics of the participants and operative data in this study are

-Age (years)

-BMI (kg.m-2)

-Smoking (smoker /no smoker)

-Alcohol drinking (no/ yes)

-Underlying disease (DM/ HT/ CHD)

-Time period with ED (years)

-Exercise (no/yes, frequency)

And baseline laboratory analysis compost of

-CBC

-Blood chemistry (BS, HbA1C, BUN, Cr, Liver enzyme, Lipid profile)

-Testosterone level

-Urinalysis

-EKG

18

All data relevant to the study will carefully entered onto the CRF maintained for each participant who had received trial medication. Data will managed using a Microsoft Excel 2007 based database.

For continuous data such as age, BMI, time period of ED and laboratory test will be presented using mean and standard deviation and categorical data such as smoking, alcohol drinking and underlying disease will be presented as number and percentage for each group. If these data are significant difference in both groups (treatment and placebo), subgroup analyze will be done.

Erection is the main outcomes, will be measure by IIEF questionnaire at pre-treatment and 1, 2, 3 and 4 weeks (post-treatment), data will be recorded as continuous data and presented as mean of IIEF score+ SD. The effect of each treatment will calculated as the increasing in the IIEF score from baseline to final assessment. The mean difference in effect between AP1 60 mg, 120 mg and placebo will be estimate. In the pooling of mean difference as well as the estimation of 95% confidence interval and p-value. Comparison total and individual IIEF score recorded at different time (pre/week1,2,3,4 post treatment) between groups will analyzed using repeated measure ANOVA.

Statistical comparisons of quality of life between group by SF-36

questionnaire (post treatment) will be conducted using Kruskal-Wallis rank test.

H0 : u1=u2=u3

HA : u1#u2#u3

19

Data collection form

Subject Number -

-

Subject Initial

ID

1. Age………….yrs AGE

2. Weight………..kg WT 3. Height…………cm. HT 4. BMI …………..kg.m-2 BMI 5. Smoking Habit 0 Non-smoker 1 Ex-smoker 3 Smoke……..number/day

SMK

6.Alcohol Drinking 0 Never 1Occasionally 2 Often ………glass/week

ALC

7. Exercise 0 No 1Occasionally(1-3 day/wk) 2 Often (4-7day/week)

EXC

8. Underlying disease 0 No

1 Yes, specific 2 DM3HT4CHD

UD

9. Time period with ED………… year ED

20

Variable to be measured are

Baseline data

Variables Type of data scale

Age (years) continuous Ratio

BMI (kg.m-2) continuous Ratio

Smoking Habit categorical Nominal

Alcohol Drinking categorical Nominal

Exercise categorical Nominal

Underlying disease categorical Nominal

Time period with ED(year) continuous Ratio

Primary outcome


IIEF scale continuous ratio

21

Secondary outcome


Testosterone level continuous ratio

Lipid profile (cholesterol,

triglyceride, HLD, LDL)

continuous ratio

SF-36 scale continuous ratio

Data presentation and plan of data analysis

Dummy Tables

Table 1 Baseline characteristics of the participant (data are present as mean +SD or

number of participant)

variables placebo AP1 60 mg aP1 120 mg

Age (years)

BMI (kg.m2)

Exercise

Mean +SD

Mean +SD

N,%

Mean +SD

Mean +SD

N,%

Mean +SD

Mean +SD

N,%

22

Smoking

Alcohol

Underlying

Time for ED(years)

N,%

N,%

N,%

Mean +SD

N,%

N,%

N,%

Mean +SD

N,%

N,%

N,%

Mean +SD

Table 2 Comparison of pre- and post-treatment IIEF score of the participant (data are

present as mean + SD, calculate magnitude of effect pre &post treatment with 95%CI, p-value

and comparison IIEF score post-treatment between three group by using ANOVA)

variables placebo AP1 60 mg AP1 120 mg Pre-Tx( IIEF wk0) Post-Tx (IIEF wk4) Mean different 95% CI P-value

Mean +SD Mean +SD x1 Y1,z1 0.0xxx



AP1=andrographolide

Table 3 Comparison of IIEF score, pre(week 0) and post treatment(week 4) of the

participant

variables placebo AP1 60 mg AP1 120 mg IIEF score-pre Mean +SD Mean +SD* Mean +SD**

23

post Erectile Function -pre -post Orgasmic Function-pre -post Sexual Desire -pre -post Intercourse Satisfaction-pre -post Overall Satisfaction-pre -post

Mean +SD Mean +SD Mean +SD*** Mean +SD Mean +SD Mean +SD Mean +SD Mean +SD Mean +SD Mean +SD Mean +SD



*Symbol were found to be significantly different (one way ANOVA) from placebo

**Symbol were found to be significantly different (one way ANOVA) from AP1 60

mg

Table 4 Quality of life by SF-36 will be conducted using Kruskal-Wallis rank test

group n Mean +SD p-value

Placebo

AP1 60 mg

AP1 120 mg

xx

xx

xx

Mean +SD

Mean +SD

Mean +SD

0.0xx

0.0xx

0.0xx

24

Table 5 Comparison laboratory value, testosterone and lipid profile data are present as

mean + SD and comparison three group by using ANOVA)

Outcome placebo AP1 60 mg AP1 120 mg p-value

Testosterone, Mean(+SD)

Pre-treatment

Post-treatment

Cholesterol, mean(+SD)

Pre-treatment

Post-treatment

Triglyceride, mean(+SD)

Pre-treatment

Post-treatment

HDL-C, mean(+SD)

Pre-treatment

Post-treatment

LDL-C, mean(+SD)

Pre-treatment

Post-treatment

25

Data presentation

Table 1 demographic data

variables placebo AP1 60 mg AP1 120 mg

Age (years)

BMI (kg.m2)

Exercise (yes)

Smoking (yes)

Alcohol (yes)

Underlying (yes)

Time for ED(years)

Severity of ED

-mild (12-16)

-mild-moderate(17-21)

Mean +SD

Mean +SD

N,%

N,%

N,%

N,%

Mean +SD

N,%

N,%

Mean +SD

Mean +SD

N,%

N,%

N,%

N,%

Mean +SD

N,%

N,%

Mean +SD

Mean +SD

N,%

N,%

N,%

N,%

Mean +SD

N,%

N,%

26

Table 2 magnitude of IIEF score, pre- and post-treatment of the participant

variables placebo AP1 60 mg AP1 120 mg Pre-Tx (IIEF wk0) Post-Tx (IIEF wk4) Mean different 95% CI P-value

Mean +SD Mean +SD X1 Y1,z1 0.0xxx



*Symbol were found to be significantly different

Table 3 Comparison of IIEF score, pre and post treatment of the participant

IIEF treatment Week0

Mean score

Week1

Mean score

Week2

Mean score

Week3

Mean score

Week4

Mean score

Mean

difference

(wk4-wk1)

p-value

IIEF Placebo

AP60

AP120

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

IIEF-5 Placebo

AP60

AP120

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

OF Placebo

AP60

AP120

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

SD Placebo

AP60

AP120

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

IS Placebo Mean +SD Mean +SD Mean +SD Mean +SD Mean +SD Mean +SD

27

AP60

AP120

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

OS Placebo

AP60

AP120

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

Mean +SD

*Symbol were found to be significantly different (repeated measure ANOVA)

Table 4 Quality of life by SF-36 (Kruskal-Wallis rank test)

group n Mean +SD p-value

Placebo

AP1 60 mg

AP1 120 mg

xx

yy

zz

Mean +SD

Mean +SD

Mean +SD

0.0xx

0.0xx

0.0xx

Ethical consideration

This study protocol compost of the study information and consent form must be

accepted by the ethic committee of medicine faculty, Khon Kaen University before starting

the recruitment of all participants into the study. All participants will receive adequate verbal

and written information regarding the study and information about the purpose, process,

28

advantages and adverse reaction of andrographolide before they decide to participate in the

study. The investigator must be responsible for obtaining the appropriate consent form from

the participants before recruiting them into the study.

All participants that meet the eligible criteria will be enrolled in this study and

randomized for each intervention. The refusal of a patient to participate in a study must never

interfere with the patient-physician relationship.

Limitation of this study

1. Srinagarind hospital is a tertiary care hospital, the participants with erectile

dysfunction are likely to have more severe disease than would be expected in the

generation population.

2. Erectile dysfunction is special problem but no life threatening, many patient no

need specific treatment, may be have compliance problem.

3. Information bias may occur in some patient because of IIEF is a self-questionnaire

measurement.

Possible benefits

As shown in justification, ED is common problem in worldwide and specific treatment

are very expensive. If andrographolide prove to be effective treatment for ED, many patient

may have low cost treatment for ED.

29

Possible harm

Possible harms from this treatment are expected to be low because of this plant used

commonly known worldwide as “ King of Bitters” and “Fah Talai Jone” in Thailand(Li et

al.,2007). Andrographis paniculata is a traditional medicine used extensively in Southeast

Asia, India, Scandinavia and China. It has been known to possess widerspread traditional

application in the treatment of cold, fever, laryngitis and infection. Report of adverse even are

mild, low incidence and self limited.

Patient protection and management

Written informed consent will be done by every patient and/or authorized

representative on a voluntary basis. The details of the study will be provided transparently.

The participants can refuse to join the study at any time without conditions and not affect on

those patients care and management.

For safety of the participants, the patients with history of Andrographis paniculata

shall be excluded.

Compensation

There is no compensation for the participants of the study.

Responsible person

30

Kutcharin Phunikhom, MD.

Department of pharmacology, faculty of medicine, Khon kaen University

043-348397, 081-7178751

Time schedule

The study will be conducted between November 2010 and June 2011

Activity Nov.-Dec 2010 Jan-Feb 2011 Mar-Aug 2011 Sep-Oct 2011

protocol

development

/

Ethics

application

/ /

Recruitment of

data collection

/ / /

Analysis / / /

Report writng

and publication

/ /

31

Budget

Detail Cost X unit(S) Baht

Lab testing (in table below) 2550 X 186 474,300

Drug preparation 120 X 186 22,320

Patient travel 500 X 186 93,000

Data collection form preparation 3500

Office supplies 3000

Patient tracing (telephone call) 3000

Report preparation 3000

miscellaneous 2000

Total funding project 604,120

Lab testing

Lab test Pre-treatment (baht) Post-treatment (baht)

BS

HbA1C

BUN

40

150

50

40

150

50

32

Creatinine

Cholesterol

Triglyceride

HDL

LDL

CBC

Liver enzyme(ALT,AST,AP)

Testosterone

UA

EKG

50

60

60

100

150

90

150

250

50

200

50

60

60

100

150

90

150

250

-

-

total 1,400 1,150

33

Case report form

I will separate CRF in 2 part, pre-treatment and post treatment

Demographic and other information: pre-treatment Code

1. Number……………..initial…………………..

2. Age……….yrs

3. BW…………….kg, HT…………….cm.

4. BP……..mmHg, HR……../min, PR………./min

5. Smoking ……0………1……….2

6. Alcohol………0………..1……….2

7. Underlying……0……….1………2………3………4

8. Exercise………0……….1………..2

9. Time period with ED…………..yrs

10. CBC , Hb…….mg%, Hct……vol%, Plt…………..cell/dL

11. BS……..mg/dL, HbA1C………..mg%

12. BUN…………mg/dLCr………..mg/dL

13. ALT…………U/L, AST…………..U/L, AP……………..U/L

14. Urinalysis….0……..1

15. EKG……0……….1

34

16. Cholesterol………….mg/dL, Triglyceride……………mg/dL

HDL………………..mg/dL, LDL……………………mg/dL

17. Testosterone level……………..mIU/dL

18. IIEF score…total

IIEF-5…………..

EF………………

OF………………..

SD……………..

IS………………..

OS…………………

Demographic and other information: post-treatment Code

1. Number……………..initial…………………..

2. BW…………….kg, HT…………….cm.

3. BP……..mmHg, HR……../min, PR………./min

4. CBC , Hb…….mg%, Hct……vol%, Plt…………..cell/dL

5. BS……..mg/dL, HbA1C………..mg%

6. BUN…………mg/dLCr………..mg/dL

35

7. ALT…………U/L, AST…………..U/L, AP……………..U/L

8. Urinalysis….0……..1

9. Cholesterol………….mg/dL, Triglyceride……………mg/dL

HDL………………..mg/dL, LDL……………………mg/dL

10. Testosterone level……………….mIU/dL

11. IIEF score…total

IIEF-5…………..

EF………………

OF………………..

SD……………..

IS………………..

OS…………………

12. SF-36 score……………………………..

Data dictionary

Questionnaires Details Code

id Identification number 001 to 064

age Age Age in years based on birthday

36

wt Body weight Body weight in kilogram

ht Body high Body high in centimeter

BMI Body mass index

=BW(kg)/Ht(m)2

BMI in kg.m-2

SMK Smoking status 0=no smoking

1=experience of smoking

(stop>6 mouth)

2=current smoking

ALC Alcohol drinking 0=no drinking

1=occasional drinking (<3 day/week)

2=often drinking(>3 day/week)

EXC Exercise 0=no exercise

1=occasional exercise (<3 day/week)

2=often exercise (>3 day/week)

UD Underlying disease 0=no underlying

1=have underlying

2=DM, 3=HT, 4=CHD

ED Time period with ED Time in years

37

IIEF IIEF score Score 5 to 75

EF Erectile function Score 1 to 30

OF Orgasmic Function Score 0 to 10

SD Sexual Desire Score 2 to 10

IS Intercourse Satisfaction Score 0 to 15

OS Overall Satisfaction Score 2 to 10

SF-36 Short form quality of life

assessment score

Score 35 to 149

CHO Cholesterol level Cholesterol level in mg/dl

TG Triglyceride Triglyceride in mg/dL

HDL HLD HLD in mg/dL

LDL LDL-C LDL-C in mg/dL

TES Testosterone level Testosterone level in mIU/dL

UA Urinalysis 0 = normal or no clinical significant

1= abnormal

EKG Electrocardiography 0 = normal or no clinical significant

1= abnormal

38

Data layout

id age bmi smk alc exc ud ed IIEF EF OF SD IS OS SF cho tes

001

002

003

…

n

39

References

1. Akbarsha MA, Murugaian P. Aspects of the Male reproductive toxicity/Male antifertility property of andrographolide in Albino rats: effect on the testis and the cauda epididymidal spermatozoa. Phytother Res 2000; 14: 432-5.

2. Allan JJ, Pore MP, Deepak M, Murali B, Mayachari AS, Agarwal A. Reproductive and fertility effects of an extract of Andographis paniculata in male Wistar rats. Int J Toxicol 2009; 28: 308-17.

3. Amaryan G,Astvatsatryan V, Gabrielian E, Panossian A, Panossian V, Wikman G. Double-blind, placebo-controlled, randomized pilot clinical trial of ImmunoGuard® -a standardized fixed combination of Andographis paniculata Nees. with Eleutherococcus senticosus Maxim, Schizandra chinensis Bail. And Glycyrrhiza glabra L. extracts in patients with Familial Mediterranean Fever. Phytomedicine 2003; 10: 271-85.

4. Amaryan E, Gabrielian E, Panossian A, Wikman G, Wagner H. Inhibitory effect of andrographolide from Andographis paniculata on PAF-induced platelet aggregation. Phytomedicine 1999; 6:27-31.

5. Burgos RA, Hancke JL, Bertoglio JC, Aguirre V, Arriagada S, Calvo M, Caceres DD. Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial. Clin Rheumatol 2009; 28: 931-46.

6. Chandrasekaran CV, Gupta A, Agarwal A. Effect of an extract of Andographis paniculata leaves on inflammatory and allergic mediators in vitro. J Ethnopharmaco 2010; 129: 203-7.

7. Coon JT, Emst E. Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy. Planta Medica 2004; 70: 293-8.

8. Cui L, Qui F, Yao X. Isolation and identification of seven glucoronide conjugates of andrographolide in human urine. The American Society for Pharmacology and Experimental Therapeutics 2005; 33: 555-62.

40

9. Lee MJ, Rao YK, Chen K, Lee YC, Chung YS, Tzeng YM. Andographolide and 14-deoxy-11-12-didehydroandographolide from Andographis paniculata attenuate high glucose-induced fibrosis and apoptosis in murine renal mesangeal cell lines. J Ethnopharmaco (2010) article in press. Doi: 10.1016/j.jep.2010.07.057

10. Li J, Huang W, Zhang H, Wang X, Zhou H. Synthesis of andrographolide derivatives and their TNF-alpha and IL-6 expression inhibitory activities. Bioorg Med Chem Lett 2007; 17: 6891-4.

11. Medicinal Plant Research Institute. Standard of Thai herbal medicine: Andographis paniculata(Burn.f.) Nees. Thailand: The War Veterans Organization Press; 1999.

12. Mkrtchyan A, Panosyan V, Panossian A, Wikman G, Wagner H. A phase I clinical study of Andographis paniculata fixed combination Kan JangTM versus ginseng and valerian on the semen quality of healthy male subjects. Phytomedicine 2005;12:403-9.

13. Morales AM, Mirone V, Dean J, Costa P. Varidenafil for the Treatment of erectile dysfunction: an overview of the clinical evidence. Clin Intervention Aging 2009; 4: 463-72.

14. Panossian A, Kochikian A, Gabrielian E, Muradian R, Stepanian H, Arsenian F, Wagner H. Effect of Andographis paniculata extract on progesterone in blood plasma of pregnant rats. Phytomedicine 1999; 6: 157-61.

15. Poolsup N, Suthisisang C, Prathanturarug S, Asawamekin A, Chanchareon U.

Andrographis paniculata in the symptomatic treatment of uncomplicated upper

respiratory tract infection: systematic review of randomized controlled trial. Journal of

Clinical Pharmacy and Therapeutics 2004; 29: 37-45.

16. Reddy VL, Reddy SM, Ravikanth V, Krishnaiah P, Goud TV, Rao TP, Ram TS, Gonnade RG, Bhadbhade M, Venkateswarlu Y. A new bis-andographolide ether from Andographis paniculata nees and evaluation of anti-HIV activity. Nat Prod Res 2005; 19: 223-30.

41

17. Reyes-Balanguer J, Solaz-Moreno E, Morata-Aldea C, Elorza-Montesinos P. Spontaneous diabetic myonecrosis. Diabetes Care 2005;28: 980-1.

18. Ruengsitagoon W, Anuntakarun K, Aromdee C. Flow injection spectophotometric determination of andrographolide from Andographis paniculata. 2005 Elsevier B.V. All right reserved. Doi: 10.1016/j.talanta 2005.11.0.035

19. Sattayasai J, Srisuwan S, Arkaravichien T, Aromdee C. Effects of andrographolide on sexual functions, vascular reactivity and serum testosterone level in rodents. Food and Chemical Toxicology 2010; 48: 1934-8.

20. Saxena RC, Singh R, Kumar P, Yadav SC, Negi MPS, Saxena VS, Joshua AJ,

Vijayabalaji V, Goudar KS, Venkateshwarlu K, Amit A. A randomized double blind

placebo controlled clinical evaluation of extract of Andrographis paniculata

(KalmColdTM) in patients with uncomplicated upper respiratory tract infection.

Phytomedicine 2010; 17: 178-85.

21. Shen YC, Chen CF, Chiou WF. Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism(s) involved its anti-imflammatory effect. Br J Pharmaco 2002; 135: 399-406.

22. Singha PK, Roy S, Dey S. Protective activity of andrographolide and arabinogalactian proteins from Andographis paniculata Nees. against ethanol-induced toxicity in mice. J Ethnopharmacol 2007; 111:13-21.

23. Thamlikitkul V, Dechetiwongoe T, Theerapong S, Chantrakul N, Boonroi P, Punkrut W, Ekpalakorn W, Boontaeng N, Taechaiya S, Petcharoen S. Effecacy of Andographis paniculata,Nees for pharyngotonsillitis in adults. J Med Assoc Thai 1991; 74: 437-42.

24. Thisoda P, Rangkadilok N, Worasuttayangkurn L, Ruchirawat S, Satayavivad J. Inhibitory effect and its active diterpenoids on platelet aggregation. Eur J Pharmacol 2006; 553:39-45.

42

25. Wiart C, Kumar K, Yusof MY, Hamimah H, Fauzi ZM, Sulaiman M. Antiviral properties of ent-labdene diterpenes of Andographis paniculata Nees, inhibitors of herpes simplex virus type I. Phytother Res 2005;19: 1069-70.

26. Wibudi A, Kiranadi B, Manalu W, Winarto A, Suyono S. The Traditional Plant, Andographis paniculata(Sambiloto), Exhibits Insulin-Releasing Action in Vitro. Acta Med Indones-Indones J Intern Med 2008; 40: 63-8.

27. Xia YF, Ye BQ, Li YD, Wang JG, He XJ, Lin X, Yao X, Ma D, Slungaard A, Hebbel RP, Key NS, Geng JG. Andrographolide attenuates inflammation by inhibition of NF-kappa B activation through covalent modification of reduced cysteine 62 of p50. J Immunol 2004; 173: 4207-17.

28. Yu BC, Chang CK, Su CF, Cheng JT. Mediation of beta-endorphin in andrographolide-induced plasma glucose-lowering action in type I diabetes-like animal. Naunyn Schmiedeberge Arch Pharmacol 2008; 377: 529-40.

43

Appendix 1

แบบสอบถามประเมนสมรรถภาพทางเพศ

ID………….Initial………………ตอบ ณ วนท............เดอน.........................พ.ศ.......................

Visit ...........ครงแรก............สปดาหท 1..........สปดาหท 2...........สปดาหท 3.........สปดาหท 4

ค าถามตอไปน ถามเกยวกบผลตอการด ารงชวตทางเพศของทานทเกดเนองมาจากปญหา

การแขงตวของอวยวะเพศในชวงสปดาหทผานมา(ชวง 4 สปดาหทผานมาในกรณตอบครงแรก)

โปรดตอบค าถามอยางซอสตยและชดเจนเทาทจะท าได โปรดตอบทกค าถามโดยกา

เครองหมาย / ลงในชองสเหลยม ถาทานไมแนใจวาจะตอบอยางไรด โปรดใหค าตอบทดทสดท

ทานสามารถจะท าได

ค าจ ากดความ

การรวมเพศ หมายถง การลวงล าเขาไปในชองคลอดของคนอน

กจกรรมทางเพศ หมายถง การรวมเพศ การกอดจบประเลาประโลม การกระตนใหม

ความรสกทางเพศกอนรวมเพศและการส าเรจความใครดวยตวเอง

การหลง หมายถง การหลงน าอสจออกมาจากอวยวะเพศชาย(หรอม

ความรสกเสมอนม)

44

การปลกเราทางเพศ หมายถง การเลาโลมคนอนดวยการสมผสตามรางกายรวมทง

บรเวณอวยวะเพศ การดภาพกระตนความรสกทางเพศ ฯลฯ

1. ตลอด ( 4) สปดาหทผานมา อวยวะเพศของทานสามารถแขงตวไดบอยครงเพยงใดใน

ระหวางทมกจกรรมทางเพศ

ไมมกจกรรมทางเพศเลย............................................

เกอบทกครง หรอทกครง............................................

บอยครง (มากเกนครง) ............................................

บางเวลา (ประมาณครงหนง).....................................

นานๆครง (นอยกวาครง)...........................................

เกอบจะไม หรอไมเลย...............................................

2. ตลอด (4) สปดาหทผานมา เมออวยวะเพศของทานแขงตวเมอไดรบการปลกเราทางเพศ

บอยแคไหนทอวยวะเพศของทานจะแขงตวมากพอทจะสอดใสเขาไปในชองคลอด

ไมมการปลกเราทางเพศเลย............................................






45

3. ตลอด (4) สปดาหทผานมา เมอทานพยายามรวมเพศ บอยแคไหนททานสามารถสอดใส

(ลวงล า) อวยวะเพศเขาไปในชองคลอดของคนอน

ไมไดพยายามรวมเพศเลย............................................






4. ตลอด ( 4) สปดาหทผานมา ระหวางการรวมเพศ บอยแคไหนททานสามารถคงการ

แขงตวของอวยวะเพศอยได หลงจากทไดสอดใส (ลวงล า) เขาไปในชองคลอดของค

นอนแลว

ไมไดพยายามรวมทางเพศเลย............................................






5. ตลอด ( 4) สปดาหทผานมา ระหวางการรวมเพศ ยากแคไหน ทอวยวะเพศของทานคง

การแขงตวไวไดจนการรวมเพศสนสดลง

46

ไมไดพยายามรวมทางเพศเลย............................................






6. ตลอด (4) สปดาหทผานมา ทานไดเคยรวมเพศกครง

ไมไดพยายามรวมทางเพศเลย.....................................

พยายาม 1-2 ครง........................................................

พยายาม 3-4 ครง.......................................................

พยายาม 5-6 ครง.......................................................

พยายาม 7-10 ครง.....................................................

พยายาม 11 ครงขนไป...............................................

7. ตลอด ( 4) สปดาหทผานมา เมอทานไดรวมเพศ บอยครงแคไหนทมนไดผลเปนทพง

พอใจส าหรบทาน

ไมไดพยายามรวมทางเพศเลย........................................




47



8. ตลอด (4) สปดาหทผานมา ทานมความเพลดเพลนกบการรวมเพศแคไหน

ไมมการรวมเพศ........................................................

มความสขมากทสด...................................................

มความสขมาก...........................................................

มความสขพอสมควร................................................

แทบจะไมมความสข................................................

ไมมความสขเลย........................................................

9. ตลอด (4) สปดาหทผานมา เมอทานไดมการกระตนทางเพศหรอมการรวมเพศ ทานไดม

การหลงบอยแคไหน

ไมมการกระตนทางเพศหรอรวมเพศเลย...................






10. ตลอด (4) สปดาหทผานมา เมอทานมการกระตนทางเพศหรอมการรวมเพศทานรสกถง

จดสดยอด(รวมไปกบเกดการหลงหรอไมเกดการหลง)บอยครงแคไหน

48

ไมมการกระตนทางเพศหรอรวมเพศเลย.....................






11. ตลอด (4) สปดาหทผานมา ทานรสกมความตองการทางเพศ บอยครงแคไหน






12. ตลอด (4) สปดาหทผานมา ทานประเมนระดบความตองการทางเพศของทานอยางไร

สงมาก.......................................................................

สง.............................................................................

ปานกลาง..................... ............................................

ต า..............................................................................

ต ามากหรอไมมเลย...................................................

49

13. ตลอด ( 4) สปดาหทผานมา ทานมความพงพอใจกบการด ารงชวตทางเพศของทานโดย

สรปอยางไร

พงพอใจมาก.............................................................

พงพอใจปานกลาง....................................................

พงพอใจและไมพงพอใจเทาๆกน.............................

ไมพงพอใจปานกลาง...............................................

ไมพงพอใจมาก.........................................................

14. ตลอด ( 4) สปดาหทผานมา ทานมความพงพอใจในสมพนธภาพทางเพศกบคนอนของ

ทานอยางไร

พงพอใจมาก.............................................................

พงพอใจปานกลาง....................................................

พงพอใจและไมพงพอใจเทาๆกน.............................

ไมพงพอใจปานกลาง...............................................

ไมพงพอใจมาก.........................................................

15. ตลอด ( 4) สปดาหทผานมา ทานประเมนความมนใจในความสามารถทจะท าใหอวยวะ

เพศแขงตวและควบคมใหคงอยนานอยางไร

สงมาก.......................................................................

สง.............................................................................

ปานกลาง..................... ............................................

50

ต า..............................................................................

ต ามากหรอไมมเลย...................................................

51

Appendix 2

แบบทดสอบสมรรถภาพทางเพศของผชาย (Modified SHIM-IIEF5)

ID………….Initial………………ตอบ ณ วนท............เดอน.........................พ.ศ.......................

ค าถามตอไปน ถามเกยวกบผลตอการด ารงชวตทางเพศของทานทเกดเนองมาจากปญหา

การแขงตวของอวยวะเพศในชวง 4 สปดาหทผานมา

โปรดตอบค าถามอยางซอสตยและชดเจนเทาทจะท าได โปรดตอบทกค าถามโดยกา

เครองหมาย / ลงในชองสเหลยม ถาทานไมแนใจวาจะตอบอยางไรด โปรดใหค าตอบทดทสดท

ทานสามารถจะท าได

ค าจ ากดความ

การรวมเพศ หมายถง การลวงล าเขาไปในชองคลอดของคนอน

กจกรรมทางเพศ หมายถง การรวมเพศ การกอดจบประเลาประโลม การกระตนใหม

ความรสกทางเพศกอนรวมเพศและการส าเรจความใครดวยตวเอง

การหลง หมายถง การหลงน าอสจออกมาจากอวยวะเพศชาย(หรอม

ความรสกเสมอนม)

การปลกเราทางเพศ หมายถง การเลาโลมคนอนดวยการสมผสตามรางกายรวมทง

บรเวณอวยวะเพศ การดภาพกระตนความรสกทางเพศ ฯลฯ

52

1. เมอทานมเพศสมพนธ บอยครงแคไหนททานพงพอใจ พงพอใจทกครง หรอ เกอบทกครง.......................................

บอยครง(มากกวาครง)..........................................................

บางครง(ประมาณครงหนง)................................................

นานๆครง............................................................................

เกอบจะไมเลย.......................................................................

ไมมเพศสมพนธเลย.............................................................

2. ทานประเมนความมนใจในความสามารถของการคงการแขงตวของอวยวะเพศอยางไร สงมาก..................................................................................

สง.........................................................................................

ปานกลาง.............................................................................

ต า.........................................................................................

ต ามาก...................................................................................

3. เมอทานไดรบการเราทางเพศแลวอวยวะเพศแขงตวจนอวยวะเพศเขาชองคลอดไดบอยครงแคไหน ทกครง หรอ เกอบทกครง.....................................................


บางเวลา(ประมาณครงหนง)................................................

นานๆครง............................................................................

เกอบจะไมมเลย.......................................................................

53

ไมเคยมการเรา.....................................................................

4. เมอทานมเพศสมพนธ บอยครงแคไหนททานสามารถ คงการแขงตวของอวยวะเพศอยได หลงจากทสอดเขาไปในชองคลอดแลว ทกครง หรอ เกอบทกครง.....................................................


บางเวลา(ประมาณครงหนง)................................................

นานๆครง............................................................................

เกอบจะไมมเลยหรอไมมเลย................................................

ไมมเพศสมพนธเลย.............................................................

5. ขณะมเพศสมพนธ ยากแคไหนททานจะ คงการแขงตวของอวยวะเพศไวไดจนกวาจะม

การหลง

ไมยากเลย...............................................................................

ยากเลกนอย...........................................................................

ยากปานกลาง........................................................................

ยากมาก.................................................................................

ยากทสด................................................................................

ไมมเพศสมพนธเลย.............................................................

54

Appendix 3

แบบประเมนคณภาพชวต (SF-36)

ID……………………initial……………วนท............เดอน.........................พ.ศ...........

ค าถามเหลานจะถามเกยวกบสขภาพของทาน วาทานรสกอยางไรและสามารถท ากจกรรมตางๆตามปกตไดอยางไร ถาทานไมมนใจในการตอบค าถาม โปรดใหค าตอบทดทสดเทาททานเขาใจ

โปรดเลอกกาในชองทตรงกบความเหนของทาน เพยงหนงชองในแตละขอ

1. โดยทวไป ทผานมา 1 เดอนสขภาพของทานเปนอยางไร

ดเยยม ดมาก ด พอใช ไมดเลย

2. เปรยบเทยบชวง 1 ปทผานมา ปจจบนสขภาพของทานเปนอยางไร

ดขนมาก ดขนบาง เหมอนเดม แยลงบาง แยลงมาก

55

3. ภาวะสขภาพของทานในปจจบน มผลกระทบหรอเปนขอจ ากดในการประกอบ

กจกรรมตางๆเหลานหรอไม มากนอยเพยงใด

มผลมาก มบางเลกนอย ไมมผล

ก. กจกรรมทตองออกแรงมาก เชน วง ยกของหนกๆ เลนกฬาทใชแรงมาก...............................................................

ข. กจกรรมทออกแรงปานกลาง เชน ยายโตะ ถบาน..............................................................................................................

ค. ยกของ หรอหวตะกราจายตลาด....................................................................... ง. เดนขนบนไดหลายๆชน................................................................................. จ. เดนขนบนได 1 ชน....................................................................................... ฉ. กมตว หรอคกเขา หรอโคงตว......................................................................... ช. เดนทางระยะมากกวา 1 กโลเมตร................................................................ ซ. เดนทางหลายชวงเสาไฟฟา.......................................................................... ฌ. เดนทางมากกวา 30 เมตร หรอประมาณ

ครงทางระหวางเสาไฟฟา............................................................................. ญ. อาบน าและแตงตว........................................................................................ 4. ในชวงหนงเดอนทผานมา สขภาพรางกายของทาน มผลตอการท างานหรอ

กจวตรประจ าวนบางหรอไม ใช ไมใช ก. ท าใหตองลงเวลาในการท างานหรอกจกรรมลง................................ ข. ท างานไดนอยกวาทตงใจไว.............................................................. ค. ท างานหรอกจกรรมบางอยางไมไดอยางทเคย.................................... ง. มความยากล าบากในการท างานหรอกจกรรม

ตองใชความพยายามเพมมากขน.......................................................

56

5. ในชวงหนงเดอนทผานมา ปญหาทางอารมณ (เชนซมเศรา หรอวตกกงวล) มผลตอการท างานหรอกจวตรประจ าวนบางหรอไม ใช ไมใช ก. ท าใหลดเวลาในการท างานหรอกจกรรมลง...................................... ข. ท างานไดนอยกวาทตงใจไว.............................................................. ค. ขาดความรอบคอบในการท างานหรอกจกรรม

เหมอนอยางทเคยท าได...................................................................... 6. ในชวง 1 เดอนทผานมาปญหาสขภาพกายหรอปญหาทางอารมณ รบกวน

ความสมพนธของทานกบครอบครว เพอนฝงหรอเพอนบานบางหรอไมอยางไร

ไมเลย เพยงเลกนอย ปานกลาง คอนขางมาก มาก

7. ในชวง 1 เดอนทผานมาทานมอาการเจบปวดตามรางกายหรอไม

ไมมเลย เพยงเลกนอย ปานกลาง รนแรง รนแรงมาก

8. ในชวง 1 เดอนทผานมา อาการปวดรบกวนการท างานตามปกตของทานหรอไม

ไมเลย เพยงเลกนอย ปานกลาง คอนขางมาก มาก

57

9. ในระยะ 1 เดอนทผานมา ทานมความรสกตอไปนบอยครงเพยงใด ตลอด เวลา

เกอบตลอด เวลา

บอยๆ บางเวลา

นานๆครง

ไมมเลย

ก. รสกสดชนมชวตชวา.................................................................................. ข. ประสาทเครยด................................................................................................ ค. หดหจนไมมอะไรท าให

สดชนขนได............................................................................................... ง. สงบและเปนสข......................................................................................... จ. มพลงมาก.................................................................................................. ฉ. ทอแท หอเหยว.......................................................................................... ช. รสกหมดเรยวแรง...................................................................................... ซ. รสกมความสข........................................................................................... ฌ. รสกเหนอยลา...........................................................................................

10. ในชวง 1 เดอนทผานมา ปญหาทางกายและจตใจ ท าใหรบกวนตอการเขาสงคม

การพบปะเพอนฝงและญาตสนทของทานอยางไรบาง

ตลอดเวลา เกอบตลอดเวลา บางเวลา นานๆครง ไมรบกวน

58

11. ขอความตอไปน เปนจรงส าหรบทานหรอไม จรงทสด

จรง ไมร ไมคอยจรง

ไมจรงเลย

ก. ฉนไมสบายงายกวาคนอน............................................................... ข. ฉนมสขภาพดพอๆ กบคนอน ทฉนรจก.......................................................................................... ค. ฉนคาดวาสขภาพของฉน

จะแยลง............................................................................................. ง. สขภาพของฉนดเลศ.........................................................................

ขอขอบคณททานไดกรณาตอบแบบสอบถามน

andrographis periculata ness

Documents

organic erectile dysfunction

endothelial dysfunction

oral therapy

data presentation

research methodology

data layout

outcome data collection

data collection form