treating neuropathic pain

Relieving Neuropathic Pain A study to develop an understanding of the most effective use of the NMSIII in the relief of intractable chronic neuropathic pain. Initial studies have shown that the NMSIII is highly effective in providing relief from neuropathic pain that has failed to respond to other treatments. This paper outlines the background to the study, the data required to develop an in‐depth understanding of the most effective way to utilize the NMSIII and the procedures to be adopted by the clinicians assisting in the gathering of data. MF Medical Ltd 20 June 2010

21 June 2010

INTRODUCTION

This study is designed to develop a better understanding of the use of external

neuromodulation for the relief of intractable localised chronic neuropathic pain and to

develop treatment protocols and regimes.

A small study was carried out by Guy’s & St Thomas’ Hospital in 2003 using the Neuro Trace

III. It was observed that the pain relief produced was dramatic and had, at least, a medium

term effect.

Since this study, the device, a NeuroTrace III produced by Xavant, has been used to provide

relief to a large number of sufferers. To date however there has been no detailed study to

examine the most effective means of employing the technique, nor which patients are most

suitable.

The NeuroTrace III was designed for regional anaesthesia both nerve mapping

(transcutaneous stimulation) as well as stimulation of the nerve using an insulated nerve

block needle (percutaneous). Xavant have since produced a simpler device, the NMSIII

designed solely for transcutaneous nerve stimulation, eliminating much of the electronic

programming required in the original device but retaining the same transcutaneous

stimulating capabilities. The type of stimulation should not be confused with that delivered

by the standard TENS device

There are many variables that potentially affect the overall performance of the technique

and these have as yet not been analysed.

The purpose of this study is to develop a better understanding of those variables and to

validate the findings of the original study by Guy’s and St Thomas’.

BACKGROUND

Following the study in 2003 it became clear that short external low frequency stimulation either targeted at the site of the maximum pain or deeper afferent sensory nerves in patients with intractable pain provides significant pain relief.

In that study 35 patients underwent stimulation at a frequency of 2Hz with a current of between 1mA and 15mA either directly over the affected area or to the nerve path supplying the area for a period of 5 minutes.

The results were as follows

No. of patients Decrease in VAS at completion

19 100 %

4 90%

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4 63%

4 50%

1 25%

1 20%

1 15%

While the results are clearly of great statistical significance the study was too small to derive

any data that could be of statistical significance in the detailed analysis of such variables as

pain site, current amplitude improvements from different Vas starting points, skin type etc.

With the development of a new device that can be made much more widely available it is

clearly important to collect the data that will make such an evaluation possible.

OBJECTIVES

There are two main objectives of this study:

Validation of the conclusions drawn and implied by the study at St Thomas Hospital

on the effectiveness of external neuromodulation using the NMS III on providing

relief from neuropathic pain

To gather statistical data in order to develop protocols and treatment regimes for

the alleviation of chronic intractable neuropathic pain.

There is also a secondary objective:

Identify further evidence of the effects noted by the original study and subsequently of restoring motor function in patients.

RATIONALE FOR THESE OBJECTIVES

The original study provides very clear and statistically significant evidence that external

neuromodulation using the Neuro Trace 111 at low frequency can be very effective at

alleviating neuropathic pain very rapidly. However, the study was small and the range of

initial Vas scores (>5) was such that it is difficult to draw conclusions on the absolute effect

of the technique.

There are a large number of parameters involved, many of which may be interrelated. It is

important to identify the effects of the individual parameters and their relationships.

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For example, we believe that the level of current may have a bearing on the outcomes. The

selection of the level of current delivered is determined by the level of current with which

the subject is reasonably comfortable. However this is itself is determined by two factors:

The body’s own resistance to the current – a consequence of skin resistance and

the nature of the tissue in the area to which the current is applied. Since the device

is designed to deliver current at the rate set on the device it automatically increases

the voltage to overcome the resistance, which clearly affects the total power

delivered.

The patient’s psychological reaction to the stimulus also has a bearing. We know

that some people may tolerate a very high current – up to 20mA – and even find it

to be a mildly pleasant sensation, while others find even a very small current – less

than 3mA – sufficiently unpleasant to be unable to continue.

The consequence is that one patient may for example tolerate only a low current but may be

experiencing a significantly higher level of total power than another who receives a

significantly higher current treatment.

While in each case in the original study some relief was provided we do not know the

duration of the relief. Based on subsequent anecdotal evidence we know that in some, the

period of relief was for several weeks (beyond the duration of the original study and the

subsequent anecdotal evidence) while in other cases the period of relief was of much

shorter duration and began to decline within a few days.

The study has therefore been designed to shed further light on this set of variables.

DESIGN

The study is designed to assess both the immediate effect of the technique and the effect of

a series of treatments in providing pain relief.

OVERVIEW

After taking a history of the subject’s experience of pain, a VAS assessment and their

experience of the impact of the pain on their life quality, each participant will receive a five

minute treatment of peripheral neuromodulation at 2Hz with a current of between 5 and

15mA.

Following that treatment the patient will complete a further VAS assessment.

Seven days later the subject will return for a further treatment. Prior to that treatment a

further VAS assessment will be completed and if the patient reports a significant return of

the pain over the period they will be invited to undergo twice weekly treatments for a

further period of two and a half weeks. Those who have not experienced a significant

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recurrence of pain will be given two further treatments, one on this visit and one a further

week later.

A VAS score will be taken both before and after each treatment.

One week after the final treatment a further VAS score and Pain Impact assessment will be

carried out.

On completion of the final assessment all subjects will be invited to register on the website

set up to manage the test data and contribute their experiences and to provide their contact

details for further follow up.

Those who are not pain free but are enjoying significant relief as a result of regular

treatments will be invited to re‐attend for further palliative treatments.

DATA

The following data will be collected for analysis

ABOUT THE PERSON

Age Gender Ethnic Origin

Level of fitness Height Weight

Diabetes Other conditions General Physical Fitness

ABOUT THE PAIN

Date of onset Clinical diagnosis of cause –

if any

Possible Cause

Site of pain Nature of Pain Interference with physical

activity

VAS DN4 Pain Impact

Treatments Tried Dates Duration

Results

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TREATMENT

ON FIRST TREATMENT

Instrument Setting Current Frequency

Program Position of probe Pain site

Path Distance Located on Diagram

Duration of Treatment Vas Score After Comments ‐ Clinician/patient

AT SUBSEQUENT TREATMENTS

Time since last treatment Date at which the pain level

rose significantly

Pain Impact

Instrument Setting Current Frequency

Program Position of probe Pain site

Path Distance Located on Diagram

Duration of Treatment VAS

PROCEDURES

BACKGROUND

This Study is designed to explore a number of aspects of the effect of external

neuromodulation. We know that with this device different patients enjoy different lengths

of relief from pain. We wish to identify how long this period is and the parameters that

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affect and influence the period. We are also aware that patients suffering a reasonable

period of relief from pain will frequently revert to normal patterns of action which in turn

removes the cause of the pain.

We wish to ensure that we acquire data on both these effects and therefore an assessment

will be made 7 days after the first treatment. This assessment will be determine whether

further treatments continue to be given weekly or are increased to twice per week.

INTRODUCTION

This section covers procedures at:

Initial treatment

Prior to second treatment

Subsequent treatments

At conclusion of treatments

Ideally the data collection forms should be completed electronically and submitted by email,

but where this is not possible manual copies of the forms are also provided.

Instructions for completion of the electronic forms accompany the forms themselves which

can be downloaded from www.mfmedical.co.uk. (Please note that these are not yet

available.)

INITIAL TREATMENT

Once a potential subject has been identified they should be screened to ensure that they

match the criteria outlined above and contained on the first page of the data forms. Please

complete this

The patient should be asked to read the Patient Information Sheet and then sign the Patient

Consent Form.

The patient should then be asked to complete the VAS and Pain Impact Questionnaire in that

order.

You should then complete the DN4 Questionnaire with the patient.

Take a history from the patient based on the Initial Treatment Form and complete the form

(preferably the on line version).

Carry out the treatment with the device delivering a current at as high a current as the

patient can reasonably tolerate at a frequency of 2Hz for a period of 5 minutes. The patient

should be comfortable with a current between 8mA and 15mA. If the patient cannot

tolerate a current of above 5mA you should end the treatment.

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The precise mechanics of the treatment are discussed below.

At the end of the treatment the patient should complete a second VAS after 5 minutes and a

third after 10 minutes and the Initial Treatment Forms should be completed and submitted

to MF Medical.

SECOND TREATMENT

Before commencing the second treatment it is important to determine whether subsequent

treatments should be twice weekly or weekly.

Get the patient to complete another VAS. If the patient has seen a significant rise in pain

since the completion of the first treatment it will be important to establish at what point the

patient felt the degree of pain started to interfere with their normal performance.

Once the decision on the frequency of treatments has been made you can proceed to treat

the patient for the second time.

On completion of the second treatment get the patient to complete a second VAS, complete

Form 2 and submit it to MF Medical.

SUBSEQUENT TREATMENTS

Subsequent treatments should be conducted in the same manner as the second treatment

except that no decision has to be made about the frequency of treatment.

A patient on a weekly treatment scheme should have one further treatment (total of three

treatments); a patient on a twice weekly scheme should have three further treatments total

of five treatments) which should provide a minimum of two and a half weeks with a

substantial reduction of pain.

PARTICIPANTS

Subjects will be enlisted according to the following criteria:

1. Patient age is 18 years or older, either sex

2. Patient has chronic neuropathic (or predominantly neuropathic) intractable pain

3. Patient has an area of pain with a typical dermatomal distribution that can be

expected to be covered with a single episode of local stimulation

4. Patient has a Visual Analogue Scale (VAS) pain score of 5 cm (or greater) on a 10 cm

line

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Exclusion criteria

1. Patient has a history of substance abuse or substance dependency in the past 6

months prior to baseline data collection

2. Patient is currently participating in another clinical study

3. Patient lacks capacity for informed consent to the trial in the view of person taking

consent and/or investigators

4. Pregnancy

5. Patient has difficulties in adequate understanding of English for consent, clinical

review and self‐completion questionnaires

6. Patient does not permit notification to General Practitioner of enrolment in the

study

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7. Patient has previous experience of peripheral neuromodulation. Note that prior

transcutaneous electrical nerve stimulation (TENS) experience is permitted.

8. The source of the pain is Trigeminal neuralgia or similar. Do not treat facial pain.

STATISTICAL PLAN

So little is currently known about the results – other than the phenomenal immediate effects

– that the intention is to carry out an initial review of the data to establish the main

correlations and effects. This will be done once there is data from 50 initial treatments once

the data gathered at the second treatment session is available.

The initial statistics that appear important are:

1. Degree of initial pain – level of pain after treatment and related to:

a. Initial degree of pain

b. Site of pain

c. Diagnosis of cause of pain

d. Current used in treatment

2. Duration of relief – overall and related to

a. Initial degree of pain

b. Site of pain

c. Diagnosis of cause of pain

d. Current used in treatment

At this time we will review the data and consider whether any modifications may be

appropriate.

Once all the data is available it will be examined to establish correlations

DATA HANDLING AND SECURITY

Data will be recorded on datasheets held by the clinician. Subjects will be identified by a

reference number and the data relayed to us using that reference number. The clinician will

maintain a register that cross references the number to the patient’s name.

No data will be passed to MF Medical that can personally identify the subject.

On the completion of the study patients will be invited to register at a website where they

can add their comments and experiences. Registration at that website will require a “double

sign up”.

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APPENDICES

A Patient Information sheet

B Consent Form

C Data collection sheets

D Patient identification register

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PATIENT INFORMATION

Thank you for reading this and, we hope, taking part in this study.

We are trying to understand why certain types of pain respond so well to the electrical

stimulation provided by NMSIII used by anaesthetists.

This type of device has been widely used for many years to help anaesthetists identify

precisely where a nerve runs through the body. It was discovered that one side effect of

using the device was the immediate relief of pain.

A study was then carried out on thirty five people in a leading NHS hospital in London to see

how effective it was. More than half (19) showed almost total relief of pain in the short to

medium term; four reported a 90% reduction and another twelve received at least 50%

reduction. The remaining three had at least some pain relief.

The NMSIII has continued to be used by anaesthetists, pain clinics and physiotherapists to

treat patients suffering from certain types of pain. It delivers a very low current (measured in

milliamps) powered by a standard radio type battery to stimulate the nerves.

We now wish to understand more clearly the most effective way of using this approach.

To help us do this we need to gather much more information about your condition, the

precise treatment regime and its effect.

The information gathered by the Doctor or Physiotherapist who treats you will be

completely confidential. Because it is confidential it will be passed to MF Medical in a way

that prevents MF Medical from identifying you. At the end of your treatment your clinician

may ask if MF Medical may contact you and identify your data. You are under no obligation

to consent to this and we will respect your decision. In the event that you do consent to such

contact MF Medical undertake not to disclose your information.

You do not have to take part in this study but if you do the information gained could go a

long way to helping others suffering a similar complaint.

THE TREATMENT

You will receive between 3 and 5 treatments in total. Treatments will be weekly or twice

weekly depending on the result of the first treatment.

At each treatment either the site of the pain or the nerve supplying the site of the pain will

be stimulated with a small electric current by placing a sticky electric pad near to the site

and then directing the current towards the affected nerve or area of pain using a hand held

probe.

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The device will deliver two pulses of electricity per second. Your clinician will start this at a

very low level, probably less than you will be able to detect. They will gradually increase the

power until you can feel a distinct twitching sensation.

Some find this mildly pleasant while other people begin to find it unpleasant. Ideally you

should receive the maximum power you feel acceptable.

Once this power level has been identified the treatment will continue for five minutes.

Should you find the sensation becoming uncomfortable during this period tell the clinician

and they will reduce the power.

If for some reason you decide the sensation is not acceptable tell the clinician and they will

end the treatment.

THANK YOU

First we hope that you gain significant pain relief from your treatments.

We also hope that by collecting and analysing the data provided by this study we will be able to develop very clear protocols to help clinicians apply the best treatment for a wide variety of patients and conditions. While the results of the study may not deliver immediate benefits to you personally we hope that the close attention you are receiving ensures the best possible outcome.

We also understand how unpleasant the effects of intractable pain are, not least because one of the partners in MF Medical suffers from it to a limited degree. We hope, together, we can make a difference.

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CONSENT FORM

Patient Identification Number for this trial:

CONSENT FORM FOR RESEARCH STUDY

TITLE OF PROJECT: Data collection to assess the most effective way to the use of external neuromodulation for

the relief of intractable localised chronic neuropathic pain

Name of Researcher:

Please tick

to confirm

I confirm that I have read and understand the information sheet dated 21 June 2010 for the

above study.

I have had the opportunity to consider the information, ask questions and have had these

answered satisfactorily.

I understand that my participation is voluntary and that I am free to withdraw at any time,

without giving any reason, without my medical care or legal rights being affected.

I understand that relevant sections of any of my medical notes and data collected during the

study, may be looked at by responsible individuals from [company name], from regulatory

authorities or from the NHS Trust, where it is relevant to my taking part in this research. I give

permission for these individuals to have access to my records.

I agree to my GP being informed of my participation in the study.

I agree to take part in the above research study.

__________________________

Name of Patient

______________

Date

__________________________

Signature

__________________________

Name of Person taking consent

(if different from researcher)

______________

Date

__________________________

Signature

__________________________

Researcher

______________

Date

__________________________

Signature

When complete, 1 copy for patient: 1 copy for researcher site file: 1 (original) to be kept in medical

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notes.

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DATA COLLECTION SHEETS

First Session

Initial Patient Assessment

Treatment Information

Post Treatment

Second Session

Pre‐treatment Review


Post Treatment

Subsequent Sessions

Pre‐treatment Review


Post Treatment

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FIRST SESSION

Pre‐Treatment Patient Reference No:

Date:

1. Mark the areas on your body where you feel the symptoms. (Please use the appropriate symbol.

Mark areas of radiation. Include all affected areas.)

2. Indicate the degree of pain by marking on the scale below:

3. What medication and dosage did you take during the last week?

4. Circle the number that describes how, during the last week, pain has affected you:

Does not Interfere

Completely Interferes

General Activities 0 1 2 3 4 5 6 7 8

9 10

Mood 0 1 2 3 4 5 6 7 8

9 10

Walking Ability 0 1 2 3 4 5 6 7 8

9 10

Numbness N

Pressure P

Burning B

Pins & Needles PN

Stabbing/Aching SA

Other O

Specify other

No Pain Worst Pain Possible

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Work (inc Housework) 0 1 2 3 4 5 6 7 8

9 10

Relations with others 0 1 2 3 4 5 6 7 8

9 10

Sleep 0 1 2 3 4 5 6 7 8

9 10

Enjoyment of life 0 1 2 3 4 5 6 7 8

9 10

Ability to concentrate 0 1 2 3 4 5 6 7 8

9 10

Appetite 0 1 2 3 4 5 6 7 8

9 10

DN4 QUESTIONNAIRE

Please answer yes or no to the following questions.

Interview of the Patient

1. Does the pain have one or more of the following characteristics?

Yes No

Burning

Painful cold

Electric Shocks

2. Is the pain associated with one or more of the following symptoms in the same area?

Tingling

Pins and needles

Numbness

Itching

Examination of the patient

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3. Is the pain located in an area where physical examination may reveal one or more of the

following characteristics?

Hypoesthesia to touch

Hypoesthesia to pin prick

4. In the painful area can the pain be increased by?

Brushing

Score

Yes = 1 No = 0 Total = …../10

PATIENT INFORMATION

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21 June 2010

TREATMENT

Current: Frequency: Pulse Width:

Position of Probe: Position of Electrode: Separation (cms)

Position of Probe: Electrode: (Please also show on diagram)

Treatment on: () Pain Site Nerve Path

Duration of Treatment: VAS after treatment:

Comments

Positions

Electrode ‐

Probe ‐

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AFTER TREATMENT – 5 MINUTES

Please indicate the degree of pain by marking on the scale below:

Patient Comments


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Patient Comments


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SUBSEQUENT SESSIONS

Pre‐Treatment Patient Reference No: Treatment No:

Date:

1. Mark the areas on your body where you feel the symptoms. (Please use the appropriate symbol.

Mark areas of radiation. Include all affected areas.)

2. Indicate the degree of pain by marking on the scale below:

3. What medication and dosage did you take during the last week?

4. Circle the number that describes how, during the last week, pain has affected you:

Does not Interfere

Completely Interferes

General Activities 0 1 2 3 4 5 6 7 8

9 10

Mood 0 1 2 3 4 5 6 7 8

9 10

Walking Ability 0 1 2 3 4 5 6 7 8

9 10

Numbness N

Pressure P

Burning B

Pins & Needles PN

Stabbing/Aching SA

Other O

Specify other


21 June 2010

Work (inc Housework) 0 1 2 3 4 5 6 7 8

9 10

Relations with others 0 1 2 3 4 5 6 7 8

9 10

Sleep 0 1 2 3 4 5 6 7 8

9 10

Enjoyment of life 0 1 2 3 4 5 6 7 8

9 10

Ability to concentrate 0 1 2 3 4 5 6 7 8

9 10

Appetite 0 1 2 3 4 5 6 7 8

9 10

TREATMENT

Current: Frequency: Pulse Width:

Position of Probe: Position of Electrode: Separation (cms)

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Position of Probe: Electrode: (Please also show on diagram)

Treatment on: () Pain Site Nerve Path

Duration of Treatment: VAS after treatment:

Comments

Positions

Electrode ‐

Probe ‐

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AFTER TREATMENT – AFTER 5 MINUTES


Patient Comments


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Patient Comments


21 June 2010

IDENTITY REGISTER

Name Reference No

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

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IDENTITY REGISTER – CONTINUED (16 – 30)

Name Reference No

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

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IDENTITY REGISTER – CONTINUED (31‐45)

Name Reference No

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

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treating neuropathic pain

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