NATIONAL ATAXIA REGISTRY AND NATURAL HISTORY STUDY

S H Subramony M.D.Professor of NeurologyMcKnight Brain Institute and University of Florida College of MedicineGainesville, FL

DISEASE REGISTRIES

Special database containing information about persons with specific diseases

Data is systematically collected and standardized Data entry

Patients Physicians and health care providers Researchers EMR’s

Usefulness Promote research Easier patient recruitment for studies and trials Genotype/phenotype information Link repositories and other data resources Therapy effectiveness Knowledge dissemination

NATIONAL ATAXIA REGISTRY

Database that collects basic information on patients with “degenerative” ataxia

“Contact” registry: contact information and diagnosis

“Curated”: we confirm the diagnosis as much as possible

What type of patients can participate? Patients with ataxia not caused by an obvious and

known disease like MS, strokes, tumors, infections etc Patients with inherited and sporadic ataxias of all types You don’t have to need a definite diagnosis of cause,

only that you have ataxia

PURPOSE OF NAR

Facilitate clinical research including drug trials in the field of ataxias

Bring appropriate research groups in touch with the right group of patients

Caveats Registry participation does not

guarantee participation in a drug trial You do not commit to participation in any

trial or study

ELIGIBLE SUBJECTS

Inherited ataxias Dominant (SCA 1,2,3,5,6,7,8,10,12,13,14,17,DRPLA,

other uncertain types) Recessive (FA, AOA, POLG/MIRAS, AT, other types) Mitochondrial, X-linked including FXTAS

Sporadic ataxia (MSA, OPCA, idiopathic ataxia) Congenital ataxia Any other degenerative ataxias including gluten

ataxia, GAD ataxia Subjects at risk for inherited ataxias(usually

dominant) All inclusive

REGISTRY PROCESS

Visit the web site (directly or through the NAF web site) www.nationalataxiaregistry.org

Click on new user log in on home page Enter essential contact information on page 2 Enter and confirm e mail address, choose a

password and a security question on page 3 Print informed consent from page 4 Coordinator will contact you for telephonic consent

before activating the account Once activated you will be able to log back and

enter diagnostic details and basic information on “functional stage”

KEEP PASSWORD WRITTEN IN SECURE PLACESEND COPY OF KEY DIAGNOSTIC DOCUMENT

WITH CONSENT

NAR 2012

1154 subjects have provided initial contact information

343 subjects have completed consent and submitted diagnostic information

SCA 1

SCA 3

SCA 6 FA

AOA 1

SCA U

nk0

20406080

100120

NUMBER OF SUBJECTS WITH DIFFERENT DIAGNOSES

SCA1

SCA2

SCA3

SCA5

SCA6

SCA8 FA

Sporad

icAO

A 1AO

A 2

SCA Unk

.Othe

r0%

20%

40%

60%

80%

100%

120%

MaleFemale

SCA1

SCA3

SCA6 FA

AOA 1

SCA Unk

.0%

20%

40%

60%

80%

100%

120%

Less than 20 yrs20-50 yrsMore than 50 yrs

Gender ratios

Current age

SCA1

SCA2

SCA3

SCA5

SCA6

SCA8 FA

Sporad

icAO

A 1AO

A 2

SCA Unk

Other

0%10%20%30%40%50%60%70%80%90%

100%

Less than 20 yrs20-50 yrsMore than 50 yrsNot listed

SCA1

SCA2

SCA3

SCA5

SCA6

SCA8 FA

Sporad

icALA

1ALA

2

SCA Unk

.Othe

r0%

10%20%30%40%50%60%70%80%

00.511.522.533.544.555.56not list.

Age at onset

Functional stage

OBSTACLES AND COMING CHANGES

Two step process, IRB mandated Need for telephonic consent with each

individual, return of singed paper consent Volunteer soft ware consultants E mail username Multiple diagnoses New ongoing initiatives

Back up compensated consultant Negotiation with UF IRB for approving web based

consent Other necessary amendments to the protocol

THE CLINICAL RESEARCH CONSORTIUM FOR SPINOCEREBELLAR ATAXIA

The CRC-SCA includes all the centers participating in the NIH funded natural history study of SCA 1,2,3 and 6 and all are members of the CAG

The aim of this study is to collect information on US patients with SCA 1,2,3, and 6 regarding the natural progression of the disease, identify the best methods to assess disease progression and find any genetic markers that may influence the characteristics of the disease

PARTICIPATING SITES

NATURAL HISTORY DATABASE Natural History Database is important for

understanding the disease progression, which will be critical in designing most clinical trials.

Only individuals with the diagnosis of SCA1, 2, 3 and 6 are included in the Natural History Database.

Visits occur every 6 month. Each visit involves an interview, a physical

examination, timed-measurement such as 25 meter (8 ft) walk and 9-hole peg board testing.

The first/baseline visit is used to consent the patient Blood is drawn once and tested for DNA modifiers at

University of Utah lab. A subset of patients will undergo home-based ataxia

testing (gait monitor and computer on-line click test).

National Ataxia Registry

NAF/UCLA Natural History Database

DMCCNatural History Database

Utah Genetic Modifier

Database

DMCC Genetic Modifier

Database

RDCRN WebsiteCRC-SCA Investigators

SCA1,2,3&6

Ataxia patients

Clinical data collectionBlood samples

NATURAL HISTORY STUDY

0

50

100

150

200

250Fe-maleMaleTotal

Columns 1-6: American Indian, Asian, Pacific Islander, African American, White and other

AGE AT REGISTRATION AND DURATION OF DISEASE

SCA 1 SCA 2 SCA 3 SCA 60

1020304050607080

SCA 1 SCA 2 SCA 3 SCA 605

10152025

NUMBER OF SUBECTS AND MEAN AGE AT ONSET

SCA 1 SCA 2 SCA 3 SCA 60

20

40

60

80

100

120

140

Number of subjects

Mean age at onsetSCA 1 SCA 2 SCA 3 SCA 6

0

10

20

30

40

50

60

70

SARA T25W 9HP

01020304050607080

SCA 1SCA 2

SCA 3 SCA 6

SCA 1 SCA 2 SCA 3 SCA 6012345

MEAN SCORES AT BASELINE VISIT

SARA, walk test, peg board test

Functional stage

SAMPLE SIZE ESTIMATES

Number needed per arm to detect 50% reduction in disease progression in 1 year: 143 for 9HPT, 250 for SARA and 275 for SCAFI

Obs TYPE CHG18CON CHG18LIT P_REDUCTION Alpha Power NTotal1 One-arm efficacy 3.3 2.31 30 0.0492 0.806 66

2 One-arm efficacy 3.3 1.98 40 0.0492 0.806 38

3 One-arm efficacy 3.3 1.65 50 0.0492 0.805 25

4 Two-arm efficacy 3.3 2.31 30 0.0492 0.803 256

5 Two-arm efficacy 3.3 1.98 40 0.0492 0.800 144

6 Two-arm efficacy 3.3 1.65 50 0.0492 0.805 94

SUMMARY

NAR has continued to accrue subjects Substantial number of subjects have no

definite causative diagnosis Issue of informed consent is a difficult

one CRC-SCA

Has generated substantial natural history data

Sample size estimates still disappointingly large

International collaboration may be needed and is being initiated

AKNOWLEDGEMENTS

Becca Beaulieu Tommy Zhu Sue Hagen Bill Hartnett Marty Ohmann Tee Ashizawa CRC- consortium investigators