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S H Subramony M.D. Professor of Neurology McKnight Brain Institute and University of Florida College of Medicine Gainesville, FL. NATIONAL ATAXIA REGISTRY AND NATURAL HISTORY STUDY. DISEASE REGISTRIES. Special database containing information about persons with specific diseases - PowerPoint PPT Presentation
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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