Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias

July 30, 2026 updated by: Lauren Moore

Clinical Research Consortium for the Study of Cerebellar Ataxias (CRC-SCA) for the Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias (SCA)

Spinocerebellar ataxias (SCA) are genetic neurological diseases that cause imbalance, poor coordination, and speech difficulties. There are different kinds of SCAs and this study will focus on types 1, 2, 3, 6, 7, 8, 10, 27B, and RFC1-ataxia (SCA 1, SCA 2, SCA 3, also known as Machado-Joseph disease, SCA 6, SCA 7, SCA 8, SCA 10, SCA27B, and RFC1-ataxia, also known as CANVAS). The diseases are rare, slowly progressive, cause increasingly severe neurological difficulties, and are variable across and within genotypes. The purpose of this research study is to bring together a group of experts in the field of SCA for the purpose of learning more about the disease.

The research questions are:

  1. How do these diseases progress over time?
  2. What are the best ways to measure the progression?
  3. Do some genes, other than the gene that is abnormal in these diseases, have any effect on the way the disease behaves?

This is a nationwide study and the investigators expect that 1400 patients will participate all over North America. The participants will remain in the study for an indeterminate period of time, for as long as they are willing to participate. Study visits will be done every 12 months.

Within the broader CRC-SCA, there is an Imaging Sub-study aiming to identify magnetic resonance imaging (MRI) markers sensitive to the onset and progression of common SCAs. To accomplish this, participants attend annual visits involving a neurological exam, surveys, a blood draw, and an MRI scan. Participants can attend visits at one of three US locations - Minneapolis, MN; Gainesville, FL; or Dallas, TX and two European locations - Paris, France and Bonn, Germany. Eligible participants must either have SCA1, 2, or 3 or have been a participant of the previous READISCA study (NCT03487367). Gene-positive participants must have a SARA score less than 10; however, there is no SARA limit for participants previously enrolled in READISCA. All participants must be 18 years or older. Gene-negative participants should be 25-65 years old.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Study participants will have 2 teaspoons (10 milliliters) of blood collected during the first/screening visit in order to extract DNA. The sample will be sent to the University of Chicago Genetics Laboratory for the study of genetic factors that modify the course of the disease.

Participants will be asked to return for visits on an annual basis. As part of this study, whole blood samples will be collected from participants at each visit and deposited into a tissue repository called BioSEND (NINDS biomarker repository housed at Indiana University). Sample submissions to the repository may give scientists valuable research material that can help develop new diagnostic tests, new treatments, and new ways to prevent diseases. Scientists will not use participant samples, or material isolated from it, for commercial products or services.

CSF collection is an optional part of this study for SCA participants aged 18 years or older. If a participant declines the CSF collection, the participant will be allowed to continue with participation in the remainder of the study.

Participant samples will not have the participant's name or other personal information linked to it. Samples may be shared with researchers at other institutions. The only information the researchers will keep with the sample is participant age, disease type, the age at onset of disease, and the duration of the disease. The principal investigator at a participant's study site will be the only person who can link the sample to a participant. Participants can have their samples removed from the bank later by written request to their principal investigator.

At each annual visit, study participants will also be asked to complete several assessments that include questionnaires, motor function tests, a cognitive assessment, a neurological exam, and an MRI scan if enrolled in the MRI Sub-study.

Study Type

Observational

Enrollment (Estimated)

1400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, 30153
        • Recruiting
        • Le Centre hospitalier de l'Université de Montréal
        • Principal Investigator:
          • Antoine Duquette, MD
        • Contact:
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California Los Angeles
        • Principal Investigator:
          • Susan Perlman, M.D.
        • Contact:
      • San Francisco, California, United States, 94115
        • Recruiting
        • University of California San Francisco
        • Principal Investigator:
          • Michael Geschwind, MD
        • Contact:
        • Sub-Investigator:
          • Cameron Dietiker, MD
    • Florida
      • Gainesville, Florida, United States, 32610
        • Recruiting
        • University of Florida
        • Principal Investigator:
          • S H Subramony, MD
        • Contact:
        • Principal Investigator:
          • Matthew Burns, MD, PhD
      • Tampa, Florida, United States, 33620
        • Recruiting
        • University of South Florida
        • Contact:
        • Principal Investigator:
          • Theresa Zesiewicz, M.D.
    • Georgia
      • Atlanta, Georgia, United States, 30320
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Withdrawn
        • University of Chicago
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Nortwestern University
        • Contact:
        • Principal Investigator:
          • Puneet Opal, MD
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • John Hopkins University
        • Principal Investigator:
          • Chiadi Onyike, MD, MHS
        • Contact:
        • Principal Investigator:
          • Liana Rosenthal, MD, PhD
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Harvard University
        • Contact:
        • Principal Investigator:
          • Jeremy Schmahmann, M.D.
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Contact:
        • Principal Investigator:
          • Henry Paulson, M.D., PhD.
        • Principal Investigator:
          • Sharan Srinivasan, M.D.
        • Sub-Investigator:
          • Peter Todd, MD, PhD
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Active, not recruiting
        • University of Minnesota
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University
        • Contact:
        • Principal Investigator:
          • Sheng-Han Kuo, M.D.
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • University of Texas Southwestern Medical Center
        • Contact:
        • Principal Investigator:
          • Vikram Shakkottai, MD, PhD
      • Houston, Texas, United States, 77030
    • Washington
      • Seattle, Washington, United States, 98195
        • Recruiting
        • University of Washington
        • Contact:
        • Principal Investigator:
          • Marie Davis, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Participants will be recruited broadly across the United States and Canada through various means, including outpatient clinics, word-of-mouth referrals, and announcements/emails via the National Ataxia Foundation. Participants must complete annual research visits at one of the 16 designated CRC-SCA research sites with the corresponding study site Principal Investigator or Sub-Investigator.

For MRI Sub-study only: Select participants may be recruited in Paris, France and in Bonn, Germany to participate locally in Europe in the MRI Sub-study with the corresponding study Investigators and teams.

Description

Inclusion Criteria:

  • Affected individuals aged 6 or above with symptoms and/or signs of ataxia with genetic confirmation of SCA 1, 2, 3, 6, 7, 8, 10, 27B, or RFC1-ataxia either in themselves or first degree family member.
  • Any individual aged 18 or above with a definite molecular diagnosis of SCA 1, 2, 3, 6, 7, 8, 10, 27B, or RFC1-ataxia.
  • Former participants of the READISCA (NCT03487367) study.
  • Willingness to participate in the study and ability to give informed consent
  • For MRI Sub-Study only: Previous READISCA enrollees; individuals aged 18 or above with a genetic confirmation of SCA1, 2, or 3 and a SARA score <10 at MRI pre-screening; Healthy control participants without neurological condition.

Exclusion Criteria:

  • Exclusion of SCA 1, 2, 3, 6, 7, 8, 10, 27B, or RFC1-ataxia by previous DNA testing.
  • A lack of willingness to participate in the study
  • For MRI Sub-study only: Inability to undergo MRI scanning, pregnancy, and other neurological diseases than those of interest.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Participants with Spinocerebellar Ataxias (Main Study)
Individuals aged 6 or older with the spinocerebellar ataxias 1, 2, 3, 6, 7, 8, 10, 27b, or RFC1-Ataxia will be enrolled for genetic testing, blood collection, assessments, and questionnaires.
Genetic: Genetic Testing
About two teaspoons (10 milliliters) of blood will be collected during the first/screening visit to determine SCA type.
Other: Blood Collection
Up to 50 milliliters of total blood (whole blood, plasma, serum) may be collected at each visit to measure markers of neurological disease.
Other: Assessments and Questionnaires
Participants will complete various motor function and cognitive assessments and self-report questionnaires.
Other: Cerebrospinal Fluid Collection
(Optional) About 1 1/2 tablespoon (25ml) of CSF collected in adults.
Participants with Spinocerebellar Ataxias (MRI Sub-study)
Adults with the spinocerebellar ataxias 1, 2, and 3 will be enrolled for genetic testing, blood collection, assessments, questionnaires, and magnetic resonance imaging (MRI).
Genetic: Genetic Testing
About two teaspoons (10 milliliters) of blood will be collected during the first/screening visit to determine SCA type.
Other: Blood Collection
Up to 50 milliliters of total blood (whole blood, plasma, serum) may be collected at each visit to measure markers of neurological disease.
Other: Assessments and Questionnaires
Participants will complete various motor function and cognitive assessments and self-report questionnaires.
Other: Magnetic Resonance Imaging (MRI) Scan
Participants in the sub-study will undergo an MRI scan of head and spine lasting up to 90 minutes at 3 Tesla strength.
Healthy Controls (MRI Sub-study)
Adults without spinocerebellar ataxias or other neurological conditions will be enrolled for genetic testing, blood collection, assessments, questionnaires, and magnetic resonance imaging (MRI).
Genetic: Genetic Testing
About two teaspoons (10 milliliters) of blood will be collected during the first/screening visit to determine SCA type.
Other: Blood Collection
Up to 50 milliliters of total blood (whole blood, plasma, serum) may be collected at each visit to measure markers of neurological disease.
Other: Assessments and Questionnaires
Participants will complete various motor function and cognitive assessments and self-report questionnaires.
Other: Magnetic Resonance Imaging (MRI) Scan
Participants in the sub-study will undergo an MRI scan of head and spine lasting up to 90 minutes at 3 Tesla strength.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Scale for the Assessment and Rating of Ataxia (SARA)
Time Frame: At baseline and then at 12 month intervals for Follow-Up Visit
The Scale for the Assessment and Rating of Ataxia (SARA) is an 8-item assessment measuring ataxia severity. Total scores are calculated as a sum of item scores and range 0-40, with higher scores indicating greater ataxia severity.
At baseline and then at 12 month intervals for Follow-Up Visit
Patient-Reported Outcome Measure of Ataxia (PROM-ataxia)
Time Frame: At baseline and then at 12 month intervals for Follow-Up Visit
The Patient-Reported Outcome Measure of Ataxia (PROM-ataxia) is a 70-item questionnaire assessing the impact of ataxia on an individual's daily life. Items are rated 0-4, where 0 indicates no difficulty/symptoms and 4 indicates severe difficulty/symptoms. Total scores are a sum of item scores and range 0 to 280 with higher scores indicating greater impact of ataxia symptoms on daily life.
At baseline and then at 12 month intervals for Follow-Up Visit
Pons Volume
Time Frame: At baseline and then at a 12 month follow-up Visit
Pons volume will be measured using MRI and divided by normalized intracranial volume. This measure is a unitless ratio.
At baseline and then at a 12 month follow-up Visit
Timed 25-Foot Walk (T25-FW)
Time Frame: At baseline and then at 12 month intervals for Follow-Up Visit
The Timed 25-Foot Walk (T25-FW) measures how fast participants can complete a 25-foot walk in seconds. The final score is an average of 2 trials. A higher scores indicates slower walking and greater gait impairment.
At baseline and then at 12 month intervals for Follow-Up Visit

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The modified Friedreich Ataxia Rating Scale - Part E (mFARS-E)
Time Frame: At baseline and then at 12 month intervals for Follow-Up Visit
The modified Friedreich Ataxia Rating Scale - Part E (mFARS-E) is a 7-item comprehensive neurological assessment of upright stability. Item E1 (Sitting) is scored 0-4, Items E2-E5 (Stance) are scored 0-4 based on how many seconds a patient can maintain position without support, and Item E6 (Tandem Walk) is scored 0-3, and Item E7 (Gait) is scored 0-5. Participants may be given up to three attempts (trials) for Items E2-E5, with each attempt recording a score 0-4, and then averaging trial scores for the total Item score. Total score is a sum of item scores on a scale of 0 to 36 points, with higher scores indicating greater impairment and loss of balance.
At baseline and then at 12 month intervals for Follow-Up Visit
Friedrich's Ataxia Activities of Daily Living (FA-ADL)
Time Frame: At baseline and then at 12 month intervals for Follow-Up Visit
The Friedrich's Ataxia Activities of Daily Living (FA-ADL) is a 9-item questionnaire measuring how ataxia affects everyday function. Items are rated 1-5 on an ordinal scale with higher scores indicating greater impairment during daily tasks. Total score is the sum of items scorings, ranging 0-36, with higher scores indicating greater impairment.
At baseline and then at 12 month intervals for Follow-Up Visit
Brief Ataxia Rating Scale (BARS)
Time Frame: At baseline and then at 12 month intervals for Follow-Up Visit
The Brief Ataxia Rating Scale (BARS) is a 5-item assessment measuring cerebellar ataxia severity. Items are scored 0-4. Total scores are a sum of item scores and range 0-20, with higher scores indicating greater ataxia severity.
At baseline and then at 12 month intervals for Follow-Up Visit
Cerebellar Cognitive Affective Syndrome (CCAS) Scale
Time Frame: At baseline and then at 12 month intervals for Follow-Up Visit
The Cerebellar Cognitive Affective Syndrome (CCAS) Scale is a screening instrument to detect the cerebellar cognitive affective syndrome in patients with cerebellar injury. The 12-item scale assesses different cognitive domains. The total possible raw score is 120 points; the Pass/Fail measure provides a maximum fail score of 10 (i.e., 10 failed tests). A fail score of 0 is normal. A participant with a fail score of 1 indicates a Possible CCAS, a fail score of 2 indicates Probable CCAS, and a fail score of 3 or more indicate Definite CCAS.
At baseline and then at 12 month intervals for Follow-Up Visit
Nine-Hole Peg Test (9-HPT)
Time Frame: At baseline and then at 12 month intervals for Follow-Up Visit
The Nine-Hole Peg Test (9-HPT) assesses upper motor dexterity by having participants place and remove 9 pegs, one at a time, as quickly as possible, with one hand at a time. Scores are reported in seconds with higher scores indicated greater upper motor impairment.
At baseline and then at 12 month intervals for Follow-Up Visit
EuroQol 5-Dimension Questionnaire (EQ-5D) Index Score
Time Frame: At baseline and then at 12 month intervals for Follow-Up Visit
The EuroQol 5-Dimension Questionnaire (EQ-5D) is a 6-item questionnaire used to assess a person's health-related quality of life. Items 1-3 are rated 1-3, items 4 and 5 are rated 1-5, and item 6 is a visual analog scale 0-100. Scores on questions 1-5 are converted into a single summary index value between 0 and 1, with lower scores indicating worse health-related quality of life.
At baseline and then at 12 month intervals for Follow-Up Visit
Fatigue Severity Scale
Time Frame: At baseline and then at 12 month intervals for Follow-Up Visit
The Fatigue Severity Scale is a 9-item scale that evaluates the impact of fatigue on a participant's life within the last week. Nine statements are rated on a scale of 1 to 7, where low values indicate strong disagreement with the statement and higher values indicate strong agreement with the statement. An additional item assess global fatigue on a scale 0 to 10, with 0 being the worst and 10 being normal. Total scores are calculated as the sum of ratings from Items 1-9, with higher scores indicating greater fatigue severity.
At baseline and then at 12 month intervals for Follow-Up Visit
Fall Questionnaire
Time Frame: At baseline and then at 12 month intervals for Follow-Up Visit
The Fall Questionnaire is a 5-item scale designed to monitor and capture a participant's number of falls, near-falls, and fall consequences based on the previous three months. Items 1-4 are rated on a scale of 0 to 3 points. Items 1-3 capture frequency of fall, near fall, and worry of falling, where a rating of 0 is Not at All in terms of frequency, up to a rating of 3 fora frequency of at least one time per week (over 13 or more times in 3 months). Item 4 is rated based on severity of injuries, if any, where 0 is Not at all for sustaining injuries, 1 is mild injuries, 2 is moderate injuries, and 3 is severe injuries. The scores from all four questions are summed to give a total score of 0-12 points, where higher scores indicate more severe fall history. Item 5 captures qualitative information on the circumstances of the fall and possible causes.
At baseline and then at 12 month intervals for Follow-Up Visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lauren Moore

Collaborators

Johns Hopkins University
Massachusetts General Hospital
University of Pennsylvania
University of South Florida
University of California, Los Angeles
Northwestern University
University of Chicago
Columbia University
University of Michigan
Emory University
University of Florida
University of Washington
Centre hospitalier de l'Université de Montréal (CHUM)
University of California, San Francisco
University of Minnesota
University of Texas Southwestern Medical Center
National Ataxia Foundation
The Methodist Hospital Research Institute

Investigators

  • Principal Investigator: Vikram Shakkottai, MD, PhD, University of Texas
  • Principal Investigator: Liana Rosenthal, MD, PhD, Johns Hopkins University
  • Principal Investigator: Sheng-Han Kuo, MD, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2010

Primary Completion (Estimated)

December 1, 2030

Study Completion (Estimated)

December 1, 2030

Study Registration Dates

First Submitted

January 29, 2010

First Submitted That Met QC Criteria

January 29, 2010

First Posted (Estimated)

February 2, 2010

Study Record Updates

Last Update Posted (Actual)

August 3, 2026

Last Update Submitted That Met QC Criteria

July 30, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB201700740
  • 505-2009 (Other Identifier: Legacy study)
  • OCR16458 (Other Identifier: Universiy of Florida)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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