Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias

Summary

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.

Conditions

• Spinocerebellar Ataxia Type 1
• Spinocerebellar Ataxia Type 2
• Spinocerebellar Ataxia Type 3
• Spinocerebellar Ataxia Type 6
• Spinocerebellar Ataxia Type 7
• Spinocerebellar Ataxia Type 8
• Spinocerebellar Ataxia Type 10
• RFC1 Gene Mutation
• Spinocerebellar Ataxia Type 27b
• Healthy Participants

Interventions

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

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.

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.

Sponsors & Collaborators

• University of California, Los Angeles

  collaborator OTHER

• University of South Florida

  collaborator OTHER

• National Ataxia Foundation

  collaborator OTHER

• Columbia University

  collaborator OTHER

• Johns Hopkins University

  collaborator OTHER

• University of Texas Southwestern Medical Center

  collaborator OTHER

• The Methodist Hospital Research Institute

  collaborator OTHER

• University of California, San Francisco

  collaborator OTHER

• University of Florida

  collaborator OTHER

• Emory University

  collaborator OTHER

• University of Chicago

  collaborator OTHER

• Northwestern University

  collaborator OTHER

• University of Michigan

  collaborator OTHER

• University of Minnesota

  collaborator OTHER

• Massachusetts General Hospital

  collaborator OTHER

• Centre hospitalier de l'Université de Montréal (CHUM)

  collaborator OTHER

• University of Pennsylvania

  collaborator OTHER

• University of Washington

  collaborator OTHER

• Lauren Moore

  lead OTHER

Principal Investigators

• Liana Rosenthal, MD, PhD · Johns Hopkins University

• Sheng-Han Kuo, MD · Columbia University

• Vikram Shakkottai, MD, PhD · University of Texas

Eligibility

Min Age

6 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2010-04-30

Primary Completion

2030-12-31

Completion

2030-12-31

Countries

• United States
• Canada

Study Locations