Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias

Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) to Study 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 SCA and this study will focus on types 1, 2,3, and 6 (SCA 1, SCA 2, SCA 3 , also known as Machado-Joseph disease and SCA 6). 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 does your disease 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 your disease, have any effect on the way the disease behaves?

This is a nationwide study and we expect that 800 patients will participate all over the USA. The participants will be in the study for an indeterminate period of time. Study visits will be done every 6 or 12 months depending on the participating site.

Study Overview

• Status: Recruiting
• Conditions: Spinocerebellar Ataxia Type 3; Spinocerebellar Ataxia Type 1; Spinocerebellar Ataxia Type 2; Spinocerebellar Ataxia Type 6
• Intervention / Treatment: Genetic: All Participants

Detailed Description

If you decide to participate in this study, we will collect 1 tablespoon (15 milliliters) of blood during the first/screening visit in order to extract your DNA. The sample will be sent to the research laboratory of Dr Stefan Pulst at the University of Utah for the study of genetic factors that modify the course of your disease.

As part of this study, we would like to put some of your blood in a tissue repository. Submission of your sample to the repository may give scientists valuable research material that can help them to develop new diagnostic tests, new treatments, and new ways to prevent diseases. Scientists will not use your sample, or material isolated from it, for commercial products or services. Your blood will be kept by Dr. Stefan Pulst.

Your sample will not have your name or other personal information linked to it. Your sample may be shared with researchers at the University of Utah and at other institutions. The only information we will keep with the sample is your age, what disease you have, the age at onset of your disease and the duration of the disease. The principal investigator at your site will be the only person who can link the sample to you. You can have your sample removed from the bank later by written request to your PI.

You do not have to participate in the genetic modifier study or the tissue repository to be in the remaining part of this study.

You will also be asked to complete several assessments that include questionnaires, motor function test, a neurological exam and a physical exam.

• Study Type: Observational
• Enrollment (Estimated): 800

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California Los Angeles
      • Contact: Brian Clemente; Phone Number: 310-206-8153; Email: bclemente@mednet.ucla.edu
      • Principal Investigator: Susan Perlman, M.D.
    • San Francisco, California, United States, 94115
      • Recruiting
      • University of California San Francisco
      • Contact: Julia Glueck; Phone Number: 415-502-7640; Email: julia.glueck@ucsf.edu
      • Principal Investigator: Michael Geschwind, MD
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida
      • Contact: SH Subramony, MD; Phone Number: 352-273-5550; Email: s.subramony@neurology.ufl.edu
      • Principal Investigator: S H Subramony, MD
    • Tampa, Florida, United States, 33620
      • Active, not recruiting
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30320
      • Recruiting
      • Emory University
      • Contact: Rebecca MacMurray; Phone Number: 404-728-4909; Email: rebecca.s.mcmurray@emory.edu
      • Principal Investigator: George Wilmot, M.D., PhD.
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Active, not recruiting
      • University of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • John Hopkins University
      • Contact: Ann Fishman; Phone Number: 410-502-5816; Email: ataxiaresearch@jhu.edu
      • Principal Investigator: Chiadi Onyike, M.D., MHS
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Harvard University
      • Contact: Jason MacMore; Phone Number: 617-726-3216; Email: jmacmore@partners.org
      • Principal Investigator: Jeremy Schmahmann, M.D.
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Active, not recruiting
      • University of Michigan
  • 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: Sheng-Han Kuo, MD; Phone Number: 212-305-5558; Email: sk3295@mail.cumc.colombia.edu
      • Principal Investigator: Pietro Mazzoni, M.D., PhD.
      • Sub-Investigator: Sheng-Han Kuo, M.D.
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Active, not recruiting
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) is seeking subjects to participate in a clinical research study of patients with SCA 1, 2 3 and 6.

Potential participants should have symptoms of ataxia with a diagnosis of SCA 1,2,3 or 6 established by DNA tests either on the patient himself or herself or another affected family member and be between 6 and 80 years of age. In addition, patients who have ataxia with a dominant inheritance pattern but who do not yet know what type of SCA they have can also be screened for this project.

Description

Inclusion Criteria:

• Presence of symptomatic ataxic disease
• Definite molecular diagnosis of SCA 1, 2,3,or 6 either in the subject or another affected family member
• Willingness to participate in the study and ability to give informed consent.
• Age 6 years and above

Exclusion Criteria:

• Known recessive, X-linked and mitochondrial ataxias
• Exclusion of SCA 1, 2, 3 and 6 by previous DNA testing,
• A lack of willingness to participate in the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Spinocerebellar Ataxia 1; If you decide to participate in this study, the following study procedures will be performed: blood collection for DNA testing, analysis (genetic modifier study) and banking; Medical history; Physical exam; Scale for Assessment and Rating of Ataxia (SARA); Timed measure of your hand dexterity and walking (25 ft); Questionnaire about your daily living activities, your physical and mental quality of life and assessment of depression.; Disease stage estimation by the clinician.; Demographics and disease-related information (i.e. age, sex, race, age at disease onset, disease duration); Review of your medical records	Genetic: All Participants; If you decide to participate in this study, we will collect 1 tablespoon (15 milliliters) of blood during the first/screening visit in order to extract your DNA.
Spinocerebellar Ataxia 2; If you decide to participate in this study, the following study procedures will be performed: blood collection for DNA testing, analysis (genetic modifier study) and banking; Medical history; Physical exam; Scale for Assessment and Rating of Ataxia (SARA); Timed measure of your hand dexterity and walking (25 ft); Questionnaire about your daily living activities, your physical and mental quality of life and assessment of depression.; Disease stage estimation by the clinician.; Demographics and disease-related information (i.e. age, sex, race, age at disease onset, disease duration); Review of your medical records	Genetic: All Participants; If you decide to participate in this study, we will collect 1 tablespoon (15 milliliters) of blood during the first/screening visit in order to extract your DNA.
Spinocerebellar Ataxia 3; If you decide to participate in this study, the following study procedures will be performed: blood collection for DNA testing, analysis (genetic modifier study) and banking; Medical history; Physical exam; Scale for Assessment and Rating of Ataxia (SARA); Timed measure of your hand dexterity and walking (25 ft); Questionnaire about your daily living activities, your physical and mental quality of life and assessment of depression.; Disease stage estimation by the clinician.; Demographics and disease-related information (i.e. age, sex, race, age at disease onset, disease duration); Review of your medical records	Genetic: All Participants; If you decide to participate in this study, we will collect 1 tablespoon (15 milliliters) of blood during the first/screening visit in order to extract your DNA.
Spinocerebellar Ataxia 6; If you decide to participate in this study, the following study procedures will be performed: blood collection for DNA testing, analysis (genetic modifier study) and banking; Medical history; Physical exam; Scale for Assessment and Rating of Ataxia (SARA); Timed measure of your hand dexterity and walking (25 ft); Questionnaire about your daily living activities, your physical and mental quality of life and assessment of depression.; Disease stage estimation by the clinician.; Demographics and disease-related information (i.e. age, sex, race, age at disease onset, disease duration); Review of your medical records	Genetic: All Participants; If you decide to participate in this study, we will collect 1 tablespoon (15 milliliters) of blood during the first/screening visit in order to extract your DNA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The disease's progression over time using clinical rating scales and timed performance measures.	Indefinitely (for as long as the study is open and you wish to participate)
Relation between the genetic modifiers and the age at onset of disease and disease progression rates.	Indefinitely (for as long as the study is open and you wish to participate)

Secondary Outcome Measures

Outcome Measure	Time Frame
The effects of the disease on the Activities of Daily Living (ADL)in patients with Spinocerebellar Ataxias	indefinitely

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: University of California, Los Angeles; National Ataxia Foundation
• Investigators: Principal Investigator: S. Subramony, MD, University of Florida

Publications and helpful links

Helpful Links

• National Ataxia Foundation

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2010
• Primary Completion (Estimated): May 19, 2024
• Study Completion (Estimated): May 19, 2024

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): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Natural History; Spinocerebellar Ataxia; Genetic Modifiers; DNA testing
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Cerebellar Diseases; Ataxia; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations; Machado-Joseph Disease
• Other Study ID Numbers: IRB201700740; 505-2009 (Other Identifier: Legacy study); OCR16458 (Other Identifier: Universiy of Florida)

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