Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias

Condition(s) studied

Investigational drug(s) / intervention(s)

Genetic Testing: About two teaspoons (10 milliliters) of blood will be collected during the first/screening visit to determine SCA type.

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.

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.

Assessments and Questionnaires: Participants will complete various motor function and cognitive assessments and self-report questionnaires.

Cerebrospinal Fluid Collection: (Optional) About 1 1/2 tablespoon (25ml) of CSF collected in adults.

Study 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.

Eligibility

Primary outcome measure(s)

• Scale for the Assessment and Rating of Ataxia (SARA) — 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.
• Patient-Reported Outcome Measure of Ataxia (PROM-ataxia) — 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.
• Pons Volume — 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.
• Timed 25-Foot Walk (T25-FW) — 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.

Trial sites (17)

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