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.
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
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.
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.
Cohort
Prospective
Genetic Testing
GeneticAbout two teaspoons (10 milliliters) of blood will be collected during the first/screening visit to determine SCA type.
Blood Collection
Other interventionUp 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
Other interventionParticipants 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
Other interventionParticipants will complete various motor function and cognitive assessments and self-report questionnaires.
Cerebrospinal Fluid Collection
Other intervention(Optional) About 1 1/2 tablespoon (25ml) of CSF collected in adults.
Scale for the Assessment and Rating of Ataxia (SARA)
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)
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
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)
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.
The modified Friedreich Ataxia Rating Scale - Part E (mFARS-E)
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.
Friedrich's Ataxia Activities of Daily Living (FA-ADL)
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.
Brief Ataxia Rating Scale (BARS)
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.
Cerebellar Cognitive Affective Syndrome (CCAS) Scale
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.
Click on the lead sponsor to view all of their trials.
Lauren Moore
Lead sponsor
National Ataxia Foundation
Sponsor institution
University of California, Los Angeles
Collaborator
University of South Florida
Collaborator
National Ataxia Foundation
Collaborator
Columbia University
Collaborator
Johns Hopkins University
Collaborator
University of Texas Southwestern Medical Center
Collaborator
The Methodist Hospital Research Institute
Collaborator
University of California, San Francisco
Collaborator
University of Florida
Collaborator
Emory University
Collaborator
University of Chicago
Collaborator
Northwestern University
Collaborator
University of Michigan
Collaborator
University of Minnesota
Collaborator
Massachusetts General Hospital
Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)
Collaborator
University of Pennsylvania
Collaborator
University of Washington
Collaborator
