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
Conditions
Keywords
Spinocerebellar Ataxia, Natural History, Genetic Modifiers, Biomarkers
Brief 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.
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.
Interventions
GENETICGenetic Testing
About two teaspoons (10 milliliters) of blood will be collected during the first/screening visit to determine SCA type.
OTHERBlood Collection
Up to 50 milliliters of total blood (whole blood, plasma, serum) may be collected at each visit to measure markers of neurological disease.
Participants in the sub-study will undergo an MRI scan of head and spine lasting up to 90 minutes at 3 Tesla strength.
Participants will complete various motor function and cognitive assessments and self-report questionnaires.
(Optional) About 1 1/2 tablespoon (25ml) of CSF collected in adults.
Sponsors
Lauren Moore
University of California, Los Angeles
University of South Florida
National Ataxia Foundation
Columbia University
Johns Hopkins University
University of Texas Southwestern Medical Center
The Methodist Hospital Research Institute
University of California, San Francisco
University of Florida
Emory University
University of Chicago
Northwestern University
University of Michigan
University of Minnesota
Massachusetts General Hospital
Centre hospitalier de l'Université de Montréal (CHUM)
University of Pennsylvania
University of Washington
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The modified Friedreich Ataxia Rating Scale - Part E (mFARS-E) | 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. |
| Friedrich's Ataxia Activities of Daily Living (FA-ADL) | 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. |
| Brief Ataxia Rating Scale (BARS) | 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. |
| Cerebellar Cognitive Affective Syndrome (CCAS) Scale | 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. |
| Nine-Hole Peg Test (9-HPT) | 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. |
| EuroQol 5-Dimension Questionnaire (EQ-5D) Index Score | 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. |
| Fatigue Severity Scale | 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. |
| Fall Questionnaire | 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. |
Countries
Canada, United States
Contacts
CONTACTLaura P Crespo
PRINCIPAL_INVESTIGATORLiana Rosenthal, MD, PhD
Johns Hopkins University
PRINCIPAL_INVESTIGATORSheng-Han Kuo, MD
Columbia University
PRINCIPAL_INVESTIGATORVikram Shakkottai, MD, PhD
University of Texas
Outcome results
None listed