SNPMiner Trials (Home Page)
Report for SNP rs41524745
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There is one clinical trial.
Clinical Trials
1 Genetic Mechanism of Conserved Ancestral Haplotype in SCA10
Spinocerebellar ataxia type 10 (SCA10) is a hereditary ataxia whose ancestral mutation occurred in East Asia. The mutation is likely to have migrated during peopling of American continents from East Asia. We found a specific rare DNA variation associated with SCA10. We test whether this variation played a key role in the birth and subsequent spreading of SCA10 mutation.
NCT04495426 Spinocerebellar Ataxia Type 10 Other: Non-interventional study MeSH:Ataxia Spinocerebellar Ataxias Spinocerebellar Degenerations
HPO:Dyssynergia Incoordination Limb ataxia Rubral tremor Sensory ataxia Spinocerebellar atrophy Truncal ataxia
SCA10 families from LA and EA share an ancestral haplotype that includes the G allele (allele frequency: 2-4% in EA and LA populations but 0% elsewhere) of a C/G/T single nucleotide polymorphism (SNP) at rs41524745 (https://www.ncbi.nlm.nih.gov/snp/rs41524547#frequency_tab).
Two characteristics suggest that rs41524745 has a functional role over the expansion: this SNP resides in the sequence encoding miR4762; and total linkage between the SNP and the SCA10 repeat, although they are ~35kb apart, a distance sufficient for multiple recombination events within the 15,000-20,000 years since human migration across Bering landmass.
Primary Outcomes
Description: Scale for the assessment and rating of ataxia (SARA) was evaluated in two large validation trials performed by the EUROSCA clinical group and was found to be easy to use, reliable and valid. SARA has eight categories with accumulative score ranging from 0 (no ataxia) to 40 (most severe ataxia).
Measure: Examine the disease progression in SCA10 as determined by change in the scale for the assessment and rating of ataxia score compared to healthy controls Time: Baseline visit 1, Follow up visit (12-18 months after visit 1)Description: The Spinocerebellar Ataxia Functional Index (SCAFI) is composed of: Timed 8 meter walk at maximum speed (8MW). Times are only given for two successfully completed trials. Discontinue the test if participant cannot complete trial in 3 minutes (more severe ataxia). Timed dexterity test: 9-hole peg test (9HPT). Times are only given for two successfully completed trials for each hand. If participant cannot complete one trial in 5 minutes (more severe ataxia) discontinue 9-hole-peg test. Timed speech test: PATA rate, a measure of speech performance. The participant is asked to repeat "PATA" as quickly and distinctly as possible for 10 seconds until told to stop. As soon as the participant begins speaking, start timer and begin counting the number of PATA repeats. Higher number (less dysarthria), lower number (more dysarthria). Discontinue if PATA articulation is too difficult to distinguish for counting or if participant cannot complete 10 seconds for two consecutive trials.
Measure: Examine the disease progression in SCA10 as determined by change in Spinocerebellar Ataxia Functional Index score compared to healthy controls Time: Baseline visit 1, Follow up visit (12-18 months after visit 1)Description: The Composite Cerebellar Functional Severity (CCFS) score is a quantitative tool to measure cerebellar severity independently from age. It is an assessment in addition to a clinical examination and has demonstrated its usefulness in epidemiological studies, clinical trials, and patient follow-up that only take 5 minutes to be administrated. The CCFS is a combination of the time to perform 2 tasks; a 9-hole pegboard and a click test. It was validated in adults and children. CCFS scores range from 0.50 (normal/no ataxia) to 1.80 (more severe ataxia).
Measure: Examine the disease progression in SCA10 as determined by change in Composite Cerebellar Functional Severity Score compared to healthy controls Time: Baseline visit 1, Follow up visit (12-18 months after visit 1)Description: The Neurological Examination Score for Spinocerebellar Ataxia (NESSCA) scale is based on the standardized neurological examination, and consists of 18 items that yield a total score ranging from 0 (no ataxia) to 40 (most severe ataxia). The NESSCA is a comprehensive measure of disease severity that was shown to be both clinically useful and scientifically valid.
Measure: Examine the disease progression in SCA10 as determined by change in Neurological Examination Score for Spinocerebellar Ataxia compared to healthy controls Time: Baseline visit 1, Follow up visit (12-18 months after visit 1)Description: The Inventory of Non-ataxia Symptoms (INAS) is a scale utilized in recording the occurrence of accompanying non-ataxia symptoms. In the SARA validation trials, INAS was applied to a large number of SCA patients. For a semiquantitative assessment of non-ataxia signs, the number of non-ataxia signs is counted yielding the INAS count, a dimensionless value with a range from 0 (no ataxia) to 16 (most severe ataxia). To determine the INAS count, only the presence or absence of one of the 16 signs is considered. Statistical evaluation showed good reliability.
Measure: Examine the disease progression in SCA10 as determined by change in Inventory of Non-ataxia Symptoms score compared to healthy controls Time: Baseline visit 1, Follow up visit (12-18 months after visit 1)Description: The Beck Depression Inventory (BDI) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression. Answers can range from 0 to 3 for each item. The total score will range from 0 (considered normal) to 40 (extreme depression).
Measure: Examine the disease progression in SCA10 as determined by change in Beck Depression Inventory score compared to healthy controls Time: Baseline visit 1, Follow up visit (12-18 months after visit 1)Description: The Europe Quality of Life-5 Dimension (Euro Qol-5D or EQ-5D), is a measure developed by the EuroQol Group that generates a single index value for health status with considerable potential for use in health care evaluation.The EQ-5D descriptive system is a preference-based HRQL measure with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The answers given to ED-5D permit to find 243 unique health states or can be converted into EQ-5D index an utility scores anchored at 0 for death and 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status).
Measure: Examine the disease progression in SCA10 as determined by change in Europe Quality of Life-5 Dimension score compared to healthy controls Time: Baseline visit 1, Follow up visit (12-18 months after visit 1)Description: Electroencephalography (EEG) will be obtained and analyzed for changes that may be distinctive for SCA10: seizure spikes and/or sharp waves during and, sometimes, between seizure episodes.
Measure: Number of participants with Electroencephalography changes that may be distinctive for SCA10 Time: Baseline visit 2 (within 6 weeks of visit 1)Description: Magnetic Resonance Imaging (MRI) using a 3T scanner will be used to measure cerebellar and brainstem volumes.
Measure: Examine the level of disease activity based on change in cerebellar and brainstem volumes compared to healthy controls Time: Baseline visit 2 (within 6 weeks of visit 1)Description: Magnetic Resonance Imaging (MRI) will be used to measure change in grey matter volume and white matter volume from voxel-based morphometric data.
Measure: Examine the level of disease activity based on change in grey matter and white matter loss metrics from voxel-based morphometry compared to healthy controls Time: Baseline visit 2 (within 6 weeks of visit 1)Description: Magnetic Resonance Imaging (MRI) will be used to measure change in mean diffusivity.
Measure: Examine the level of disease activity based on change in mean diffusivity compared to healthy controls Time: Baseline visit 2 (within 6 weeks of visit 1)Description: Magnetic Resonance Imaging (MRI) will be used to measure change in radial and axial diffusivity.
Measure: Examine the level of disease activity based on change in radial and axial diffusivity compared to healthy controls Time: Baseline visit 2 (within 6 weeks of visit 1)