Prospective Study of Individuals at Risk for Spinocerebellar Ataxia Type 1, Type 2, Type 3, Type 6 and Type 7 (SCA1, SCA2, SCA3, SCA6, SCA7)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 37
- 试验地点
- 2
- 主要终点
- Determination of the incidence rate of ataxia onset among mutation carriers
研究概览
简要总结
The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of autosomal dominantly inherited progressive ataxia disorders. It is estimated that there are 30,000 individuals in the European Community that directly descend from individuals affected by a SCA disorder and thus carry a 50% risk of having inherited an SCA mutation. These at risk individuals provide a unique research opportunity to prospectively study the presymptomatic phase of SCA disorders and to identify the earliest and most sensitive clinical signs and biological markers that herald the onset of the illness. This information is of critical importance for the development of future therapeutic interventions aimed at postponing the clinical onset of ataxia.
We therefore propose to perform a prospective observational study of individuals at risk for the most common SCA disorders, SCA1, SCA2, SCA3 and SCA6 (RISCA). It is our aim to answer the following questions: (1) What is the incidence of disease manifestation in mutation carriers? (2) Which clinical signs precede the onset of manifest ataxia in SCA1, SCA2, SCA3 and SCA6? (3) What are the prevalence and incidence of preceding signs? (4) Are the prevalence and incidence of preceding signs affected by genotype, gender, age, estimated time until disease manifestation and repeat length? (5) Does the presence of certain preceding signs predict the manifestation of ataxia ? (6) Are there MRI alterations that precede the onset of ataxia? It is planned to enroll 480 study participants and to follow them at regular intervals over six years. At each visit, study participants are asked in a structured interview for a number of predefined clinical signs that potentially precede the onset of ataxia. In addition, the following self-assessment scales will be applied: Pittsburgh Sleep Quality Index (PSQI), Diagnostic Criteria for Restless Legs Syndrome, Patient´s Health Questionnaire (PHQ-9). All study participants will undergo a physical examination including the Scale for the Assessment and Rating of Ataxia (SARA). Study participants will further perform the SCA Functional Composite (SCA-FC) which is a comprehensive measure of functional capacity based on results in quantitative tests related to gait (8m timed walk), speech (PATA rate) and hand function (9 hole pegboard). In a subset of study participants, we will record eye movements and obtain volumetric MRIs. The study will also be used to collect and store blood and urine samples for proteomic and gene expression studies.
RISCA is conducted by the Ataxia Study Group (ASG). It relies on the network structure created by the EUROSCA project.
研究设计
- 研究类型
- Observational
- 观察模型
- Family Based
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •individuals at risk for spinocerebellar ataxia type 1, type 2, type 3, type 6 and type 7 (SCA1, SCA2, SCA3, SCA6 and SCA7)
- •age between 18 and 50 years old for SCA1, SCA2, SCA3 or SCA7
- •age between 35 and 70 years old for SCA6
- •no clinical sign of ataxia (SARA < 3)
排除标准
- •no writing consent
- •no family members affected
- •presence of clinical sign of ataxia (SARA > 3)
结局指标
主要结局
Determination of the incidence rate of ataxia onset among mutation carriers
时间窗: Day 0
Blood sample for a genetic test. Identification of individuals carrying a mutation for SCA types 1, 2, 3, 6, and 7
Confidence Rating for Ataxia Assessment
时间窗: Day 0, Month 24, Month 48, Month 72
The invetigator must specify the degree of confidence in the presence of specific signs that may be associated with SCA ataxia . 90-100 % : investigator very confident in the diagnosis of ataxia, 70-89 % : high confidence, but with some uncertainty, 50-69 % : moderate confidence, \<50 % : significant uncertainty.
INAS scoring in ataxia (Inventory of Non-Ataxia Signs)
时间窗: Day 0, Month 24, Month 48, Month 72
Score range 0-16. 0 : No nonataxia signsdetected. Higher score : more non-ataxia neurological signs are present
Assessmet of sleep quality in ataxia : PSQI (Pittsburg Sleep Quality Index)
时间窗: Day 0, Month 24, Month 48, Month 72
The global PSQI score ranges from 0 to 21. 0-5 : good sleep quality. \>5 : Poor sleep quality / clinically significant slep disturbance. Higher scores : worse sleep quality
Restless Legs Syndrome (RLS) assessment in Ataxia
时间窗: Day 0, Month 24, Month 48, Month 72
Total Score : 0-40 0 : No RLS symptoms, 1-10 : Mild, 11-20 : Moderate, 21-30 : Severe, 31-40 : Very severe.
Assessment of depression by Patient's Health Questionnaire PHQ-9
时间窗: Day 0, Month 24, Month 48, Month 72
Used to evaluatethe severity of depressive symptoms, giving a total score rangong from 0 to 27. 0-4 : minimal or no deprssive symptoms, 5-9 : mild depression, 10-14 : moderate depression, 15-19 : moderately severe depression, 20-27 : severe depression
Assessment of the disease's impact on quality of life based on EQ-5D index (EuroQoL-5 Dimensions)
时间窗: Day 0, Month 24, Month 48, Month 72
It generally ranges from less than 0 to 1 (perfect health). Higher scores indicate a better quality of life
Assessment and Rating of Ataxia
时间窗: Day 0, Month 24, Month 48, Month 72
SARA (Scale of Assessment and Rating Ataxia) is an 8-item performance based scale, yielding a total score of 0 (no ataxia) to 40 (most severe ataxia).
Functional assessment of the severity of ataxia
时间窗: Day 0, Month 24, Month 48, Month 72
Using CCFS (Composite Cerebellar Functional Severity Score) method for assessing cerebellar ataxia across a wide range of severity. =0,85 : average value in an individual without ataxia. 0,90-1,00 : very mild or early-stage cerebellar impairment. 1,00-1,20 : Mild to moderate cerebellar impairment. \>1,2 : More pronounced cerebellar impairment.
Upper Limb motor coordination assessment
时间窗: Day 0, Month 24, Month 48, Month 72
A device equipped with a pre-calibrated force sensor that measures grip strength and lifting capacity, and a Polhemus 3D position sensor that measures position along the -x, -y, and -z axes and the object's orientation to assess movement. Grip force variability coefficient is calculated : Lowe % (more stable greap force control) - Higher % (greater variability and poorer motor coordination)
Finger tapping assessment
时间窗: Day 0, Month 24, Month 48, Month 72
Number of taps within 10 seconds (higher = better)
GAITRite in an ataxia assessment
时间窗: Day 0, Month 24, Month 48, Month 72
The participant walks along a carpet equipped with sensors that record the time it takes to make a step as well as the position of the feet.
次要结局
- Functional performance assessment by 8MW test (8 meters walking time)(Day 0, Month 24, Month 48, Month 72)
- Functional performance assessment by 9HPT : Nine Hole Peg Test(Day 0, Month 24, Month 48, Month 72)
- Functional performance assessment by by PATA(Day 0, Month 24, Month 48, Month 72)
- Assessment of retinal thickness(Day 0, Month 24, Month 48, Month 72)
- Identification of slow saccades during eye tracking(Day 0, Month 24, Month 48, Month 72)
- Evaluation of the functional connectivity(Day 0, Month 72)