The EUROSCA Natural History Study

Study Overview
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Brief Summary
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The key goals of EUROSCA-NHS is to determine and compare the rate of disease progression in SCA1, SCA2, SCA3 and SCA6 including determination of the order and occurrence of non-ataxia symptoms, assessment of activities of daily living (ADL) and quality of life (QoL), and identification of predictors of disease progression and survival.

Detailed Description
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The key goal of EUROSCA-NHS is to determine and compare the rate of disease progression in SCA1, SCA2, SCA3 and SCA6. To this end, a newly developed and validated ataxia scale (Scale for the Assessment and Rating of Ataxia, SARA) will be used. EUROSCA-NHS has a number of secondary aims including determination of the order and occurrence of non-ataxia symptoms, assessment of activities of daily living (ADL) and quality of life (QoL), and identification of predictors of disease progression and survival. Substudies will deal with the development of brain atrophy, as assessed by magnetic resonance imaging (MRI), progression of peripheral neuropathy, as assessed by nerve conduction studies, and specific clinical aspects of SCA.

Official Title
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The EUROSCA Natural History Study

Conditions
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Spinocerebellar Ataxia

Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Progressive, otherwise unexplained ataxia Positive genetic testing for SCA1, SCA2, SCA3, and SCA6 Written informed consent by the patient or his legal agent Exclusion criteria: None.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Spinocerebellar ataxia type 1,2,3 and 6<br>Spinocerebellar ataxias (SCA) are autosomal dominantly inherited progressive ataxia disorders. An epidemiological study performed in the Netherlands found a prevalence of 3.0 : 100,000 (van de Warrenburg et al. 2002). The SCA´s are genetically and clinically heterogeneous disorders with SCA1, SCA2, SCA3 and SCA6 being the most frequent genotypes worldwide. While SCA1, SCA2 and SCA3 have a complex phenotype, SCA6 patients usually present with pure cerebellar ataxia (Schols et al. 2004). Although precise knowledge of the rate of disease progression is a prerequisite for the biometrical design of future therapeutical trials, prospective studies of the natural history of SCA´s have not been performed. Similarly, the occurrence and evolution of accompanying non-ataxia symptoms have not been studied prospectively. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scale for the assessment and rating of ataxia (SARA) | Progression of ataxia is measured using a newly developed and validated ataxia scale, SARA. 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. | Patients are first seen at a baseline visit, followed by annual visits for 3 years scheduled ± 3 months around the specified time point. After the initial 3 year observation period, visits are done at irregular intervals each time they went to hospital. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease stages | Disease stages are measured using the 5 point scale ranging from 0 to 4 proposed by Klockgether et al., 1998. | Patients are first seen at a baseline visit, followed by annual visits for 3 years scheduled ± 3 months around the specified time point. After the initial 3 year observation period, visits are done at irregular intervals each time they went to hospital. | 
| Inventory of non-ataxia signs (INAS) | The occurrence of accompanying non-ataxia symptoms is recorded using INAS. In the SARA validation trials, INAS was applied to a large number of SCA patients. Statistical evaluation showed good reliability. | Patients are first seen at a baseline visit, followed by annual visits for 3 years scheduled ± 3 months around the specified time point. After the initial 3 year observation period, visits are done at irregular intervals each time they went to hospital. | 
| UHDRS part IV | Functional disability in ADL is assessed using the Functional assessment part of the Unified Huntington's Disease Rating Scale (UHDRS) (Huntington Study Group, 1996). This 25-item assessment has been used in SCA patients throughout the SARA validation study with good practicality. | Patients are first seen at a baseline visit, followed by annual visits for 3 years scheduled ± 3 months around the specified time point. After the initial 3 year observation period, visits are done at irregular intervals each time they went to hospital. | 
| EQ-5D | Health related Quality of life is assessed using EQ-5D, a generic instrument that has been developed and validated by the EuroQuol Group (1990) and is available in validated translations for use as a questionnaire. | Patients are first seen at a baseline visit, followed by annual visits for 3 years scheduled ± 3 months around the specified time point. After the initial 3 year observation period, visits are done at irregular intervals each time they went to hospital. | 
| PHQ-9 | Assessment of depressive symptoms is done using a validated 9-item short form of the Patient Health Questionnaire (PHQ), a questionnaire that has been developed to screen for psychiatric co-morbidity in unselected populations (Spitzer et al. 1999). | Patients are first seen at a baseline visit, followed by annual visits for 3 years scheduled ± 3 months around the specified time point. After the initial 3 year observation period, visits are done at irregular intervals each time they went to hospital. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Natural History