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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-A02563-52 | Registry Identifier | Secondary ID |
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| Name | Class |
|---|---|
| Biogen | INDUSTRY |
| Ionis Pharmaceuticals, Inc. | INDUSTRY |
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One of the main objectives of this project is to validate potential biological, clinical and/or imaging biomarkers in SCA patients through a multimodal assessment, for future ASOs trials.
Spinocerebellar ataxias (SCAs) are autosomal dominantly inherited neurological disorders, characterized by a predominant atrophy of the cerebellum and the brainstem. The most common forms are caused by abnormal CAG repeat expansions, encoding elongated polyglutamine (polyQ).
Nowadays, no preventive or curative treatments are available but different therapeutic approaches are ongoing. Antisense oligonucleotides (ASOs) therapy showed promising results in Huntington disease (HD), a disease that shares with the SCAs the same mutational mechanism. ASOs are currently under development for SCAs.
However, in SCAs, clinical scales as an only criteria to monitor a treatment are not appropriate because of the lack of sensitivity of change and the small number of patients available. The importance to dispose of outcome measures to inform about the efficacy of a treatment is fundamental as well as of new alternative designs to conduct a clinical trial in rare diseases with small sample sizes.
A comprehensive, multimodal approach is hence needed to provide a translational and integrated overview of cerebellar dysfunction in polyQ SCAs over a year.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SCA early-manifest and premanifest patients | This cohort is defined by individuals with a SARA score between 0 and 15 (both values included). |
| |
| Control participants | This cohort is defined by individuals with a SARA score less than 5 and no significant neurological symptoms. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lumbar puncture | Procedure | Each participant will undergo lumbar puncture at first visit (M0) and last visit (M12) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Identification of biological, clinical and/or imaging biomarkers in SCA2 and SCA7 patients mutations carriers and patients through a multimodal assessment over one year to prepare therapeutic trials | Over one year |
| Measure | Description | Time Frame |
|---|---|---|
| To determine the cross-sectional and longitudinal variability of SARA (Scale for the Assessment and Rating of Ataxia) and CCFS (Composite Cerebellar Functional Score) scores in SCA 2 and SCA 7 gene mutation carriers and healthy controls over one | Over one year | |
| Determine the cross-sectional and longitudinal variability of volumetric MRI and NMR-proto spectroscopy in SCA 2 and SCA 7 gene mutation carriers and healthy controls |
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Common inclusion criteria for all participants:
Inclusion criteria for SCA patients:
Inclusion criteria for control participants:
Common inclusion criteria for elective participant for CSF sampling:
• Ability to undergo a lumbar puncture
Exclusion criteria
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| Name | Affiliation | Role |
|---|---|---|
| Alexandra DURR | Institut du Cerveau - Paris Brain Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institut du Cerveau - Paris Brain Institute | Paris | 75013 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39133883 | Result | Coarelli G, Dubec-Fleury C, Petit E, Sayah S, Fischer C, Nassisi M, Gatignol P, Dorgham K, Daghsen L, Daye P, Cunha P, Kacher R, Hilab R, Hurmic H, Lamaziere A, Lamy JC, Welter ML, Chupin M, Mangin JF, Lane R, Gaymard B, Pouget P, Audo I, Brice A, Tezenas du Montcel S, Durr A. Longitudinal Changes of Clinical, Imaging, and Fluid Biomarkers in Preataxic and Early Ataxic Spinocerebellar Ataxia Type 2 and 7 Carriers. Neurology. 2024 Sep 10;103(5):e209749. doi: 10.1212/WNL.0000000000209749. Epub 2024 Aug 12. | |
| 38421662 |
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| ID | Term |
|---|---|
| D020754 | Spinocerebellar Ataxias |
| ID | Term |
|---|---|
| D002524 | Cerebellar Ataxia |
| D002526 | Cerebellar Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D013129 | Spinal Puncture |
| D009682 | Magnetic Resonance Spectroscopy |
| ID | Term |
|---|---|
| D001706 | Biopsy |
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
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Whole blood collected for DNA analysis
| Magnetic Resonance Imaging (MRI) | Other | Each participant will undergo scanning at 3 visits (M0, M6 and M12) |
|
| Over one year |
| Delineate a specific pattern of frontal-like cognitive deficit in SCAs gene carriers | Evolution of neuropsychological scores and Cerebellar Cognitive Affective/Schmahmann Syndrome Scale. The neuropsychological data collected has to evaluate the cerebellar cognitive affective syndrome (CCAS). The CCAS consisting of cognitive and affective deficits due to cerebellar disease. | Over one year |
| To determine the cross-sectional and longitudinal variability of CSF, blood and urine biomarkers in SCAs gene mutation carriers and controls | eg. specific mutant protein dosage in CSF sample for each genotype over 1 year, if available | Over one year |
| To explore the relationship of CSF, blood and urine biomarker levels in relation to clinical and imaging markers of disease progression | Over one year |
| To assess the feedback of individuals for the disease (Most bothersome symptoms) | Evolution of a Most Bothersome Symptom (MBS) questionnaire will be performed by the physician in order to determine patients' most bothersome symptoms. This qualitative report investigating the subjective complaint and feedback of patients | Over one year |
| To assess the feedback of individuals for the disease thanks to quality of life questionnaires | Evolution of quality of life self-administrated questionnaires : Patient global impression: is a global index that may be used to rate the response of a condition EQ-5D is a standardized instrument which measures health-related quality of life that can be used in a wide range of health conditions and treatments Patient Health Questionnaire (PHQ 9) is a self-administered depression module, which scores each of the nine DSM-IV criteria as "0" (not at all) to "3" (nearly every day). | Over one year |
| To determine the cross-sectional and longitudinal variability of quantitative measures of postural stability, free walking and turning in SCA 2 and SCA 7 mutation carriers and healthy controls | Evolution of postural sway measures from the sternum and the lumbar spine by wearable APDM® sensors and evolution of cerebellar instability by Fitbit® smartwatch | Over one year |
| To determine the cross-sectional and longitudinal variability of quantitative measures of oculomotor recording in SCA 2 and SCA 7 gene mutations carriers and healthy controls. | Over one year |
| To determine the cross-sectional and longitudinal variability of optical coherence tomography in SCA 2 and SCA 7 gene mutations carriers | Over one year |
| To determine the cross-sectional and longitudinal variability of adaptative optics in SCA 2 and SCA 7 gene mutations carriers | Over one year |
| To determine the cross-sectional and longitudinal variability of autofluorescence, visual acuity, in SCA 2 and SCA 7 gene mutations carriers | Over one year |
| To determine the cross-sectional and longitudinal variability of visual field in SCA 2 and SCA 7 gene mutations carriers | Over one year |
| To determine the cross-sectional and longitudinal variability of colour contrast sensitivity in SCA 2 and SCA 7 gene mutations carriers | Over one year |
| To determine the cross-sectional and longitudinal variability of electroretinogram in SCA 2 and SCA 7 gene mutations carriers | Over one year |
| To determine the cross-sectional and longitudinal variability of static perimetry in SCA 2 and SCA 7 gene mutations carriers | Over one year |
| To determine the cross-sectional and longitudinal variability of visual evoked potential in SCA 2 and SCA 7 gene mutations carriers | Over one year |
| Result |
| Nassisi M, Coarelli G, Blanchard B, Dubec-Fleury C, Drine K, Kitic N, Sancho S, Hilab R, Tezenas du Montcel S, Junge C, Lane R, Arnold HM, Durr A, Audo I. ATXN7-Related Cone-Rod Dystrophy: The Integrated Functional Evaluation of the Cerebellum (CERMOI) Study. JAMA Ophthalmol. 2024 Apr 1;142(4):301-308. doi: 10.1001/jamaophthalmol.2024.0001. |
| D009422 |
| Nervous System Diseases |
| D013132 | Spinocerebellar Degenerations |
| D013118 | Spinal Cord Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D001259 | Ataxia |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003933 | Diagnosis |
| D003943 | Diagnostic Techniques, Neurological |
| D011677 | Punctures |
| D013812 | Therapeutics |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |