Integrated Functional Evaluation of the Cerebellum

Brief Title

Integrated Functional Evaluation of the Cerebellum

Official Title

Integrated Functional Evaluation of the Cerebellum

Brief Summary

      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

Detailed Description

      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.

Study Type


Primary Outcome

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

Secondary Outcome

 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


Spinocerebellar Ataxia Type 2


Lumbar puncture

Study Arms / Comparison Groups

 SCA early-manifest and premanifest patients
Description:  This cohort is defined by individuals with a SARA score between 0 and 15 (both values included).


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

May 28, 2020

Completion Date

April 2022

Primary Completion Date

April 2022

Eligibility Criteria

        Common inclusion criteria for all participants:

          -  Ability to walk independently 30 foot without an assistive device

          -  Able to stand unassisted for 30 seconds

          -  Affiliated with the French social security, or a social security equivalent, if they
             are not French.

          -  Capacity to consent

          -  Signed Informed Consent by the subject

          -  Ability to undergo MRI scanning

        Inclusion criteria for SCA patients:

          -  Genetic diagnosis of SCA 2 or 7 (available CAG repeat length)

          -  SARA score ≤15

        Inclusion criteria for control participants:

          -  Negative Genetic diagnosis of SCA2/SCA7 available

          -  No significant neurological symptoms

          -  SARA score < 5

        Common inclusion criteria for elective participant for CSF sampling:

        • Ability to undergo a lumbar puncture

        Exclusion criteria

          -  Subjects currently receiving, or having received within 2 months prior to enrolment
             into this study, any investigational drug

          -  Pregnancy or breastfeeding

          -  Genotype consistent with other inherited ataxias

          -  Changes in coordinative physical and occupational therapy for ataxia 2 months prior to
             study participation

          -  Concomitant disorder(s) or condition(s) that affects assessment of ataxia or severity
             of ataxia during this study

          -  Contra-indications to MRI examination

          -  Person deprived of their liberty by judicial or administrative decision




18 Years - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers


Alexandra DURR, , 

Location Countries


Location Countries


Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Institut National de la Santé Et de la Recherche Médicale, France



Study Sponsor

Alexandra DURR, Principal Investigator, Institut du Cerveau - Paris Brain Institute

Verification Date

June 2021