Biomarkers in Autosomal Dominant Cerebellar Ataxia

Brief Title

Biomarkers in Autosomal Dominant Cerebellar Ataxia

Official Title

Identification of Biomarkers in Patients With Autosomal Dominant Cerebellar Ataxia

Brief Summary

      Autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders that
      are clinically and genetically various. BIOSCA study aims to identify markers of the
      metabolism (energy production inside the cells) in the blood and the brain of ADCA 1,2,3 and
      7 patients and control subjects, in the perspective of future therapeutic trials.
    

Detailed Description

      Rational. Autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group
      of neurodegenerative disorders caused by unstable CAG repeat expansions encoding
      polyglutamine tracts. ADCA have a wide range of neurological symptoms including ataxia of
      gait, stance, and limbs, cerebellar dysarthria, oculomotor disturbances of cerebellar and
      supranuclear genesis, retinopathy, optic atrophy, spasticity, extra-pyramidal movement
      disorders, peripheral neuropathy, sphincter disturbances, cognitive impairment, and epilepsy.
      Corresponding to neuropathological findings in hereditary ataxia, there are three fundamental
      patterns of degeneration on MRI: spinal atrophy, olivopontocerebellar atrophy, and cortical
      cerebellar atrophy. We previously showed an hypercatabolism in premanifest and early stage
      Huntington's disease (HD), along with a systemic metabolic defect: progressive decrease of
      the plasmatic branched-chain amino acids (BCAA) - correlated with low serum IGF1
      (insulin-like growth factor 1) - and muscle energy metabolism abnormalities measured by
      31P-NMR spectroscopy. We also observed a weight loss in SCA1, 3 and mostly SCA7 patients. In
      addition, we underlined in a preliminary study a significant decrease of the BCAA in SCA1,2,3
      and 7 patients, suggesting that an energy deficit would also be implied in SCA pathogenesis.
      Transcriptional interferences are likely a part of SCA physiopathology, as shown in the
      retinal cells of a SCA7 mouse model, or as we detected over the cerebellum growth of these
      mice. The hallmark of the gene expression studies in SCA1 and SCA7 mice points out the
      implication of IGF1 pathway and IGF1 receptor. As in HD, these transcriptional disorders
      might witness the metabolic defects above-mentioned.

      Study objectives. The primary aim of the study is to provide metabolic and imaging biomarkers
      in SCA1,2,3 and 7 patients and controls in the perspective of future therapeutic trials.

      The secondary aims are to determine (i) an systemic energy profile in SCA1,2,3 and 7 patients
      with the confirmation of an hypercatabolic status, (ii) a brain energy profile in SCA1,2,3
      and 7 patients measured by in vivo 31P-NMR spectroscopy.

      Study population. BIOSCA will recruit 120 participants in the Pitie Salpetriere University
      Hospital located in Paris, France. The target cohort will be 80 patients - divided into 4
      groups of 20 participants of each mutation - and 40 controls.

      Study design. All patients (SCA1,2,3,7) will be assessed at baseline (visit 1), 1 year (visit
      2) and 2 years (visit 3). At visit 1 and 3, subjects will undergo clinical, MRI, a bone
      mineral density and a resting metabolic rate assessments, as well as donating fasted blood
      samples. Each visit will last approximately 6 hours. At visit 2, they will have only a
      clinical assessment along with a fasted blood sample. Control subjects will be seen only at
      visit 1 and 3 with the same assessments as the patients.

      Study period. BIOSCA is a prospective study for which each participant is enrolled for 24
      months. The study duration is 36 months. The start date is November 2011.

      Funding. BIOSCA is funded by a national funding hospital program in clinical research (PHRC)
      from APHP institution.
    


Study Type

Observational


Primary Outcome

metabolic biomarkers of SCA

Secondary Outcome

 imaging biomarkers of SCA

Condition

Spinocerebellar Ataxia Type 1

Intervention

metabolic and imaging biomarkers in SCA1,2,3 and 7 patients

Study Arms / Comparison Groups

 Spinocerebellar Ataxia type 1 (SCA1)
Description:  Spinocerebellar Ataxia type 1 (SCA1)

Publications

* 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

Other

Estimated Enrollment

102

Start Date

November 2011

Completion Date

December 2015

Primary Completion Date

December 2015

Eligibility Criteria

        Inclusion criteria :

          -  More than 18 years of age

          -  Ability to tolerate MRI

          -  Positive genetic test to SCA1, 2, 3 or 7

          -  Coverage by social insurance

          -  Written informed consent must be obtained from the subject

        Exclusion criteria :

          -  Less than 18 years of age

          -  Concomitant significant neurological disorder

          -  Unsuitability for MRI, e.g. claustrophobia, metal implants

          -  History of significant head injury

          -  Unability to receive an informed explanation about the protocol

          -  Unability to complete the protocol

          -  Non coverage by social insurance

          -  No written informed consent obtained
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Alexandra DURR, PhD, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT01470729

Organization ID

P100125


Responsible Party

Sponsor

Study Sponsor

Assistance Publique - Hôpitaux de Paris


Study Sponsor

Alexandra DURR, PhD, Principal Investigator, Assistance Publique - Hôpitaux de Paris


Verification Date

June 2014