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Biomarkers in Autosomal Dominant Cerebellar Ataxia (BIOSCA)

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ClinicalTrials.gov Identifier: NCT01470729
Recruitment Status : Completed
First Posted : November 11, 2011
Last Update Posted : December 16, 2015
Sponsor:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment
Spinocerebellar Ataxia Type 1 Spinocerebellar Ataxia Type 2 Spinocerebellar Ataxia, Autosomal Recessive 3 Episodic Ataxia, Type 7 Other: metabolic and imaging biomarkers in SCA1,2,3 and 7 patients

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 Design

Study Type : Observational
Actual Enrollment : 102 participants
Time Perspective: Prospective
Official Title: Identification of Biomarkers in Patients With Autosomal Dominant Cerebellar Ataxia
Study Start Date : November 2011
Primary Completion Date : December 2015
Study Completion Date : December 2015


Groups and Cohorts

Group/Cohort Intervention/treatment
Spinocerebellar Ataxia type 1 (SCA1)
Spinocerebellar Ataxia type 1 (SCA1)
Other: metabolic and imaging biomarkers in SCA1,2,3 and 7 patients
MRI, a bone mineral density and a resting metabolic rate assessments, as well as donating fasted blood samples
Spinocerebellar Ataxia type 2 (SCA2)
Spinocerebellar Ataxia type 2 (SCA2)
Other: metabolic and imaging biomarkers in SCA1,2,3 and 7 patients
MRI, a bone mineral density and a resting metabolic rate assessments, as well as donating fasted blood samples
Spinocerebellar Ataxia type 3 (SCA3)
Spinocerebellar Ataxia type 3 (SCA3)
Other: metabolic and imaging biomarkers in SCA1,2,3 and 7 patients
MRI, a bone mineral density and a resting metabolic rate assessments, as well as donating fasted blood samples
Spinocerebellar Ataxia type 7 (SCA7)
Spinocerebellar Ataxia type 7 (SCA7)
Other: metabolic and imaging biomarkers in SCA1,2,3 and 7 patients
MRI, a bone mineral density and a resting metabolic rate assessments, as well as donating fasted blood samples


Outcome Measures

Primary Outcome Measures :
  1. metabolic biomarkers of SCA [ Time Frame: 12 months or 24 months ]

Secondary Outcome Measures :
  1. imaging biomarkers of SCA [ Time Frame: 24 months ]

Biospecimen Retention:   Samples With DNA
blood

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Spinocerebellar Ataxia Type 1 (SCA1) Spinocerebellar Ataxia Type 2 (SCA2) Spinocerebellar Ataxia Type 3 (SCA3) Spinocerebellar Ataxia Type 7 (SCA7)
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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01470729


Locations
France
Groupe Hospitalier Pitié Salpêtrière
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Alexandra DURR, PhD Assistance Publique - Hôpitaux de Paris
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01470729     History of Changes
Other Study ID Numbers: P100125
First Posted: November 11, 2011    Key Record Dates
Last Update Posted: December 16, 2015
Last Verified: June 2014

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Spinocerebellar ataxia, energy metabolism, NMR spectroscopy

Additional relevant MeSH terms:
Spinocerebellar Ataxias
Spinocerebellar Degenerations
Ataxia
Cerebellar Ataxia
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn