Trial record 1 of 8 for:    CADASIL
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Generation of a Cellular Model of CADASIL From Skin Fibroblasts

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier:
NCT02032225
First received: January 3, 2014
Last updated: January 7, 2014
Last verified: January 2014
  Purpose

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL) is an archetypal small vessel disease of the brain caused by dominant mutations in the NOTCH3 receptor. Cardinal vascular lesions include deposition of granular osmiophilic material (GOM) within the basal lamina of smooth muscle cells, progressive smooth muscle cell loss, and fibrosis of the media. Pathogenic mutations alter the number of cysteine residues in the extracellular domain of NOTCH3 (Notch3 ECD), leading to its abnormal accumulation in the GOM deposits. Vascular smooth muscle cell has been identified as the primary target cell in this disease. Pathophysiological processes leading from NOTCH3 mutations to smooth muscle cell loss remain poorly understood.

The investigators propose to study these mechanisms by reprogramming skin cells to become stem cells and then differentiating them to vascular smooth muscle cells.

The hypothesis of this study is that the differentiated smooth muscle cells will display the characteristic features of CADASIL, ie, Notch3 ECD accumulation and GOM deposits.


Condition Intervention
CADASIL
Other: Skin biopsy

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Obtention d'un modèle Cellulaire de la Maladie CADASIL à Partir de Fibroblastes cutanés de Patients

Resource links provided by NLM:


Further study details as provided by Institut National de la Santé Et de la Recherche Médicale, France:

Primary Outcome Measures:
  • Derivation of iPS cells from skin biopsies of patients with CADASIL [ Time Frame: 30 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Differentiation of iPS cells to vascular smooth muscle cells, phenotypic and mechanistic analyses [ Time Frame: 24 mois ] [ Designated as safety issue: No ]
    Differentiation of iPS cells to vascular smooth muscle cells and phenotypic analysis (12 mois) Mechanistic analyses (12 mois)


Biospecimen Retention:   Samples Without DNA

Skin biopsies will be collected to derive fibroblasts. These will be retained and reprogrammed to iPS cells (also to be retained). iPS cells will be differentiated in vascular smooth muscle cells.


Estimated Enrollment: 10
Study Start Date: February 2014
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
CADASIL
patients with CADASIL
Other: Skin biopsy

  Eligibility

Ages Eligible for Study:   30 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

patients with CADASIL managed at the reference centre for rare vascular diseases of the central nervous system and the retina (CERVCO) (Lariboisière Hospital, Paris, France)

Criteria

Inclusion Criteria :

  • Between 30 and 60 years;
  • Having a social security scheme or, CMU ;
  • Diagnosis of CADASIL confirmed by molecular analysis performed previously (missense mutation in the Notch3 gene affecting the number of cysteine ​​in one of the 34 EGFR of NOTCH3 ) ;
  • No countra-indication for a skin biopsy (ongoing treatment with anti-coagulant, history of bleeding disorder or deficiency of blood clotting factors) ;
  • Written consent given.

Exclusion Criteria :

  • Patients without social security scheme or, CMU ;
  • Patients aged under 30 or over 60 years at the time of the first visit ;
  • Pregnant women beyond the 5th month of pregnancy
  • Patients who are not able to give informed consent ;
  • Countra-indication to the achievement of the skin biopsy ( ongoing treatment with anti- coagulant, history of bleeding disorder or deficiency of coagulation factors ) .
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02032225

Locations
France
INSERM
Paris, France, 75010
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
Principal Investigator: Anne JOUTEL, MD, PhD Institut National de la Santé Et de la Recherche Médicale, France
  More Information

No publications provided

Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier: NCT02032225     History of Changes
Other Study ID Numbers: C13-34, 2013-A00994-41
Study First Received: January 3, 2014
Last Updated: January 7, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Additional relevant MeSH terms:
CADASIL
Dementia, Multi-Infarct
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia, Vascular
Cerebral Arterial Diseases
Intracranial Arterial Diseases
Dementia
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, Inborn
Cerebral Infarction
Brain Infarction
Brain Ischemia
Stroke
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 26, 2014