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Trial record 1 of 12 for:    CADASIL
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Generation of a Cellular Model of CADASIL From Skin Fibroblasts

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ClinicalTrials.gov Identifier: NCT02032225
Recruitment Status : Enrolling by invitation
First Posted : January 9, 2014
Last Update Posted : December 7, 2016
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France

Brief Summary:

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 or disease Intervention/treatment
CADASIL Other: Skin biopsy

Study Type : Observational
Estimated Enrollment : 10 participants
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
Study Start Date : February 2014
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2018

Group/Cohort Intervention/treatment
patients with CADASIL
Other: Skin biopsy

Primary Outcome Measures :
  1. Derivation of iPS cells from skin biopsies of patients with CADASIL [ Time Frame: 30 months ]

Secondary Outcome Measures :
  1. Differentiation of iPS cells to vascular smooth muscle cells, phenotypic and mechanistic analyses [ Time Frame: 24 mois ]
    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.

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Ages Eligible for Study:   30 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
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)

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 ) .

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): NCT02032225

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

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 ( Registry Identifier: IDRCB )
First Posted: January 9, 2014    Key Record Dates
Last Update Posted: December 7, 2016
Last Verified: December 2016

Additional relevant MeSH terms:
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
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, Inborn
Cerebral Infarction
Brain Infarction
Brain Ischemia
Neurocognitive Disorders
Mental Disorders