CADASILNCT02032225
Generation of a Cellular Model of CADASIL From Skin Fibroblasts
An observational study of CADASIL, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 60 years
- Conditions the study is for
- CADASIL
- What is being tested?
- Skin biopsy
- How many people
- 8 participants
- Where
- 1 siteFrance
- Study dates
- Feb 2014to 11 Feb 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 60 years
- All sexes
- No healthy volunteers
- Adult
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)
Who may be able to join
- 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.
Who cannot join
- 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 ) .
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Obtention d'un modèle Cellulaire de la Maladie CADASIL à Partir de Fibroblastes cutanés de Patients
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.
- Conditions
- CADASIL
- Being tested
- Skin biopsy
- Medical subject headings
- CADASIL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Skin biopsyOther
| Study group | Role | What they receive |
|---|---|---|
| CADASIL | patients with CADASIL Receives: Other: Skin biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Derivation of iPS cells from skin biopsies of patients with CADASIL
Measured: 30 months
Secondary outcomes (1)
Differentiation of iPS cells to vascular smooth muscle cells, phenotypic and mechanistic analyses
Differentiation of iPS cells to vascular smooth muscle cells and phenotypic analysis (12 mois) Mechanistic analyses (12 mois)
Measured: 24 mois
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2014 (estimated)
- Study startFeb 2014
- Primary completion11 Feb 2015
- Study completion11 Feb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CADASILStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Anne JOUTEL, MD, PhD, Principal investigator, Institut National de la Santé Et de la Recherche Médicale, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02032225
- Sponsor's protocol ID
- C13-34
- Other IDs
- 2013-A00994-41
- Status last verified
- Dec 2016
- First submitted
- 3 Jan 2014
- Last updated
- 16 May 2025
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Obtention d'un modèle Cellulaire de la Maladie CADASIL à Partir de Fibroblastes cutanés de Patients
- ClinicalTrials.gov ID
- NCT02032225
- Acronym / sponsor ID
- C13-34
- Conditions
- CADASIL
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Study start
- Feb 2014
- Primary completion
- 11 Feb 2015 (actual)
- Study completion
- 11 Feb 2015 (actual)
- First posted
- 9 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CADASIL | – | Other: Skin biopsypatients with CADASIL |
Who may qualify
- Ages
- 30 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- 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)
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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 ) .
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Skin biopsy | Other | CADASIL |
Primary outcome
Derivation of iPS cells from skin biopsies of patients with CADASIL
Time frame: 30 months
1 secondary outcome
Differentiation of iPS cells to vascular smooth muscle cells, phenotypic and mechanistic analyses
Time frame: 24 mois
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2025.
Related trials for CADASIL
RecruitingObservational study
Registry for CADASIL
Cerebral Autosomal Dominant Ateriopathy With Subcortical Infarcts and Leukoencephalopathy
RecruitingObservational study
Natural History Study of CADASIL
Cardiovascular Disease, Arterial Stiffness
RecruitingObservational study
The Erlanger Stroke Registry (ESPro) is the Only Ongoing Prospective Population-based Stroke Registry in Germany, Started in 1994. ESPro Includes All Hospitalized and Non-hospitalized Patients With Stroke in the Community of Erlangen (120.000 Inhabitants), With a Long-life Follow-up.
Intracerebral Haemorrhage (ICH), Cerebral Infarction
Active, not recruitingObservational study
Florida Cerebrovascular Disease Biorepository and Genomics Center
Cerebrovascular Disease, Ischemic Stroke
RecruitingObservational study
Effect of the Mediterranean Diet in Patients Affected by CADASIL and Cerebral Amyloid Angiopathy.
Cerebral Amyloid Angiopathy, CAA - Cerebral Amyloid Angiopathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne JOUTEL, MD, PhD principal investigator
Institut National de la Santé Et de la Recherche Médicale, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of CADASIL, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Derivation of iPS cells from skin biopsies of patients with CADASIL (time frame: 30 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2025.