Efficacy of Minoxidil in Children With Williams-Beuren Syndrome
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
The Williams-Beuren syndrome (WBS) is a sporadic congenital disorder characterized by a multisystem developmental impairment. This syndrome is caused by a microdeletion in chromosome 7q11.23 that encompasses loss of the elastin locus.
Elastin, which is part of the extracellular matrix, controls proliferation of vascular smooth muscle cells (VSMCs) and stabilizes arterial structure. Loss of elastin gene in WBS patients has been claimed to provide a biological basis for the abnormal elastic fibre properties leading to cardiovascular abnormalities like supravalvular aortic stenosis (SVAS), hypertension, arteriosclerosis and stenosis in more than 50% of WBS children.
These cardiovascular pathologies result in important consequences and neither curative nor preventive medicinal treatments exist at this time. Surgery is needed in more than half cases, while it is often leading to complications.
Minoxidil is a well-known antihypertensive drug used in adults and children. Furthermore, according to animal studies, minoxidil seems to increase arterial elastin content by decreasing elastase activity in these tissues. Other data demonstrate that minoxidil specifically stimulate elastin synthesis.
Working Hypothesis:If insufficient elastin synthesis leads to vascular complications and arterial hypertension in children with WBS, restoration of sufficient quantity of elastin should then result in prevention or inhibition of vascular malformations and improvement in arterial tension. Therefore, as a pharmacological agent capable to stimulate elastin expression, minoxidil might be a useful drug for the treatment of abnormal elastin metabolism in WBS children.
Objective:To evaluate the efficacy of minoxidil on cardiovascular structure in children with Williams Beuren syndrome.
Methodology: randomized controlled trial on two parallel group (23 patients in each arm) Main criterion:variation of carotid Intima-media thickness (IMT) before and after 12 months of treatment with Minoxidil versus placebo Secondary intermediate criteria of the vascular properties are arterial stiffness, cardiac and renal stenosis, arterial tension.
Total study duration:30 months including a 12 month-recruitment period
| Condition | Intervention | Phase |
|---|---|---|
|
Williams Beuren Syndrome |
Drug: Minoxidil Drug: Placebo |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | The Efficacy of Minoxidil in Children With Williams-Beuren Syndrome: a Randomized Clinical Trial. |
- Variation of carotid Intima-media thickness (IMT) before and after 12 months of treatment with Minoxidil versus placebo (vascular echography at inclusion J0, M12). [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Efficacy of minoxidil on humeral IMT (vascular echography at J0, M12 and M18) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
- Efficacy of minoxidil on arterial stiffness (pulse wave velocity and vascular compliance at J0, M12 and M18) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
- Efficacy of minoxidil on supravalvular stenosis, pulmonary stenosis, aortic stenosis and renal stenosis (cardiac and renal echodoppler at J0, and M12) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Efficacy of minoxidil on arterial tension (24H-Holter at J0 and M12) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Effect of minoxidil on neurohumoral mechanisms of cardiovascular regulation and on plasmatic markers of the extracellular matrix. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Genetic study: characterization of deletions responsible for WBS (size deletion, DNA sample at inclusion). [ Time Frame: inclusion ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 60 |
| Study Start Date: | March 2009 |
| Estimated Study Completion Date: | September 2013 |
| Estimated Primary Completion Date: | March 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
Minoxidil
|
Drug: Minoxidil
Normotension: 0.2mg/kg/day for children under 12 and 5mg/day for children aged 12 or more. Hypertension: 0.2mg/kg/day, increasing up to a maximal dosage of 1 mg/kg) for children under 12. 5mg/day, increasing as needed of 0.1 mg/kg/day (up to a maximal dosage of 40 mg/day) for children aged 12 or more. |
|
Placebo Comparator: 2
Placebo
|
Drug: Placebo
Normotension: 0.2mg/kg/day for children under 12 and 5mg/day for children aged 12 or more. Hypertension: 0.2mg/kg/day, increasing up to a maximal dosage of 1 mg/kg) for children under 12. 5mg/day, increasing as needed of 0.1 mg/kg/day (up to a maximal dosage of 40 mg/day) for children aged 12 or more. |
Eligibility| Ages Eligible for Study: | 6 Years to 18 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- proven diagnosis of Williams Beuren syndrome (genetic test)
- normotension or hypertension, treated or not
- male or female,
- 6< age <18,
- negative pregnancy test for childbearing potential female
- effective birth control for sexually active female
- signed consent form collected from parents or legal guardian
Exclusion Criteria:
- pulmonary hypertension secondary to mitral stenosis
- myocardial infarction within 1 month prior randomization
- known allergies to minoxidil or any of the components of lonoten.
- asthma
- renal failure (creatinine clearance <40ml/min)
- no affiliation to a national health insurance program (social security)
- intolerance to lactose
- current vasodilator anti hypertensive treatment
Contacts and Locations| Contact: Behrouz KASSAI, MD | 0472357551 ext +33 | behrouz.kassai-koupai@chu-lyon.fr |
| Contact: Ségolène GAILLARD | 0427857728 ext +33 | segolene.gaillard@chu-lyon.fr |
| France | |
| Service de Cardiologie Pédiatrique, CHU Angers | Not yet recruiting |
| Angers, France, 49033 | |
| Contact: Philippe PEZARD | |
| Principal Investigator: Philippe PEZARD | |
| Département de Pédiatrie, Hôpital Femme Mère Enfant | Recruiting |
| Bron, France, 69677 | |
| Contact: Pierre COCHAT | |
| Principal Investigator: Pierre COCHAT | |
| Service de Cardiologie Pédiatrique, Hôpital Cardiovasculaire L. Pradel | Recruiting |
| Bron, France, 69677 | |
| Contact: Sylvie DI FILIPPO | |
| Principal Investigator: Sylvie DI FILIPPO | |
| Service Cardiologie, CHU St Jacques | Not yet recruiting |
| Clermont-Ferrand, France, 63000 | |
| Contact: Jean René LUSSON | |
| Principal Investigator: Jean René LUSSON | |
| Département de Pédiatrie- Service de Cardiologie, CHU Grenoble | Not yet recruiting |
| Grenoble, France, 38043 | |
| Contact: Stéphanie DOUCHIN | |
| Principal Investigator: Stéphanie DOUCHIN | |
| Service des Maladies Cardiovasculaires Infantiles et Congénitales, CHRU Lille | Not yet recruiting |
| Lille, France, 59000 | |
| Contact: François GODART | |
| Principal Investigator: François GODART | |
| Service de Néphrologie Pédiatrique, CHRU de Lille | Not yet recruiting |
| Lille, France, 59000 | |
| Contact: Michel FOULARD | |
| Principal Investigator: Michel FOULARD | |
| Service de Cardiologie Infantile, CHU Nancy | Not yet recruiting |
| Nancy, France, 54511 | |
| Contact: François MARCON | |
| Principal Investigator: François MARCON | |
| Service de Physiologie, Explorations Fonctionnelles, Hôpital Robert | Not yet recruiting |
| Paris, France, 75019 | |
| Contact: André DENJEAN | |
| Principal Investigator: André DENJEAN | |
| Service de Cardiologie Pédiatrique, Hôpital Necker Enfants Malades | Not yet recruiting |
| Paris, France, 75015 | |
| Contact: Damien BONNET | |
| Principal Investigator: Damien BONNET | |
| Unité de Pharmacologie Clinique, Hôpital Robert Debré | Not yet recruiting |
| Paris, France, 75019 | |
| Contact: Evelyne JACQZ AIGRIN | |
| Principal Investigator: Evelyne JACQZ AIGRIN | |
| Service de Génétique Médicale, CHU La Milétrie | Not yet recruiting |
| Poitiers, France, 86021 | |
| Contact: Brigitte GILBERT-DUSSARDIER | |
| Principal Investigator: Brigitte GILBERT-DUSSARDIER | |
| Service de Cardiologie - Hôpital des Enfants | Not yet recruiting |
| Toulouse, France, 31059 | |
| Contact: Yves DULAC | |
| Principal Investigator: Yves DULAC | |
| Service de Néphrologie Pédiatrique - Hôpital des Enfants, CHU Toulouse | Not yet recruiting |
| Toulouse, France, 31059 | |
| Contact: Stéphane DECRAMER | |
| Principal Investigator: Stéphane DECRAMER | |
| Principal Investigator: | Behrouz KASSAI, MD | Hospices Civils de Lyon |
More Information
Additional Information:
No publications provided
| Responsible Party: | Behrouz KASSAI, CIC-EPICIM - Groupement Hospitalier Est -Hospices Civils de Lyon |
| ClinicalTrials.gov Identifier: | NCT00876200 History of Changes |
| Other Study ID Numbers: | 2006.437/30 |
| Study First Received: | April 3, 2009 |
| Last Updated: | July 21, 2011 |
| Health Authority: | France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) |
Keywords provided by Hospices Civils de Lyon:
|
Williams Beuren syndrome Cardiovascular abnormalities Cardiovascular structure |
Additional relevant MeSH terms:
|
Williams Syndrome Mental Retardation Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases Aortic Stenosis, Supravalvular Aortic Valve Stenosis Heart Valve Diseases Heart Diseases Cardiovascular Diseases |
Chromosome Disorders Congenital Abnormalities Genetic Diseases, Inborn Minoxidil Antihypertensive Agents Cardiovascular Agents Therapeutic Uses Pharmacologic Actions Vasodilator Agents |
ClinicalTrials.gov processed this record on May 16, 2013