Efficacy of Minoxidil in Children With Williams-Beuren Syndrome - Full Text View

Sponsor:	Hospices Civils de Lyon
Information provided by:	Hospices Civils de Lyon
ClinicalTrials.gov Identifier:	NCT00876200

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 II

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.

Resource links provided by NLM:

Genetics Home Reference related topics: 17q21.31 microdeletion syndrome tetrasomy 18p Williams syndrome

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Minoxidil

U.S. FDA Resources

Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00876200

Contacts

Contact: Behrouz KASSAI, MD	0472357551 ext +33	behrouz.kassai-koupai@chu-lyon.fr
Contact: Ségolène GAILLARD	0427857728 ext +33	segolene.gaillard@chu-lyon.fr

Locations

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

Sponsors and Collaborators

Hospices Civils de Lyon

Investigators

Principal Investigator:

Behrouz KASSAI, MD

Hospices Civils de Lyon

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

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 - French Health Products Safety Agency

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 February 09, 2012