Trial record 5 of 6 for:    "williams syndrome"

Efficacy of Minoxidil in Children With Williams-Beuren Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Hospices Civils de Lyon
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT00876200
First received: April 3, 2009
Last updated: January 14, 2014
Last verified: January 2014
  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.

Resource links provided by NLM:


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: 46
Study Start Date: March 2009
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: March 2014 (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
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: 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 Recruiting
Angers, France, 49033
Contact: Philippe PEZARD         
Principal Investigator: Philippe PEZARD         
Service de Néphrologie Pédiatrique, Hôpital Pellegrin, CHU Bordeaux Recruiting
Bordeaux, France, 33076
Contact: Brigitte LLANAS, MD         
Principal Investigator: Brigitte LLANAS, MD         
Service de Génétique Médicale, Hôpital Pellegrin, CHU Bordeaux Recruiting
Bordeaux, France
Contact: Marie-Ange DELRUE, MD         
Principal Investigator: Marie-Ange DELRUE, MD         
Service de Cardiologie, Hôpital Saint-André, CHU Bordeaux Recruiting
Bordeaux, France, 33075
Contact: Philippe GOSSE, MD         
Principal Investigator: Philippe GOSSE, MD         
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 Recruiting
Clermont-Ferrand, France, 63000
Contact: Jean René LUSSON         
Principal Investigator: Jean René LUSSON         
Département de Pédiatrie- Service de Cardiologie, CHU Grenoble Recruiting
Grenoble, France, 38043
Contact: Stéphanie DOUCHIN         
Principal Investigator: Stéphanie DOUCHIN         
Service des Maladies Cardiovasculaires Infantiles et Congénitales, CHRU Lille Recruiting
Lille, France, 59000
Contact: François GODART         
Principal Investigator: François GODART         
Service de Néphrologie Pédiatrique, CHRU de Lille Recruiting
Lille, France, 59000
Contact: Michel FOULARD         
Principal Investigator: Michel FOULARD         
Service de Cardiologie Infantile, CHU Nancy Recruiting
Nancy, France, 54511
Contact: François MARCON         
Principal Investigator: François MARCON         
Service de Physiologie, Explorations Fonctionnelles, Hôpital Robert Recruiting
Paris, France, 75019
Contact: André DENJEAN         
Principal Investigator: André DENJEAN         
Service de Cardiologie Pédiatrique, Hôpital Necker Enfants Malades Recruiting
Paris, France, 75015
Contact: Damien BONNET         
Principal Investigator: Damien BONNET         
Unité de Pharmacologie Clinique, Hôpital Robert Debré Recruiting
Paris, France, 75019
Contact: Evelyne JACQZ AIGRIN         
Principal Investigator: Evelyne JACQZ AIGRIN         
Service de Pathologie Cardiaque Congénitale du Fœtus, de l'Enfant et de l'Adulte, Hôpital Haut Lévêque, CHU de Bordeaux Recruiting
Pessac, France, 33604
Contact: Jean Benoit THAMBO, MD         
Principal Investigator: Jean-Benoît THAMBO, MD         
Service de Génétique Médicale, CHU La Milétrie Recruiting
Poitiers, France, 86021
Contact: Brigitte GILBERT-DUSSARDIER         
Principal Investigator: Brigitte GILBERT-DUSSARDIER         
Service de Néphrologie Pédiatrique - Hôpital des Enfants, CHU Toulouse Recruiting
Toulouse, France, 31059
Contact: Stéphane DECRAMER         
Principal Investigator: Stéphane DECRAMER         
Service de Cardiologie - Hôpital des Enfants Recruiting
Toulouse, France, 31059
Contact: Yves DULAC         
Principal Investigator: Yves DULAC         
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Principal Investigator: Behrouz KASSAI, MD Hospices Civils de Lyon
  More Information

Additional Information:
No publications provided

Responsible Party: 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: January 14, 2014
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 July 10, 2014