Efficacy of Minoxidil in Children With Williams-Beuren Syndrome

Williams Beuren Syndrome Clinical Trial

— Williams  

Official title:

The Efficacy of Minoxidil in Children With Williams-Beuren Syndrome: a Randomized Clinical Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00876200
• Other study ID #: 2006.437/30
• Status: Completed
• Phase: Phase 2
• Start date: March 2009
• Est. completion date: August 2015

Study information

• Verified date: January 2016
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: August 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Syndrome
• Williams Beuren Syndrome
• Williams Syndrome

Intervention

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
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.

Locations

Country	Name	City	State
France	Service de Cardiologie Pédiatrique, CHU Angers	Angers
France	Service de Cardiologie, Hôpital Saint-André, CHU Bordeaux	Bordeaux
France	Service de Génétique Médicale, Hôpital Pellegrin, CHU Bordeaux	Bordeaux
France	Service de Néphrologie Pédiatrique, Hôpital Pellegrin, CHU Bordeaux	Bordeaux
France	Département de Pédiatrie, Hôpital Femme Mère Enfant	Bron
France	Service de Cardiologie Pédiatrique, Hôpital Cardiovasculaire L. Pradel	Bron
France	Service Cardiologie, CHU St Jacques	Clermont-Ferrand
France	Département de Pédiatrie- Service de Cardiologie, CHU Grenoble	Grenoble
France	Service de Néphrologie Pédiatrique, CHRU de Lille	Lille
France	Service des Maladies Cardiovasculaires Infantiles et Congénitales, CHRU Lille	Lille
France	Service de Cardiologie Infantile, CHU Nancy	Nancy
France	Service de Cardiologie Pédiatrique, Hôpital Necker Enfants Malades	Paris
France	Service de Physiologie, Explorations Fonctionnelles, Hôpital Robert Debré	Paris
France	Unité de Pharmacologie Clinique, Hôpital Robert Debré	Paris
France	Service de Pathologie Cardiaque Congénitale du Fœtus, de l'Enfant et de l'Adulte, Hôpital Haut Lévêque, CHU de Bordeaux	Pessac
France	Service de Génétique Médicale, CHU La Milétrie	Poitiers
France	Service de Cardiologie - Hôpital des Enfants	Toulouse
France	Service de Néphrologie Pédiatrique - Hôpital des Enfants, CHU Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Variation of Carotid Intima-media Thickness (IMT) Assessed by Vascular Echography		12 months
Secondary	Efficacy of Minoxidil on Humeral IMT Assessed by Vascular Echography		18 months
Secondary	Efficacy of Minoxidil on Arterial Stiffness (Pulse Wave Velocity and Vascular Compliance at J0, M12 and M18)		18 months
Secondary	Efficacy of Minoxidil on Supravalvular Stenosis, Pulmonary Stenosis, Aortic Stenosis and Renal Stenosis (Cardiac and Renal Echodoppler at J0, and M12)		12 months
Secondary	Efficacy of Minoxidil on Arterial Tension (24H-Holter at J0 and M12)		12 months
Secondary	Effect of Minoxidil on Neurohumoral Mechanisms of Cardiovascular Regulation and on Plasmatic Markers of the Extracellular Matrix.		12 months
Secondary	Genetic Study: Characterization of Deletions Responsible for WBS (Size Deletion, DNA Sample at Inclusion).		Day 0

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