Efficacy of Minoxidil in Children With Williams-Beuren Syndrome
Williams
The Efficacy of Minoxidil in Children With Williams-Beuren Syndrome: a Randomized Clinical Trial.
1 other identifier
interventional
21
1 country
18
Brief 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Mar 2009
Longer than P75 for phase_2
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2009
CompletedFirst Submitted
Initial submission to the registry
April 3, 2009
CompletedFirst Posted
Study publicly available on registry
April 6, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2015
CompletedResults Posted
Study results publicly available
July 26, 2019
CompletedSeptember 30, 2025
January 1, 2016
5.9 years
April 3, 2009
February 14, 2019
September 9, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Variation of Carotid Intima-media Thickness (IMT) Assessed by Vascular Echography
12 months
Secondary Outcomes (6)
Efficacy of Minoxidil on Humeral IMT Assessed by Vascular Echography
18 months
Efficacy of Minoxidil on Arterial Stiffness (Pulse Wave Velocity and Vascular Compliance at J0, M12 and M18)
18 months
Efficacy of Minoxidil on Supravalvular Stenosis, Pulmonary Stenosis, Aortic Stenosis and Renal Stenosis (Cardiac and Renal Echodoppler at J0, and M12)
12 months
Efficacy of Minoxidil on Arterial Tension (24H-Holter at J0 and M12)
12 months
Effect of Minoxidil on Neurohumoral Mechanisms of Cardiovascular Regulation and on Plasmatic Markers of the Extracellular Matrix.
12 months
- +1 more secondary outcomes
Study Arms (2)
Minoxidil
EXPERIMENTALNormotension: 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
PLACEBO COMPARATORPlacebo = lactose
Interventions
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.
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 Criteria
You may qualify if:
- proven diagnosis of Williams Beuren syndrome (genetic test)
- normotension or hypertension, treated or not
- male or female,
- \< 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
Service de Cardiologie Pédiatrique, CHU Angers
Angers, 49033, France
Service de Cardiologie, Hôpital Saint-André, CHU Bordeaux
Bordeaux, 33075, France
Service de Néphrologie Pédiatrique, Hôpital Pellegrin, CHU Bordeaux
Bordeaux, 33076, France
Service de Génétique Médicale, Hôpital Pellegrin, CHU Bordeaux
Bordeaux, France
Département de Pédiatrie, Hôpital Femme Mère Enfant
Bron, 69677, France
Service de Cardiologie Pédiatrique, Hôpital Cardiovasculaire L. Pradel
Bron, 69677, France
Service Cardiologie, CHU St Jacques
Clermont-Ferrand, 63000, France
Département de Pédiatrie- Service de Cardiologie, CHU Grenoble
Grenoble, 38043, France
Service de Néphrologie Pédiatrique, CHRU de Lille
Lille, 59000, France
Service des Maladies Cardiovasculaires Infantiles et Congénitales, CHRU Lille
Lille, 59000, France
Service de Cardiologie Infantile, CHU Nancy
Nancy, 54511, France
Service de Cardiologie Pédiatrique, Hôpital Necker Enfants Malades
Paris, 75015, France
Service de Physiologie, Explorations Fonctionnelles, Hôpital Robert Debré
Paris, 75019, France
Unité de Pharmacologie Clinique, Hôpital Robert Debré
Paris, 75019, France
Service de Pathologie Cardiaque Congénitale du Fœtus, de l'Enfant et de l'Adulte, Hôpital Haut Lévêque, CHU de Bordeaux
Pessac, 33604, France
Service de Génétique Médicale, CHU La Milétrie
Poitiers, 86021, France
Service de Cardiologie - Hôpital des Enfants
Toulouse, 31059, France
Service de Néphrologie Pédiatrique - Hôpital des Enfants, CHU Toulouse
Toulouse, 31059, France
Related Publications (1)
Kassai B, Bouye P, Gilbert-Dussardier B, Godart F, Thambo JB, Rossi M, Cochat P, Chirossel P, Luong S, Serusclat A, Canterino I, Mercier C, Rabilloud M, Pivot C, Pirot F, Ginhoux T, Coopman S, Grenet G, Gueyffier F, Di-Fillippo S, Bertholet-Thomas A. Minoxidil versus placebo in the treatment of arterial wall hypertrophy in children with Williams Beuren Syndrome: a randomized controlled trial. BMC Pediatr. 2019 May 28;19(1):170. doi: 10.1186/s12887-019-1544-1.
PMID: 31138170RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr Behrouz KASSAI-KOUPAI
- Organization
- Hospices Civils de Lyon
Study Officials
- PRINCIPAL INVESTIGATOR
Behrouz KASSAI, MD
Hospices Civils de Lyon
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 3, 2009
First Posted
April 6, 2009
Study Start
March 1, 2009
Primary Completion
February 1, 2015
Study Completion
August 1, 2015
Last Updated
September 30, 2025
Results First Posted
July 26, 2019
Record last verified: 2016-01