Clinical Trial: Efficacy of Minoxidil in Children With Williams-Beuren Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 efficac

Detailed Summary:
Sponsor: Hospices Civils de Lyon

Current Primary Outcome: 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 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Efficacy of minoxidil on humeral IMT (vascular echography at J0, M12 and M18) [ Time Frame: 18 months ]
  • Efficacy of minoxidil on arterial stiffness (pulse wave velocity and vascular compliance at J0, M12 and M18) [ Time Frame: 18 months ]
  • 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 ]
  • Efficacy of minoxidil on arterial tension (24H-Holter at J0 and M12) [ Time Frame: 12 months ]
  • Effect of minoxidil on neurohumoral mechanisms of cardiovascular regulation and on plasmatic markers of the extracellular matrix. [ Time Frame: 12 months ]
  • Genetic study: characterization of deletions responsible for WBS (size deletion, DNA sample at inclusion). [ Time Frame: inclusion ]


Original Secondary Outcome: Same as current

Information By: Hospices Civils de Lyon

Dates:
Date Received: April 3, 2009
Date Started: March 2009
Date Completion:
Last Updated: January 20, 2016
Last Verified: January 2016