Efficacy of Minoxidil in Children With Williams-Beuren Syndrome

Trial end date:
Target enrollment:
Participant gender:
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
Phase 2
Accepts Healthy Volunteers?
Lead Sponsor:
Hospices Civils de Lyon
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