Efficacy of Minoxidil in Children With Williams-Beuren Syndrome
Condition: Williams Beuren Syndrome
MeSH terms: Williams Syndrome; Syndrome
Study type: Interventional
Phase: Phase 2

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
    


Intervention name(s): Minoxidil; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.
Intervention MeSH terms: Minoxidil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Williams Beuren syndrome; Cardiovascular abnormalities; Cardiovascular structure