Efficacy of Minoxidil in Children With Williams-Beuren Syndrome

Brief Title

Efficacy of Minoxidil in Children With Williams-Beuren Syndrome

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 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

Study Phase

Phase 2

Study Type


Primary Outcome

Variation of Carotid Intima-media Thickness (IMT) Assessed by Vascular Echography

Secondary Outcome

 Efficacy of Minoxidil on Humeral IMT Assessed by Vascular Echography


Williams Beuren Syndrome



Study Arms / Comparison Groups

Description:  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.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

March 2009

Completion Date

August 2015

Primary Completion Date

February 2015

Eligibility Criteria

        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




6 Years - 18 Years

Accepts Healthy Volunteers



Behrouz KASSAI, MD, , 

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Hospices Civils de Lyon

Study Sponsor

Behrouz KASSAI, MD, Principal Investigator, Hospices Civils de Lyon

Verification Date

January 2016