Minoxidil versus placebo in the treatment of arterial wall hypertrophy in children with Williams Beuren Syndrome: a randomized controlled trial

Abstract

Background Insufficient elastin synthesis leads to vascular complications and arterial hypertension in children with Williams-Beuren syndrome. Restoring sufficient quantity of elastin should then result in prevention or inhibition of vascular malformations and improvement in arterial blood pressure. Methods The aim of this study was to assess the efficacy and safety of minoxidil on Intima Media Thickness (IMT) on the right common carotid artery after twelve-month treatment in patient with Williams-Beuren syndrome. We performed a randomized placebo controlled double blind trial. All participants were treated for 12 months and followed for 18 months. The principal outcome was assessed by an independent adjudication committee blinded to the allocated treatment groups. Results The principal outcome was available for 9 patients in the placebo group and 8 patients in the minoxidil group. After 12-month treatment, the IMT in the minoxidil group increased by 0.03 mm (95% CI -0.002, 0.06) compared with 0.01 mm (95%CI - 0.02, 0.04 mm) in the placebo group ( p = 0.4). Two serious adverse events unrelated to the treatment occurred, one in the minoxidil and 1 in the placebo group. After 18 months, the IMT increased by 0.07 mm (95% CI 0.04, 0.10 mm) in the minoxidil compared with 0.01 mm (95% CI -0.02, 0.04 mm) in the placebo group ( p = 0.008). Conclusion Our results suggest a slight increase after 12 and 18-month follow-up in IMT. More understanding of the biological changes induced by minoxidil should better explain its potential role on elastogenesis in Williams-Beuren syndrome. Trials registration US National Institutes of Health Clinical Trial Register (NCT00876200). Registered 3 April 2009 (retrospectively registered). Electronic supplementary material The online version of this article (10.1186/s12887-019-1544-1) contains supplementary material, which is available to authorized users.

Systemic Minoxidil Accidental Exposure in a Paediatric Population: A Case Series Study of Cutaneous and Systemic Side Effects

“…The mentioned studies agree on the possible side effects of minoxidil in paediatric population, hypertrichosis is the most common, and fluid retention, arrhythmia, electrocardiogram alterations and pericarditis are some of the most severe [ 13 , 14 , 15 , 16 , 17 , 18 ].…”

“…However, there are reports of systemic toxicity in children due to percutaneous absorption of topical minoxidil [ 14 ]. Regarding oral minoxidil and children the current scientific evidence is limited to a report of the accidental ingestion of minoxidil [ 14 ], a randomized clinical trial with 9 patients receiving oral minoxidil treatment for arterial wall hypertrophy for Williams–Beuren syndrome [ 15 ], and some case series about the use of oral minoxidil for refractory hypertension in children [ 16 , 17 , 18 ]. In addition, a recently published systematic review [ 4 ] addressed the issue of minoxidil and children, finding only reports of topical minoxidil in children and one report of low-dose oral minoxidil in a 11-years-old female.…”

“…The initial dose of oral minoxidil in paediatric population regarding the treatment of hypertension is 0.1–0.2 mg/kg/day. It may be increase up to 1 mg/kg/day depending on the tolerance and effectiveness of the treatment [ 15 , 20 ]. When used to treat loose anagen hair syndrome [ 19 ], dose administered was lower than 0.02mg/kg/day.…”

“…When used to treat loose anagen hair syndrome [ 19 ], dose administered was lower than 0.02mg/kg/day. Severe adverse events seem to be dose-dependent, with a positive gradient [ 13 , 14 , 15 , 16 , 17 , 18 ]. However, most of these studies have a small sample size and none of them focus on the onset, latency, location and evolution of hypertrichosis.…”

Elastic fibers in orthopedics: Form and function in tendons and ligaments, clinical implications, and future directions

“…Pharmacologic therapy has also shown promise. Several studies demonstrated that the antihypertensive medication minoxidil stimulates elastic fiber synthesis, improves the function of existing fibers, and decreases fiber degradation [108][109][110]. These synergistic effects are hypothesized to explain the reversal of age-related arterial changes reported in murine models 110.…”