Division of Child Adolescent Neurology, Department of Pediatrics, University of Texas Medical School at Houston, Houston, TX 77030, USA.
Drugs R D. 2012 Sep 1;12(3):121-6. doi: 10.2165/11634580-000000000-00000.
Facial angiofibromas are disfiguring facial lesions, present in up to 80% of patients with tuberous sclerosis complex. Recent elucidation of the complex cell signaling pathways that are disrupted in tuberous sclerosis indicates that rapamycin may be successful in alleviating the appearance of these lesions. The objectives of the current study were to evaluate the safety of topically applied rapamycin in patients with tuberous sclerosis complex and to determine its potential effectiveness in treatment of facial angiofibromas.
The study was a prospective, randomized, double-blind, placebo-controlled study performed at the University of Texas Health Science Center at Houston. Study subjects were recruited from the patient populations at the University of Texas Tuberous Sclerosis Center of Excellence. All subjects were over the age of 13 years and had a diagnosis of tuberous sclerosis complex. Subjects were excluded if they were using any form of rapamycin or if they were pregnant. Study subjects applied the study product to their facial angiofibromas nightly for a duration of 6 months. The investigational product contained one of three doses of rapamycin compounded with Skincerity®: (i) no rapamycin; (ii) 1 mg of rapamycin per 30 cc (0.003%); or (iii) 5 mg of rapamycin per 30 cc (0.015%). Plasma rapamycin concentrations were measured monthly to test for systemic absorption. Complete blood counts were performed monthly to test for anemia, neutropenia, or thrombocytopenia. Upon completion of the trial, subjects were asked if the formulation had improved the appearance of their facial angiofibromas.
Twenty-three subjects completed the study. There was no detectable systemic absorption of rapamycin (all blood concentrations were <1.0 ng/mL). There were no significant changes in white blood cell, red blood cell, or platelet counts. Seventy-three percent of subjects in the treatment arms versus 38% of subjects in the placebo arm reported a subjective improvement in the appearance of their facial angiofibromas.
The application of low-dose topical rapamycin (0.003-0.015%) to the face can safely decrease the appearance of facial angiofibromas in patients with tuberous sclerosis complex.
ClinicalTrials.gov Identifier: NCT01031901.
面部血管纤维瘤是一种毁容性的面部病变，在 80%的结节性硬化症患者中存在。最近阐明的结节性硬化症中被打乱的复杂细胞信号通路表明，雷帕霉素可能成功地缓解这些病变的外观。本研究的目的是评估局部应用雷帕霉素在结节性硬化症患者中的安全性，并确定其在治疗面部血管纤维瘤中的潜在有效性。
该研究是在德克萨斯大学休斯顿健康科学中心进行的一项前瞻性、随机、双盲、安慰剂对照研究。研究对象是从德克萨斯大学结节性硬化症卓越中心的患者人群中招募的。所有受试者年龄均超过 13 岁，且被诊断为结节性硬化症。如果患者正在使用任何形式的雷帕霉素或怀孕，则将其排除在外。研究对象每晚将研究产品涂抹在面部血管纤维瘤上，持续 6 个月。研究产品含有三种雷帕霉素浓度之一，与 Skincerity®混合：（i）不含雷帕霉素；（ii）每 30 毫升含 1 毫克雷帕霉素（0.003%）；或（iii）每 30 毫升含 5 毫克雷帕霉素（0.015%）。每月测量血浆雷帕霉素浓度以检测全身吸收情况。每月进行全血细胞计数以检测贫血、中性粒细胞减少或血小板减少。试验完成后，询问受试者该制剂是否改善了他们面部血管纤维瘤的外观。
23 名受试者完成了研究。未检测到雷帕霉素的全身吸收（所有血液浓度均<1.0ng/mL）。白细胞、红细胞或血小板计数无显著变化。治疗组中有 73%的受试者报告面部血管纤维瘤的外观有主观改善，而安慰剂组中仅有 38%的受试者报告有改善。
将低剂量局部雷帕霉素（0.003-0.015%）应用于面部可安全减少结节性硬化症患者面部血管纤维瘤的外观。
ClinicalTrials.gov 标识符：NCT01031901。
