efficacy and safety study of topical rapamycin associated with pulsed dye laser in patients with sturge-weber syndrome

Conditions: Sturge- Weber Syndrome

Summary: sturge-weber syndrome (sws) is a rare congenital neuro-cutaneous disorder considered as a rare or orphan disease. sws is characterized by a capillary vascular malformation (cm) localized on the skin of the face, eyes and central nervous system. given the localization and the extent of the cm, children with sws are particularly prone to developing severe psychological problems. the standard treatment for cm is pulsed dye laser (pdl) although in these cases whitening of the lesion is rarely achieved. combining topical rapamycin, a specific inhibitor of the mammalian target of rapamycin, with pdl is hypothesised to be a good therapeutic option in these patients.

patients with sws will be treated with 2 sessions of pdl in the lateral part of the cm separated by an interval of 6 weeks and with 1% topical rapamycin or placebo in the superior or inferior half, both applied once a day for 12 weeks. the clinical response will be analyzed using a morphologic and chromatographic computerised system and with spectrometry. histological response will be evaluated also. for that purpose, we will make 4 biopsies, one in each quadrant (quadrant treated with pdl and placebo, quadrant treated with pdl and rapamycin, quadrant treated only with rapamycin and quadrant treated only with placebo)

Eligibility criteria:
inclusion criteria: * diagnosis: all patients must have the diagnostic criteria for sturge-weber syndrome. * age: patients must be greater than 16 years and less than or equal to 21 years of age at the time of study entry. * capillary malformation: patients must have cm on the face. * investigational drug: patients must not have received an investigational drug within 3 months. * females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during the time they are receiving the study drug and for 3 months thereafter. abstinence is an acceptable method of birth control. women of childbearing potential will be given a pregnancy test prior to administration of rapamycin and must have a negative pregnancy test. * intellectual capacity to understand the information given and able to comply with the protocol and safety monitoring requirements of the study in the opinion of the investigator. * signed informed consent/assent. exclusion criteria: * patients with diagnosis of sturge-weber syndrome without facial cm. * patients with another cutaneous disease on the cm area. * patients that will be applying another topical cream on the cm area. * chronic treatment with systemic steroids or another immunosuppressive agent. patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary. * patients who: * have had a major surgery or significant traumatic injury within 2 weeks of start of study drug; * have not recovered from the side effects of any major surgery (defined as requiring general anesthesia but excluding a procedure for insertion of central venous access), or * may require major surgery during the course of the study. * other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin. * patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: * symptomatic congestive heart failure of new york heart association class iii or iv. * unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease. * severely impaired lung function. * uncontrolled diabetes as defined by fasting serum glucose greater than 1.5 upper limit of normal. * active (acute or chronic) or uncontrolled severe infections. * liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis. * other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper gi tract ulceration). * a known history of hiv seropositivity or known immunodeficiency. * women who are pregnant or breast feeding. * patients who have received prior treatment with an inhibitor of mammalian target of rapamycin. * history of noncompliance to medical regimens. * patients unwilling to or unable to comply with the protocol or who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.