A Randomized Placebo-Controlled Study of Lovastatin in Children with Neurofibromatosis Type 1
The study is a prospective, multi-center randomized, placebo-controlled Phase II study of the efficacy of Lovastatin on visual spatial learning and/or attention abilities of children with NF1 aged 8 to less than 16 years with cognitive impairment. Potential participates will undergo inital screening after being consent, including medical history, physical examination, laboratory testing and initial psychological screening (CANTAB paired associate learning, Score! Subtest from the Test of Everyday Attention for Children among others). Patients who are eligilbe for study after initial screening will be randomized to one of two treatment groups, oral Lovastatin or placebo for up to 16 weeks. At the end of the treatment period, all outcome measures will be re-administered. The primary outcome measure is visual spatial learning and attention. Secondary measures include measures of exectuive function, behavior and quality of life.
Males or females aged between 8 years to less than 16 years at time of screening who meet NIH diagnostic criteria for NF1 (Appendix 1); Participants must have a full-scale IQ of 70 or above. In cases where there is a statistically significant difference between verbal IQ and performance IQ (.05 level as determined by Table B3 in the WASI manual), participants will be eligible if at least one of these quotients is 70 or above; Participants must have a cognitive impairment defined as having a score of at least one standard deviation or more below the population mean on one or more of the primary objective outcome measures (i.e., impaired on a measure of visual spatial learning and/or sustained attention); Participants must be medically stable; Participants who are on a stable dose of methylphenidate and/or dextroamphetamines for at least one month prior to screening and who will remain on the same dose for the duration of the study (see Section 4.3 for exclusion criteria regarding other psychotropic medication, i.e. medication capable of affecting the mind, emotions or behavior) Hepatic function: Participants must have adequate liver function defined as at least 3 of the 4 liver function tests to be < 2 x upper limit of normal for age according to institution standards (AST, ALT, Direct bilirubin, Indirect bilirubin [computed from total bilirubin and direct bilirubin]) and no tests should be >5x upper limit of normal for age; Renal function: Participants must have adequate renal function defined as serum creatinine <= 1.5x upper limits of normal for age, and BUN <= 1.5x upper limits of normal for age or a creatinine clearance of greater than 70 ml/m/1.73m2; Hematologic function: Participants must have an absolute neutrophil count of > 1,000, a hemoglobin >=10 gms/dl, and a platelet count > 100,000 on study entry; Participants must sign all required documents, including informed assent and HIPAA documents; Female participants of childbearing age should not be pregnant, must have a negative pregnancy test before initiation of treatment, and take appropriate birth control precautions to participate in this study.