A randomised placebo-controlled study of lovastatin in children with neurofibromatosis type 1

INTERVENTION: We will evaluate the efficacy of lovastatin, a 3‐hydroxy‐3‐methylglutaryl‐Coenzyme A reductase (HMG‐CoA reductase) inhibitor, on visual spatial learning and sustained attention. Children in the treatment condition will initally take a titrated dose of lovastatin (20mg/day) for 2 weeks, followed by 40mg of lovastatin once per day for 14 weeks. CONDITION: Neurofibromatosis type 1 Neuropsychological impairment PRIMARY OUTCOME: Sustained attention: Mean score on "Score!" subtest of the Test of Everyday Attention for Children (TEA‐Ch). Visuospatial learning: Mean Total Errors Adjusted score on the "Paired Associate Learning" subtest from the Cambridge Neuropsychological Test Automated Battery (CANTAB). SECONDARY OUTCOME: "Motor Screening" from the CANTAB Attention Score from the "Sky Search" subtest from the TEA‐Ch Conners' Continuous Performance Test ‐ II Dual Task Decrement from the "Sky Search DT" subtest from the TEA‐Ch Judgement of Line Orientation Mean Total Errors from the "Spatial Working Memory" subtest from the CANTAB Problems solved in minimum moves from the "Stockings of Cambridge" subtest from the CANTAB Questionnaires: Conners ADHD/DSM‐IV Scales (CADS; Parent Report); Behavior Rating Inventory of Executive Function (Parent Form), Behavior Assessment System for Children ‐ II (Parent Report & Self Report), The Pediatric Quality of Life Scale (Parent Report & Self Report). The "Stop Signal Task" from the CANTAB Total Correct and Timing Score from the "Creature Counting" subtest from the TEA‐Ch Total words on the "Controlled Oral Word Association Test". INCLUSION CRITERIA: 1. Males or females aged between 8‐15 years of age who meet National Institutes of Health (NIH) diagnostic criteria for neurofibromatosis type 1 (NF1). 2. Full scale intellectual quotient (IQ) of 70 or above. 3. Cognitive impairment defined as having a score of at least 1 standard deviation or more below the normative mean on one or more of the primary outcome measures.