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

Children with neurofibromatosis type 1 (NF1) frequently demonstrate impairments in attention and visuospatial learning. Despite the significant negative impact of this disorder on cognitive functioning, no studies have examined the effects of interventions on the cognitive functioning of children with NF1. Mice mutated at the NF1 gene provide a useful experimental model to study the biological basis of cognitive deficits in NF1 as they exhibit cognitive impairments that appear to mimic those displayed in children with NF1. Recent evidence has shown that the pharmacological agent lovastatin can reverse attention and learning deficits in NF1 mice. Lovastatin has a 20 year history as in treating hyperlipidemia and Phase I data in children with NF1 suggests that it is safe and tolerable. We intend to conduct a multi-centre, randomised trial examining the efficacy of lovastatin in children with NF1. There will be two treatment groups: one on lovastatin and the other a placebo control. The primary aim will be to establish whether lovastatin significantly improves visuospatial learning and/or sustained attention in children with NF1. Secondary aims include examining the effect of lovastatin on measures of executive function, behaviour and quality of life, as well as further evaluating the toxicity and tolerability of lovastatin in children with NF1.