The effect of long-term Simvastatin treatment on cognitive function and daily life in children with Neurofibromatosis 1: a one year randomized controlled trial.

Children with Neurofibromatosis type 1 (NF1, prevalence 1:3000) commonly display cognitive deficits that have a large impact on behaviour, school performance and quality of life. Mouse model studies showed that the learning deficits are due to increased RAS signalling. This increased signalling, as well as the synaptic plasticity deficits and learning deficits of these mice can be rescued by statin-mediated inhibition of HMG-CoA reductase. Statins are the most commonly prescribed drugs worldwide, and have a very favourable safety profile. Hence, this provides us with a unique opportunity to assess the effect of a targeted treatment on cognitive performance and behaviour in patients. We have previously conducted a 12-week pilot study in children with NF1 (ISRCTN14965707). Although we did not find a significant improvement compared to placebo in the primary outcome measures, we did obtain preliminary data that statins improved some measures. We consider it certainly possible that there is indeed a significant therapeutic benefit, but that the overall treatment was too short to detect this in the pilot trial. In addition, the clinical outcome measures may have been unable to reflect a potential benefit in daily life functioning. Furthermore, we found indications that ADHD-medication may mask the beneficial effect of Simvastatin on attention, thus patients that are treated with ADHD-medication will be excluded from this trial. This trial will aim to clarify the effect of long-term Simvastatin treatment on cognition and daily life functioning in children with NF1.

Simvastatin can have a positive effect on cognitive function and daily life functioning in children with Neurofibromatosis 1.

Baseline (T=0 months) and end of treatment (T=12 months).

Participants are treated for 12 months with Simvastatin (10 mg/d in month 1, 20 mg/d in month 2, and then 20 mg/d for participants 8-12 years old or 40 mg/d for participants 13-16 years old) or equivalent placebo once a day in the morning).