Trial Summary & protocol

Title & protocol

Phase 2 triple blind placebo controlled RCT of simvastatin treatment for autism in young children with Neurofibromatosis Type 1.  Here is the PROTOCOL.


Single site, 2 parallel groups, triple-blind (clinician/patient/assessor) phase II randomised trial of simvastatin (n=15) versus placebo (n=15) in a dose titration design. 


The research aims are to test:

  • The feasibility, safety and acceptability of treatment with simvastatin to children with NF1 and Autism Spectrum Disorder.
  • The feasibility and acceptability of the assessment protocol.
  • Treatment effects on intermediate and endpoint behavioural phenotype measures and imaging parameters.


We will measure functional imaging parameters; blinded parent and clinician rated autism and behavioural symptoms; patient acceptability and adverse effects at baseline, 12 week primary endpoint and 16 week post-treatment. Intermediate assessment at 4 weeks will be made of physiological and biochemical parameters for adverse effects.


This is a phase II feasibility study of children with NF1 autism. A total of 30 participants (children between 5-8 years inclusive) will be identified and recruited from the NF1 clinics in Manchester, Liverpool, Leeds and Newcastle and through advertisements via the NeuroFoundation and NF wellbeing research group newsletters.

Trial Treatment and methods

After baseline monitoring, children will be randomised to receive either placebo or simvastatin at 0.5 mg/kg/day in a single daily dose for 4 weeks, and their status reviewed. Those showing no significant adverse effects (e.g. elevation of Liver Function Tests or Creatine Kinase) will be escalated to a dose of 1 mg/kg/day to a maximum of 30 mg/day in a single daily dose for a further 8 weeks.  The trial intervention will end at 12 weeks. The participants will be followed up via a telephone call at 16 weeks (4 weeks after the end of the trial intervention) to monitor further progress, acceptability and any delayed adverse effects.

Blood tests for monitoring adverse events will include lipids, liver function tests (LFT), Urea & Electrolytes (U&E) and Creatine Kinase (CK).

The behavioural phenotype measures will include Aberrant Behaviour Checklist-Community (ABC-C); Patient defined target symptoms and Clinician Global Impression of Improvement (CGI) and Conners Parent Rating Scale – Research (CPRS-R).

Brain scans including Functional MRI scan and multi-voxel proton magnetic resonance spectroscopy at week 0 and week 12 for the child.

Post-intervention evaluation at 16 weeks will consist of telephone follow-up screening for adverse events and qualitative interviews with parents on experience of trial, intervention, assessments including imaging procedures.

Trial duration per participant

The trial duration per participant will be 16 weeks.

Estimated total trial duration

The total trial duration will be 18 months.

Total number of participants planned

30 participants will be included in this study randomised to either treatment or placebo arm.

Additional trials/ Sub-trials

Blood samples collected, as part of this study will be used to carry out the following sub-trials:

  • MAPK level as a peripheral biomarker for cognitive deficits of NF1: The aim of this exploratory study is to ascertain pre and post MAPK levels as a potential biomarker for simvastatin treatment effects
  • NF1 mutational analysis and evaluation of genotype-phenotype correlation: The aim of this study is to look at the mutations of the NF1 gene and correlate that with the clinical ASD phenotype.