Professionals (& the protocol)

SimvAstatin in Neurofibromatosis Type 1-Autism (SANTA)

This is a phase II exploratory study of statin treatment in young children aged 5-8 years with NF1 and autism. The purpose of this study is to test acceptability and feasibility of involvement for families and the feasibility of imaging young children with NF1 autism.

The trial is based at the Wellcome Trust Clinical Research Facility in Manchester and is being funding by Central Manchester Foundation Trust.

We are looking to recruit families from across the country and we currently have links with Liverpool, Leeds and Newcastle Genetic departments and have also advertised in the Neurofoundation Website.

Neurofibromatosis Type 1 and Autism Spectrum Disorder

Neurofibromatosis type 1 (NF1) is a common single-gene neurodevelopmental disorder with birth incidence 1 in 2,500 and well-elucidated neuropathology. Noted for somatic manifestations, the main morbidity from NF1 is actually cognitive, social and behavioural difficulties. Clinical studies had suggested attention-deficit-hyperactivity disorder (ADHD) as the main psychopathology along with social difficulties; however our recent studies indicate that 25% of children with NF1 also have autism spectrum disorder. This novel finding represents an important milestone in NF1 research both from a clinical and research perspective.

Research in NF1 knock-out mice has shown us that use of statins can rescue the cognitive and behavioural difficulties associated with NF1. Internationally two trials using statins (one using Simvastatin in the Netherlands and other using Lovastatin in the States) in children with NF1 have been carried out and have reported modest improvement in verbal and non-verbal memory. A functional MRI scan of children with NF1 suggests that statins can normalise resting state functional connectivity in the Default Network region of the brain.

The aim of this proposed study is to ascertain whether Simvastatin can rescue the ASD phenotype in children with NF1 and ASD.

Nature of the trial

The SimvAstatin in Neurofibromatosis Type 1-Autism (SANTA) trial is a single site, triple-blind (clinician/patient/assessor) phase II randomised controlled trial of simvastatin versus placebo. This is a feasibility study which will further inform larger studies. Participants (children aged 5-8 years inclusive) will be identified and recruited from the NF1 clinics in Manchester, Leeds, Liverpool and Newcastle and through advertisements via the Neuro Foundation, the Children with Tumours and NF wellbeing research group newsletters.

Participants will be screened for autism spectrum disorder through the use of postal screening questionnaire. Those meeting the screening criteria will be invited for detailed ASD assessments. Children diagnosed with ASD on these detailed assessments will be invited to participate in the study.

Trial intervention and methodology

The study will be carried out in Wellcome Trust Children's Clinical Research Facility (WTCCRF) at Central Manchester Children's Hospital. Children recruited into the trial will be randomised to receive either Simvastatin or placebo for a period of 12 weeks. Children will be invited to WTCCRF at 0, 4 and 12 weeks. During these visits we will carry out blood tests to monitor for adverse effects of medication and administer parental questionnaires to measure their child's behavioural symptoms. At week 0 and week 12, we will also carry out an MRI scan to look at signals of intervention effects on imaging parameters. The trial intervention will end at 12 weeks. The participants will be followed up via a telephone call 4 weeks after the end of the trial to monitor further progress, acceptability and any delayed adverse effects.

Inclusion criteria

Children between 5-8yrs meeting diagnostic criteria for:

• Neurofibromatosis Type 1(National Institute of Health criteria
• Informed consent

Exclusion criteria

• Patients in active treatment for NF1 complication (e.g. chemotherapy for optic gliomas, Ilizarov frame for pseudarthrosis)
• Parents of patients with insufficient English to complete the ASD screening assessments
• Patients who are a part of any other clinical trial
• Patients taking psychotropic medication other than methylphenidate and/or dextroamphetamines

Title: Phase II triple blind placebo controlled RCT of simvastatin treatment for autism in young children with Neurofibromatosis Type 1

• Protocol (pdf, 5MB)

Referral procedure

You are welcome to ring anyone on the research team to discuss a referral or seek further information about the study. If you think a child meets the above mentioned inclusion criteria, please:

• Provide the families with the Information sheet (pdf, 742KB)
• Contact the research team with the families details who will then send out the screening pack

Contact numbers for research team:

Telephone: +44(0)800 634 0102

Email: santa@manchester.ac.uk