Neurofibromatosis Type 1 MedDRA version: 14.1 Level: LLT Classification code 10029270 Term: Neurofibromatosis, type 1 (von Recklinghausen's disease) System Organ Class: 100000004850
Conditions
Interventions
Trade Name: Simvastatin 20mg/5ml Oral Suspension
Product Name: Simvastatin
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Simvastatin
CAS Number: 79902-63-9
Concentration unit: mg/ml millig
Sponsors
Central Manchester University Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Children between 5-8yrs meeting diagnostic criteria for 1)Neurofibromatosis Type 1(National Institute of Health criteria) 2)Autism Spectrum Disorder (ASD) using Collaborative Programme for Excellence in Autism (CPEA) criteria, based on ADI-R and ADOS-G, age and IQ assessments). 22 3)Patients who are on a stable dose of methylphenidate and/or dexamphetamine for at least three month prior to screening and who will remain on the same dose for the duration of the study. 4)Hepatic function: Patients with normal liver function defined as 60ml/min/1.73m2 calculated by 40 x height (in cm) / plasma creatinine (in micromol/l). 6)Informed consent. Are the trial subjects under 18? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1)Severe learning disability defined as verbal IQ<50 as measured by the WASI. 2)Patients in active treatment for NF1 complication (e.g. chemotherapy for optic gliomas, Ilizarov frame for pseudarthrosis). 3)Individuals with abnormal liver function or renal function at baseline as defined in the inclusion criteria. 4)Parents of patients with insufficient English to complete the ASD screening assessments. 5)Patients taking psychotropic medication other than methylphenidate and/or dextroamphetamines. These patients are eligible if, as clinically indicated, they discontinue medication for at least 30 days prior to screening and remain off these medications for the duration of the study. 6)Patients who have received any investigational drug within 4 months of screening. 7)Patients who have recently taken simvastatin or any other statins. These participants will be eligible after a washout period of at least three months. 8)Patients with a clinically significant unrelated illness, which in the judgment of the principal or associate investigator, would compromise the participant’s ability to tolerate the medication or interfere with ability to participate in the required testing. 9)Low cholesterol (defined as total cholesterol < 90mg/dl). 10)Patients with planned surgery within 16 weeks of potential enrolment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The overall research aim is to determine whether treatment with statins improves the ASD phenotype in children with NF1 autism. This aim of this study is to test: -Acceptability and feasibility of involvement for families of children with NF1 ASD -The feasibility and acceptability of the assessment protocol -Treatment effects on intermediate and endpoint behavioural phenotype measures and imaging parameters The hypothesis is that treatment with statins in young children with NF1 autism will be: -Feasible, safe and acceptable to families -Associated with signals of change in brain imaging parameters -Associated with signals of change in autism and other behavioural symptoms ;Primary end point(s): The endpoint outcome measures for the study are: -ASD symptoms as assessed by the behavioural phenotype measures -Effect of 12 weeks of Simvastatin treatment on multi-parametric imaging findings including anatomical, physiological, spectroscopic and resting state functional connectivity in the default network as assessed at 3T MRI - Telephone interviews with parents on experience of trial, intervention, assessments including imaging procedures. ;Secondary Objective: None;Timepoint(s) of evaluation of this end point: Timepoints of evaluation for the endpoints are: - ASD behavioural phenotype measures at 0,4 and 12 weeks - Imaging measures at 0 and 12 weeks - Telephone interviews with parents at 16 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
United Kingdom
Contacts
Public ContactResearch Secretary
Central Manchester University Hospitals NHS Foundation Trust
Outcome results
None listed