The effect of simvastatin on the cognitive deficits of children with neurofibromatosis I (NF1): a randomised, double-blind placebo-controlled study

ISRCTN	ISRCTN14965707
DOI	https://doi.org/10.1186/ISRCTN14965707
Protocol serial number	NTR542
Sponsor	Erasmus Medical Center (The Netherlands)
Funder	Sophia Children's Hospital Fund (The Netherlands)

Submission date: 14/02/2006
Registration date: 14/02/2006
Last edited: 25/07/2008

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr L.C. Krab
Scientific

Erasmus Medical Center
Department of Neurosciences (Ee 12.28)
P.O. Box 1738
Rotterdam
3000 DR
Netherlands

Phone	+31 (0)10 4087337
Email	l.krab@erasmusmc.nl

Study information

Primary study design	Interventional
Study design	Randomised, double-blind placebo-controlled study
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	NF1 simvastatin trial
Study objectives	Statin-treatment has been shown to normalise the learning and attention deficits in NF1 +/- mice by decreasing Ras activity. The fact that statins are effective in NF1 mice, combined with their very good safety profile, makes them an ideal candidate drug to treat cognitive impairments associated with NF1 in human patients.
Ethics approval(s)	Ethics approval received from the local medical ethics committee.
Health condition(s) or problem(s) studied	Neurofibromatosis type 1 (NF1)
Intervention	Simvastatin (10 mg/day for month 1, 20 mg/day month 2, 20 mg/day month 3 for children 8-12 years old or 40 mg/day month 3 for children 12-16 years old) or placebo once a day.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Simvastatin
Primary outcome measure(s)	1. Performance on neuropsychological tests on visuospatial memory and attention after 1 and 3 months (Rey Complex Figure test [recall], Bourdon Vos Test) 2. Performance on neurophysiological tests on adaptation of eye movements after 1 and 3 months (saccade-adaptation test, adaptation of eye-hand coordination) 3. Measurement of the size, number, localization and spectra of unidentified bright objects (UBOs), hyperintensities on T2 weighed magnetic resonance imaging (MRI) and 3D CSI 1H magnetic resonance spectroscopy (MRS) after 3 months
Key secondary outcome measure(s)	1. Score on the following neuropsychological tests after 1 and 3 months (after 1 month = under METC review as of 02 May 2006): 1.1. Judgement of line orientation test 1.2. Rey Complex Figure Test (copy) 1.3. Beery VMI Test 2. Score on the following neuropsychological tests after 3 months: 2.1. IQ-test: WISC-RN 2.2. Verbal Fluency Test 2.3. Trailmaking Test A&B 2.4. Wisconsin Card Sorting Test 2.5. Peabody Picture Vocabulary Test 2.6. Boston Naming Test 2.7. 15 Word-Test 2.8. Stroop Color Word Test 3. Identification of facial emotions (ANT). Outcome of the following questionnaires after 3 months: 3.1. Child Behavior Check List (CBCL parents) 3.2. Teacher Report form (TRF) 3.3. Child Behavior Check List (CBCL child) 3.4. Quality of Life Questionnaire CHQ-CF87 Dutch edition (child) (under METC review as of 02 May 2006) 3.5. Quality of Life Questionnaire CHQ-PF50 Dutch edition (parents) (under METC review as of 02 May 2006) 4. Performance on the following neurophysiological tests after 1 and 3 months: 4.1. Basic saccade performance 4.2. Smooth pursuit
Completion date	01/03/2007

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	8 Years
Upper age limit	16 Years
Sex	All
Target sample size at registration	60
Key inclusion criteria	1. Children aged between 8 and 16 years 2. NF1 diagnosis according to the criteria of the National Institutes of Health 3. Visiting the multidisciplinary NF1-outpatient clinic at the Erasmus MC-Sophia Children's Hospital 4. Informed consent
Key exclusion criteria	1. Pathology of the central nervous system (CNS) (hydrocephalus, epilepsy, radiotherapy, neurosurgery etc.) 2. Deafness and/or severely impaired vision 3. Use of anti-epileptics and/or neuroleptics Additional exclusion criteria (under METC review as of 2nd May 2006): 4. Insufficient cognitive abilities to obtain a reliable score on a verbal IQ test (WISC-RN) 5. Contra-indications for simvastatin-treatment 6. Planned hospitalisation within three months after planned date of inclusion
Date of first enrolment	20/01/2006
Date of final enrolment	01/03/2007

Locations

Countries of recruitment

Netherlands

Study participating centre

Erasmus Medical Center

Rotterdam
3000 DR
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	Results	16/07/2008		Yes	No