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 |
| Secondary identifying numbers | NTR542 |
- 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
Scientific
Erasmus Medical Center
Department of Neurosciences (Ee 12.28)
P.O. Box 1738
Rotterdam
3000 DR
Netherlands
| Phone | +31 (0)10 4087337 |
|---|---|
| l.krab@erasmusmc.nl |
Study information
| Study design | Randomised, double-blind placebo-controlled study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Simvastatin |
| Primary outcome measure | 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 |
| Secondary outcome measures | 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 |
| Overall study start date | 20/01/2006 |
| Completion date | 01/03/2007 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 8 Years |
| Upper age limit | 16 Years |
| Sex | Both |
| Target number of participants | 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
3000 DR
Netherlands
Sponsor information
Erasmus Medical Center (The Netherlands)
Hospital/treatment centre
Hospital/treatment centre
Department of Neurosciences
P.O. Box 1738
Rotterdam
3000 DR
Netherlands
| Website | http://www.erasmusmc.nl/content/englishindex.htm |
|---|---|
"ROR" |
https://ror.org/018906e22 |
Funders
Funder type
Hospital/treatment centre
Sophia Children's Hospital Fund (The Netherlands)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | 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 |
