Condition category
Nervous System Diseases
Date applied
14/02/2006
Date assigned
14/02/2006
Last edited
25/07/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr L.C. Krab

ORCID ID

Contact details

Erasmus Medical Center
Department of Neurosciences (Ee 12.28)
P.O. Box 1738
Rotterdam
3000 DR
Netherlands
+31 (0)10 4087337
l.krab@erasmusmc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

NTR542

Study information

Scientific title

Acronym

NF1 simvastatin trial

Study hypothesis

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

Ethics approval received from the local medical ethics committee.

Study design

Randomised, double-blind placebo-controlled study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

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 names

Simvastatin

Primary outcome measures

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 trial start date

20/01/2006

Overall trial end date

01/03/2007

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

60

Participant 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

Recruitment start date

20/01/2006

Recruitment end date

01/03/2007

Locations

Countries of recruitment

Netherlands

Trial participating centre

Erasmus Medical Center
Rotterdam
3000 DR
Netherlands

Sponsor information

Organisation

Erasmus Medical Center (The Netherlands)

Sponsor details

Department of Neurosciences
P.O. Box 1738
Rotterdam
3000 DR
Netherlands

Sponsor type

Hospital/treatment centre

Website

http://www.erasmusmc.nl/content/englishindex.htm

Funders

Funder type

Hospital/treatment centre

Funder name

Sophia Children's Hospital Fund (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Results in http://www.ncbi.nlm.nih.gov/pubmed/18632543

Publication citations

  1. Results

    Krab LC, de Goede-Bolder A, Aarsen FK, Pluijm SM, Bouman MJ, van der Geest JN, Lequin M, Catsman CE, Arts WF, Kushner SA, Silva AJ, de Zeeuw CI, Moll HA, Elgersma Y, Effect of simvastatin on cognitive functioning in children with neurofibromatosis type 1: a randomized controlled trial., JAMA, 2008, 300, 3, 287-294, doi: 10.1001/jama.300.3.287.

Additional files

Editorial Notes