No registrations found.
ID
Source
Brief title
Health condition
Neurofibromatosis 1; Neurofibromatose type 1; NF1
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Cognitive Function: WISC III-R;
2. Behavioral Problems on the Child Behavioral Checklist (CBCL, parents): internalizing behavioral problems, attention problems.
Secondary outcome
1. School performance: Teacher ratings form the Teacher Report Form;
2. Quality of Life: CHQPF50 Child Quality of Life Questionnaire;
3. Behavior (other): internalizing problems rated by children on the Youth Self Report;
4. Cognitive Function (other): Non-verbal Long term Memory by the Rey Complex Figure test – delayed recall;
5. Attention (other): Stroop color word test;
6. Fine motor coordination: Grooved Pegboard test.
Background summary
Children with Neurofibromatosis type 1 (NF1, prevalence 1:3000) commonly display cognitive deficits that have a large impact on behaviour, school performance and quality of life. Mouse model studies showed that the learning deficits are due to increased RAS signalling. This increased signalling, as well as the synaptic plasticity deficits and learning deficits of these mice can be rescued by statin-mediated inhibition of HMG-CoA reductase. Statins are the most commonly prescribed drugs worldwide, and have a very favourable safety profile. Hence, this provides us with a unique opportunity to assess the effect of a targeted treatment on cognitive performance and behaviour in patients. We have previously conducted a 12-week pilot study in children with NF1 (ISRCTN14965707). Although we did not find a significant improvement compared to placebo in the primary outcome measures, we did obtain preliminary data that statins improved some measures. We consider it certainly possible that there is indeed a significant therapeutic benefit, but that the overall treatment was too short to detect this in the pilot trial. In addition, the clinical outcome measures may have been unable to reflect a potential benefit in daily life functioning. Furthermore, we found indications that ADHD-medication may mask the beneficial effect of Simvastatin on attention, thus patients that are treated with ADHD-medication will be excluded from this trial. This trial will aim to clarify the effect of long-term Simvastatin treatment on cognition and daily life functioning in children with NF1.
Study objective
Simvastatin can have a positive effect on cognitive function and daily life functioning in children with Neurofibromatosis 1.
Study design
Baseline (T=0 months) and end of treatment (T=12 months).
Intervention
Participants are treated for 12 months with Simvastatin (10 mg/d in month 1, 20 mg/d in month 2, and then 20 mg/d for participants 8-12 years old or 40 mg/d for participants 13-16 years old) or equivalent placebo once a day in the morning).
M.H.T. Vaart, van der
Rotterdam 3000 CA
The Netherlands
+31 (0)10 7043751
m.vandervaart@erasmusmc.nl
M.H.T. Vaart, van der
Rotterdam 3000 CA
The Netherlands
+31 (0)10 7043751
m.vandervaart@erasmusmc.nl
Inclusion criteria
1. Age 8 to 16 years;
2. NF1 diagnosis with genetic confirmation;
3. Oral and written informed consent from parents and participants aged older than 12 years.
Exclusion criteria
1. Segmental NF1;
2. Pathology of the CNS (other than asymptomatic gliomas);
3. Deafness;
4. Severely impaired vision;
5. Use of ADHD-medication;
6. Use of anti-epileptic drugs;
7. Use of anti-psychotic medication;
8. Use of Simvastatin;
9. Insufficient comprehension or production of the Dutch language;
10. An IQ below 48.
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL2033 |
| NTR-old | NTR2150 |
| CCMO | NL27196.000.09 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |