None listed
Conditions
Brief summary
Children with neurofibromatosis type 1 (NF1) frequently demonstrate impairments in attention and visuospatial learning. Despite the significant negative impact of this disorder on cognitive functioning, no studies have examined the effects of interventions on the cognitive functioning of children with NF1. Mice mutated at the NF1 gene provide a useful experimental model to study the biological basis of cognitive deficits in NF1 as they exhibit cognitive impairments that appear to mimic those displayed in children with NF1. Recent evidence has shown that the pharmacological agent lovastatin can reverse attention and learning deficits in NF1 mice. Lovastatin has a 20 year history as in treating hyperlipidemia and Phase I data in children with NF1 suggests that it is safe and tolerable. We intend to conduct a multi-centre, randomised trial examining the efficacy of lovastatin in children with NF1. There will be two treatment groups: one on lovastatin and the other a placebo control. The primary aim will be to establish whether lovastatin significantly improves visuospatial learning and/or sustained attention in children with NF1. Secondary aims include examining the effect of lovastatin on measures of executive function, behaviour and quality of life, as well as further evaluating the toxicity and tolerability of lovastatin in children with NF1.
Interventions
We will evaluate the efficacy of lovastatin, a 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMG-CoA reductase) inhibitor, on visual spatial learning and sustained attention. Children in the treatment condition will initally take a titrated dose of lovastatin (20mg/day) for 2 weeks, followed by 40mg of lovastatin once per day for 14 weeks.
Sponsors
Prof Kathryn North
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
8 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females aged between 8-15 years of age who meet National Institutes of Health (NIH) diagnostic criteria for neurofibromatosis type 1 (NF1). 2. Full scale intellectual quotient (IQ) of 70 or above. 3. Cognitive impairment defined as having a score of at least 1 standard deviation or more below the normative mean on one or more of the primary outcome measures.
Exclusion criteria
1. Full scale IQ score less than 70. 2. Individuals with insufficient English to complete the assessments. 3. Participants taking stimulant medication or Straterra, as it is unclear whether lovastatin and ADHD medication utilise similar biological pathways, possibly leading to an interaction between the two medications 4. Participants on psychotropic or antiepileptic medication 5. Participants with intracranial pathology such as epilepsy, diagnosed head injury, hydrocephalus or progressive intracranial tumors (children with asymptomatic or static lesions will be eligible). 6. Participants who are pregnant or breastfeeding. 7. Participants with a clinically significant unrelated illness, which in the judgement of the principle or associate investigator, would compromise the participant's ability to tolerate the medication or potentially interfere with the participant's ability to participate in the required testing. 8. Children with very low LDL cholesterol levels pre-treatment (1 mmol/L). LDL levels within the normal range are required pre-treatment as lovastatin has been shown to lower levels of LDL cholesterol by approximately 30%.
Outcome results
None listed