A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1
Condition: Neurofibromatosis Type 1
MeSH terms: Neurofibromatoses; Neurofibromatosis 1; Neurofibroma
Study type: Interventional
Phase: Phase 2

Summary: 
      The specific aim of this study is to determine whether Lovastatin ™ significantly improves
      visual spatial learning and/or sustained attention in children with NF1.

      Secondary Aims:

      To evaluate the effect of Lovastatin ™ on measures of executive function, behavior and
      quality of life in children with NF1 and cognitive deficits.

      To further evaluate the toxicity and tolerability of Lovastatin ™ in children with NF1 and
      cognitive deficits.

      Hypotheses

      It is hypothesized that Lovastatin ™ will improve the visual spatial memory and/or attention
      deficits in children with NF1. This is based on studies demonstrating that Lovastatin ™ has
      significantly improved impairments in visual spatial memory and attention in the NF1 murine
      model.

      It is further expected that Lovastatin ™ will be safe and well tolerated over a 16-week
      period.
    

Detailed description: 
      Study Design

      This is a prospective multi-centre randomized, placebo-controlled Phase II study to determine
      the efficacy of Lovastatin ™ on visual spatial learning and/or attention abilities of
      children with NF1 aged between 8 and less than 16 years. In addition, the effect of
      Lovastatin ™ on secondary measures of executive function, visual spatial skills, behavior and
      quality of life will be assessed. Participants will be randomized to 16-weeks of treatment
      with Lovastatin ™ or a matched placebo. It is plausible and ethical to employ a placebo group
      as no standard therapy with established efficacy is being withheld. There is no cross-over in
      this study due to a lack of data concerning the length of possible washout effects. The
      Lovastatin ™ dose will begin at 20 mg once daily/continuous dosing and escalate over a
      two-week period to 40 mg once daily/continuous dosing and continue at this dose for 14 weeks.
      Participants will be carefully monitored for side effects. The safety of Lovastatin ™ will be
      evaluated using laboratory tests, clinical signs and adverse effects, which will be monitored
      at regular intervals over the 16-week period. Primary and secondary outcome measures will be
      administered at baseline, 16 weeks post-treatment and at follow-up, 8 weeks after cessation
      of treatment to determine any carry-over effects. The safety of Lovastatin ™ will also be
      evaluated, with regular monitoring of side-effects during the trial.

      Study Population

      This is a Phase II study involving children with NF1 (aged between 8 years to 15 years 11
      months old at time of enrollment) with evidence of cognitive impairment, defined as having a
      score of at least one standard deviation or more below the population mean on a measure of
      visual spatial learning and/or attention.

      A total of 142 participants with NF1 aged between 8 years and 15 years 11 months will be
      enrolled in the study. The age limits were selected on the basis that Lovastatin ™ has been
      shown to be safe in children aged between 8 and 17 years old. In addition, one of the primary
      outcome measures (attention) only has normative data for up to 15 years 11 months. Therefore,
      the maximum age limit for participants at time of enrolment is 15 years 11 months so that
      normative data can be used to determine whether participants are impaired. The pediatric NF1
      population is an ideal group in which to study the cognitive effects of Lovastatin ™ because
      it represents an opportunity for early pharmacological intervention of cognitive deficits.
    

Intervention name(s): Lovastatin ™; placebo
Intervention type(s): Drug; Device
Intervention description(s): Lovastatin starting at 20mg for 2 weeks, increasing to 40mg for 14 weeks. Total duration of trial is 16 weeks.; Starting at 20mg for 2 weeks, then increasing to 40mg for 14 additional weeks for a total duration of treatment of 16 weeks.
Intervention MeSH terms: Lovastatin; L 647318; Dihydromevinolin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Neurofibromatosis Type 1, Neurocognitive, Phase II