Clinical Trial: A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1

Brief 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 Summary:

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 an
Sponsor: University of Alabama at Birmingham

Current Primary Outcome:

  • Visual Spatial Learning: Paired Associate Learning (Cambridge Neuropsychological Test Automated [ Time Frame: 16 weeks ]
  • Attention: *Score! (Test of Everyday Attention for Children, TEA-Ch) [ Time Frame: 16 weeks ]


Original Primary Outcome: Visual Spatial Learning and Memory; Attention: *Score!; and TEA-Ch. [ Time Frame: 16 weeks ]

Current Secondary Outcome:

  • Conners' Continuous Performance Task - II (CPT-II) [ Time Frame: 16 weeks ]
  • Sky Search (TEA-Ch) [ Time Frame: 16 weeks ]
  • Sky Search DT (TEA-Ch) [ Time Frame: 16 weeks ]
  • Creature Counting (TEA-Ch) [ Time Frame: 16 weeks ]
  • Spatial Working Memory (CANTAB) [ Time Frame: 16 weeks ]
  • Stockings of Cambridge (CANTAB) [ Time Frame: 16 weeks ]
  • Controlled Oral Word Association Test (COWAT) [ Time Frame: 16 weeks ]
  • Judgment of Line Orientation [ Time Frame: 16 weeks ]
  • Object Assembly (Wechsler Scale for Intelligence - Third edition) [ Time Frame: 16 weeks ]
  • Conners ADHD/DSM-IV Scales (CADS: parent report): ADHD Inattentive Symptoms and Hyperactive/Impulsive Symptoms [ Time Frame: 16 weeks ]
  • Behavior Rating Inventory of Executive Function (BRIEF, parent report): Global Executive Composite [ Time Frame: 16 weeks ]
  • Pediatric Quality of Life (PedsQL 4.0 Generic Cole Scales, parent and child self-report): Psychosocial Health Summary Score [ Time Frame: 16 weeks ]


Original Secondary Outcome: Conners' Continuous Performance Task - II (CPT-II: Conners, 2000) [ Time Frame: 16 weeks ]

Information By: University of Alabama at Birmingham

Dates:
Date Received: February 23, 2009
Date Started: July 2009
Date Completion: December 2017
Last Updated: May 3, 2017
Last Verified: May 2017