Posted May 10, 2017

Neurofibromatosis Clinical Trials Consortium
Jonathan Payne, DPsych, Belinda Barton, PhD, and Kathryn North, MD, the first and corresponding authors on the publication describing this study

In Fiscal Year 2005 (FY05), the Neurofibromatosis Research Program (NFRP) responded to concerns in the NF field about barriers to development of treatments for NF patients by offering awards for the development of a Clinical Trials Consortium. In the years since, the Neurofibromatosis Clinical Trials Consortium (NFCTC) has grown, and its members have participated together in the design and execution of Phase I and II evaluations of therapeutic agents for the management or treatment of NF1 and NF2. The NFCTC is composed of thirteen clinical sites, five collaborating sites, and an Operations Center at the University of Alabama at Birmingham, under the direction of Dr. Bruce Korf. Since the development awards offered in FY05, the NFCTC has been supported by additional awards from the NFRP in FY06, FY11, and FY16.

In a recently published study, members of the NFCTC performed a randomized placebo-controlled trial of lovastatin in children with neurofibromatosis type 1 (NF1). NF1 is caused by mutations in the NF1 gene, which encodes neurofibromin, a protein that turns off Ras signaling in cells. NF1 has diverse symptoms, but the most commonly observed symptom is cognitive impairment, such as impairment in attention. In animal studies, lovastatin, a statin family drug that reduces Ras activity, showed benefit, leading to studies in humans. Although trials with lovastatin previously showed some beneficial outcomes, trials with a different statin, simvastatin, showed no treatment effect on cognitive impairment.

The investigators in the NFCTC decided to take a closer look at lovastatin for treatment of cognitive impairment and improvement in quality of life for these patients, children aged 8-15 years who had an established learning or attention impairment before starting treatment. The children treated with lovastatin or placebo were evaluated for performance in visuospatial learning and sustained attention, as well as for executive function, overall attention, visuospatial skills, behavior, and quality of life. The investigators found that although the medication was well-tolerated, treatment with lovastatin daily for 16 weeks did not improve cognitive impairments.

The published findings from this study do not support the use of lovastatin to treat cognitive impairments in children with NF1. This study is registered with ClinicalTrials.gov (NCT00853580) and the Australian New Zealand Clinical Trials Registry (ACTRN12607000560493). With the FY16 award, the investigators of the NFCTC will be able to go back to the drawing board, working together towards finding better treatments for all NF patients.

Publication:

Payne JM, Barton B, Ullrich NJ, et al. 2016. Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1. Neurology 87:2575-2584.

Links:

http://www.uab.edu/nfconsortium

Abstracts (Public and Technical): Neurofibromatosis Clinical Consortium Award

Abstracts (Public and Technical): Neurofibromatosis Clinical Consortium Award

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