Official Title: “Trial to Evaluate the Safety of Lovastatin in Adults With Neurofibromatosis Type I (NF1)”

Neurofibromatosis type I (NF1) is a genetic disorder that affects approximately 1 in 3500 individuals. Half of people with NF1 inherit the condition from a parent, and half have a new occurrence of the condition. The manifestation of NF1 is highly variable and multiple organ systems are typically affected. Some of the more common symptoms include benign neurofibromas, café au lait spots, Lisch nodules (tan spots on the iris of the eye). Some individuals with NF1 also exhibit more severe associated conditions, such as optic pathway tumors (gliomas) or bones bending or curving. Neurocognitive deficits and specific learning disabilities occur in approximately 30 to 50% of individuals with NF1 and are regarded by some observers and sufferers to be among the most troubling features of a disease. The most commonly reported findings are deficits in visuoperceptual ability, motor coordination, expressive and receptive language, and executive functioning, which requires intact short-term memory and attention. Patients with NF1 also show a slight depression in mean IQ scores compared to healthy adults without the disorder. While cognitive deficits are now a widely-recognized feature of NF1, the precise cause of these deficits still remain to be determined. Dr. Alcino Silva, a co-investigator on the proposed project, has developed an animal model of NF1 in which mice have a specific mutation of the NF1 gene. These mice are physically normal but show specific learning impairments. Dr. Silva's lab found that treatment with a medication called lovastatin, a drug typically used for high cholesterol, reversed some of the spatial deficits seen in these animals. Lovastatin is a medication commonly used to treat high cholesterol and has been proven to be relatively safe and tolerable in humans; however, there is no information about its safety specifically among people with NF1. Our goal is to first establish the safety of this medication among individuals with NF1 and then, if safe, move on to conducting a study to evaluate whether this medication might be helpful in treatment of cognitive problems in individuals diagnosed with NF1. We are conducting a randomized, double-blinded, placebo-controlled, safety study of lovastatin in patients with NF1. Participants will be randomly assigned to lovastatin or placebo and treated for approximately 8 weeks with baseline and follow-up assessments to evaluate safety and any effects on neurocognitive test performance.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Intervention(s) in this Clinical Trial

• Drug: Lovastatin

Inclusion Criteria:

• 1. a diagnosis of NF1 by NIH criteria
• 2. between 18 and 45 years of age
• 3. no evidence of a comorbid neurological disorder (e.g., epilepsy, encephalitis)
• 4. not currently taking a statin medication
• 5. not suffering from hypercholesterolemia based on self-report, collateral information from physician, or initial medical workup using National Cholesterol Education Program (NCEP, JAMA 2001), guidelines accepted by the American College of Cardiology (ACC) and the American Heart Association (AHA)
• 6. does not have any of the aforementioned conditions that contraindicates use of statin medications (such as pregnancy, lactation, liver disease, or use of other medication not recommended for use in conjunction with lovastatin). A negative pregnancy test will be required if the patient is a female in reproductive years.
• 7. not mentally retardation (i.e., IQ greater than 70)
• 8. no evidence of significant and habitual alcohol or drug abuse or dependence
• 9. sufficient acculturation and fluency in the English language to avoid invalidating research measures of thought, language, and speech disorder, and verbal abilities.

Exclusion Criteria:

• 1. comorbid neurological conditions
• 2. significant drug or alcohol abuse
• 3. non-fluency in English

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of California, Los Angeles

Overall Clinical Trial Officials and Contacts

Tyrone Cannon, PhD Principal Investigator University of California, Los Angeles  

Overall Contact: Molly E Hardt (310) 794-9730 hardt@lifesci.ucla.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00352599

Study ID Number: 05-08-069-01

ClinicalTrials.gov Identifier: NCT00352599

Health Authority: United States: Institutional Review Board