Trial to Evaluate the Safety of Lovastatin in Individuals With Neurofibromatosis Type I (NF1)

Official Title: “Trial to Evaluate the Safety of Lovastatin in Individuals 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 Neurofibromatosis Type 1 (NF1), the precise cause of these deficits still remain to be determined. Dr. Alcino Silva, a co- investigator on this study, 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.

The investigators are now conducting a randomized, double-blinded, placebo- controlled, trial of lovastatin in patients with NF1. Participants will be randomly assigned to lovastatin or placebo and treated for approximately 14 weeks with baseline and follow-up assessments to evaluate safety and any effects on neurocognitive test performance.

Intervention(s) in this Clinical Trial

• Drug: Lovastatin
• Drug: Lovastatin
  • Lovastatin capsules daily for 14 weeks (titrated up from 10 mg to 40 mg)
• Drug: placebo pill

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Lovastatin
• Placebo Comparator: Placebo pill

Primary Measures

• Non-verbal learning
  • Time Frame: 14 weeks
    Safety Issue?: No

Secondary Measures

• attention
  • Time Frame: 14 weeks
    Safety Issue?: No
• tolerability of medication
  • Time Frame: 14 weeks
    Safety Issue?: Yes

Inclusion Criteria:

• 1. a diagnosis of NF1 by NIH criteria
• 2. between 10 and 50 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.
• 10. lives in Southern California area (or can arrange ~5 visits to Los Angeles over 14 weeks)

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: 10 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: University of California, Los Angeles Other

Overall Clinical Trial Officials and Contacts

Carrie E Bearden, PhD Principal Investigator University of California, Los Angeles  

Overall Contact: Jennifer Ho, B.S. (310) 825-3458 jennho@ucla.edu

Information obtained from ClinicalTrials.gov on February 12, 2012

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