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

This study has been completed.
Information provided by (Responsible Party):
Carrie Bearden, University of California, Los Angeles Identifier:
First received: July 13, 2006
Last updated: July 14, 2015
Last verified: July 2015

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.

Condition Intervention Phase
Neurofibromatosis 1
Drug: Lovastatin
Drug: placebo pill
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Trial to Evaluate the Safety of Lovastatin in Individuals With Neurofibromatosis Type I (NF1)

Resource links provided by NLM:

Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Non-verbal learning /working memory [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • attention [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
  • tolerability of medication [ Time Frame: 14 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: September 2009
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lovastatin
Drug: Lovastatin Drug: Lovastatin
Lovastatin capsules daily for 14 weeks (titrated up from 10 mg to 40 mg)
Placebo Comparator: Placebo pill
Placebo pill
Drug: placebo pill


Ages Eligible for Study:   10 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00352599

United States, California
Semel Institute for Neuroscience and Human Behavior
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
Principal Investigator: Carrie E Bearden, PhD University of California, Los Angeles
  More Information

Responsible Party: Carrie Bearden, Principal Investigator, University of California, Los Angeles Identifier: NCT00352599     History of Changes
Other Study ID Numbers: 05-08-069-01 
Study First Received: July 13, 2006
Last Updated: July 14, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Los Angeles:
Neurofibromatosis Type 1

Additional relevant MeSH terms:
Neurofibromatosis 1
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplastic Syndromes, Hereditary
Nerve Sheath Neoplasms
Nervous System Diseases
Nervous System Neoplasms
Neurocutaneous Syndromes
Neurodegenerative Diseases
Neuromuscular Diseases
Peripheral Nervous System Diseases
Peripheral Nervous System Neoplasms
L 647318
Anticholesteremic Agents
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action processed this record on May 26, 2016