Trial to Evaluate the Safety of Lovastatin in Individuals With Neurofibromatosis Type I (NF1)
Information source: University of California, Los Angeles
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Neurofibromatosis 1
Intervention: Lovastatin (Drug); Lovastatin (Drug); placebo pill (Drug)
Phase: Phase 1
Sponsored by: University of California, Los Angeles
Official(s) and/or principal investigator(s):
Carrie E Bearden, PhD, Principal Investigator, Affiliation: University of California, Los Angeles
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.
Official title: Trial to Evaluate the Safety of Lovastatin in Individuals With Neurofibromatosis Type I (NF1)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Non-verbal learning /working memory
tolerability of medication
Minimum age: 10 Years.
Maximum age: 50 Years.
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
1. comorbid neurological conditions
2. significant drug or alcohol abuse
3. non-fluency in English
Locations and Contacts
Semel Institute for Neuroscience and Human Behavior, Los Angeles, California 90095, United States
Li W, Cui Y, Kushner SA, Brown RA, Jentsch JD, Frankland PW, Cannon TD, Silva AJ. The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1. Curr Biol. 2005 Nov 8;15(21):1961-7.
Shilyansky C, Karlsgodt KH, Cummings DM, Sidiropoulou K, Hardt M, James AS, Ehninger D, Bearden CE, Poirazi P, Jentsch JD, Cannon TD, Levine MS, Silva AJ. Neurofibromin regulates corticostriatal inhibitory networks during working memory performance. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13141-6. doi: 10.1073/pnas.1004829107. Epub 2010 Jul 12.
Starting date: September 2009
Last updated: July 14, 2015