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

NCT ID: NCT00352599

Last Updated: 2016-11-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2014-03-31

Brief Summary

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.

Conditions

Neurofibromatosis 1

Keywords

Neurofibromatosis Type 1; NF1; Lovastatin; statin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Lovastatin

Lovastatin

Group Type: ACTIVE_COMPARATOR

Lovastatin

Intervention Type: DRUG

Lovastatin

Intervention Type: DRUG

Lovastatin capsules daily for 14 weeks (titrated up from 10 mg to 40 mg)

Placebo pill

Placebo pill

Group Type: PLACEBO_COMPARATOR

placebo pill

Intervention Type: DRUG

Interventions

Lovastatin

Intervention Type: DRUG

Lovastatin

Lovastatin capsules daily for 14 weeks (titrated up from 10 mg to 40 mg)

Intervention Type: DRUG

placebo pill

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carrie E Bearden, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

Semel Institute for Neuroscience and Human Behavior

Los Angeles, California, United States

Countries

United States

References

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. doi: 10.1016/j.cub.2005.09.043.

Reference Type: BACKGROUND

PMID: 16271875 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20624961 (View on PubMed)

Other Identifiers

05-08-069-01

Identifier Type: -

Identifier Source: org_study_id