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

NCT00352599 | Completed Phase 1 DMC

• 1 other identifier: 05-08-069-01
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Non-verbal learning /working memory

  14 weeks

Secondary Outcomes (2)

• attention

  14 weeks

• tolerability of medication

  14 weeks

Study Arms (2)

Lovastatin

ACTIVE COMPARATOR

Lovastatin

Drug: Lovastatin

Placebo pill

PLACEBO COMPARATOR

Placebo pill

Drug: placebo pill

Interventions

Lovastatin DRUG

Lovastatin

placebo pill DRUG

Placebo pill

Eligibility Criteria

• Age: 10 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• a diagnosis of NF1 by NIH criteria
• between 10 and 50 years of age
• no evidence of a comorbid neurological disorder (e.g., epilepsy, encephalitis)
• not currently taking a statin medication
• 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)
• 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.
• not mentally retardation (i.e., IQ greater than 70)
• no evidence of significant and habitual alcohol or drug abuse or dependence
• sufficient acculturation and fluency in the English language to avoid invalidating research measures of thought, language, and speech disorder, and verbal abilities.
• lives in Southern California area (or can arrange \~5 visits to Los Angeles over 14 weeks)

You may not qualify if:

• comorbid neurological conditions
• significant drug or alcohol abuse
• non-fluency in English

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

Semel Institute for Neuroscience and Human Behavior

Los Angeles, California, 90095, United States

Location

Related Publications (2)

• 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.

  PMID: 16271875 BACKGROUND

• 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.

  PMID: 20624961 BACKGROUND

MeSH Terms

Conditions

Neurofibromatosis 1

Interventions

Lovastatin

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Carrie E Bearden, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2006
• First Posted: July 14, 2006
• Study Start: September 1, 2009
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: November 22, 2016

Record last verified: 2016-11

Locations

US (1)