A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1 (STARS)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Children's Hospital Boston
Children's Hospital Philadelphia
Children's Research Institute
Children's Hospital Medical Center, Cincinnati
University of Chicago
University of Utah
Washington University School of Medicine
The Children's Hospital at Westmead
University of Texas Southwestern Medical Center
Information provided by (Responsible Party):
Bruce Korf, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00853580
First received: February 23, 2009
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

The specific aim of this study is to determine whether Lovastatin ™ significantly improves visual spatial learning and/or sustained attention in children with NF1.

Secondary Aims:

To evaluate the effect of Lovastatin ™ on measures of executive function, behavior and quality of life in children with NF1 and cognitive deficits.

To further evaluate the toxicity and tolerability of Lovastatin ™ in children with NF1 and cognitive deficits.

Hypotheses

It is hypothesized that Lovastatin ™ will improve the visual spatial memory and/or attention deficits in children with NF1. This is based on studies demonstrating that Lovastatin ™ has significantly improved impairments in visual spatial memory and attention in the NF1 murine model.

It is further expected that Lovastatin ™ will be safe and well tolerated over a 16-week period.


Condition Intervention Phase
Neurofibromatosis Type 1
Drug: Lovastatin ™
Device: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Visual Spatial Learning and Memory; Attention: *Score!; and TEA-Ch. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Conners' Continuous Performance Task - II (CPT-II: Conners, 2000) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 142
Study Start Date: July 2009
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 2
This is a prospective multi-centre randomized, placebo-controlled Phase II study to determine the efficacy of Lovastatin ™ on visual spatial learning and/or attention abilities of children with NF1 aged between 10 and 16 years. In addition, the effect of Lovastatin ™ on secondary measures of executive function, visual spatial skills, behavior and quality of life will be assessed. Participants will be randomized to 16-weeks of treatment with Lovastatin ™ or a matched placebo.
Device: placebo
Starting at 20mg for 2 weeks, then increasing to 40mg for 14 additional weeks for a total duration of treatment of 16 weeks.
Experimental: 1
This is a prospective multi-centre randomized, placebo-controlled Phase II study to determine the efficacy of Lovastatin ™ on visual spatial learning and/or attention abilities of children with NF1 aged between 10 and 16 years. In addition, the effect of Lovastatin ™ on secondary measures of executive function, visual spatial skills, behavior and quality of life will be assessed. Participants will be randomized to 16-weeks of treatment with Lovastatin ™ or a matched placebo.
Drug: Lovastatin ™
Lovastatin starting at 20mg for 2 weeks, increasing to 40mg for 14 weeks. Total duration of trial is 16 weeks.

Detailed Description:

Study Design

This is a prospective multi-centre randomized, placebo-controlled Phase II study to determine the efficacy of Lovastatin ™ on visual spatial learning and/or attention abilities of children with NF1 aged between 10 and 16 years. In addition, the effect of Lovastatin ™ on secondary measures of executive function, visual spatial skills, behavior and quality of life will be assessed. Participants will be randomized to 16-weeks of treatment with Lovastatin ™ or a matched placebo. It is plausible and ethical to employ a placebo group as no standard therapy with established efficacy is being withheld. There is no cross-over in this study due to a lack of data concerning the length of possible washout effects. The Lovastatin ™ dose will begin at 20 mg once daily/continuous dosing and escalate over a two-week period to 40 mg once daily/continuous dosing and continue at this dose for 14 weeks. Participants will be carefully monitored for side effects. The safety of Lovastatin ™ will be evaluated using laboratory tests, clinical signs and adverse effects, which will be monitored at regular intervals over the 16-week period. Primary and secondary outcome measures will be administered at baseline, 16 weeks post-treatment and at follow-up, 8 weeks after cessation of treatment to determine any carry-over effects. The safety of Lovastatin ™ will also be evaluated, with regular monitoring of side-effects during the trial.

Study Population

This is a Phase II study involving children with NF1 (aged between 10 years to 15 years 11 months old at time of enrollment) with evidence of cognitive impairment, defined as having a score of at least one standard deviation or more below the population mean on a measure of visual spatial learning and/or attention.

A total of 142 participants with NF1 aged between 10 years and 15 years 11 months will be enrolled in the study. The age limits were selected on the basis that Lovastatin ™ has been shown to be safe in children aged between 10 and 17 years old. In addition, one of the primary outcome measures (attention) only has normative data for up to 15 years 11 months. Therefore, the maximum age limit for participants at time of enrolment is 15 years 11 months so that normative data can be used to determine whether participants are impaired. The pediatric NF1 population is an ideal group in which to study the cognitive effects of Lovastatin ™ because it represents an opportunity for early pharmacological intervention of cognitive deficits.

  Eligibility

Ages Eligible for Study:   10 Years to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Males or females aged between 10 years and 15 years 11 months at time of enrollment who meet NIH diagnostic criteria for NF1 (Appendix 1)
  • Participants must have a full-scale IQ of 70 or above
  • Participants must have a cognitive impairment defined as having a score of at least one standard deviation or more below the population mean on one or more of the primary objective outcome measures (i.e., impaired on a measure of visual spatial learning and/or sustained attention)
  • Participants must be medically stable
  • Participants with NF1 and a diagnosis of ADHD who are not taking stimulant or non-stimulant medication
  • Hepatic function:
  • Participants must have a bilirubin within normal limits and AST and ALT ± 2 times the upper limit of normal as determined by the standards at their institution
  • Renal function:
  • Participants must have an age-adjusted normal serum creatinine or a creatinine clearance of greater than 70 ml/m/1.73m2
  • Hematologic function:
  • Participants must have an absolute neutrophil count of greater than 1,500, a hemoglobin of greater than 9 gms/dl, and a platelet count of greater than 100,000 on study entry
  • Participants must sign all required documents, including informed assent and HIPAA documents
  • Female participants of childbearing age should not be pregnant, must have a negative pregnancy test before initiation of treatment, and take appropriate birth control precautions to participate in this study.

Exclusion Criteria:

  • Full-scale IQ less than 70;Individuals that are not cognitively impaired on at least one of the primary objective outcome measures
  • Individuals with insufficient English to complete the assessments
  • Participants taking stimulant medication or stratera will be excluded because it is unclear whether Lovastatin ™ and ADHD medication utilize similar biological pathways, possibly leading to an interaction between the two medications
  • Participants on psychotropic, behavioral, or antiepileptic medication
  • Participants with intracranial pathology such as epilepsy, diagnosed head injury, hydrocephalus or progressive intracranial tumors (children with asymptomatic or static lesions will be eligible)
  • Participants who are pregnant or breastfeeding; Participants who have received any investigational drugs of any type within 30 days of initiation of study
  • Participants who participated in a Phase I trial of Lovastatin ™ or who have previously taken Lovastatin ™
  • Participants with significant hepatic, renal or hematologic function as previously defined
  • Participants with a history of neuromuscular disease, excluding hypotonias thought to be associated with NF1
  • Participants with a clinically significant unrelated illness, which in the judgment of the principal or associate investigator, would compromise the participant's ability to tolerate the medication or potentially interfere with the participant's ability to participate in the required testing
  • Low cholesterol (lower limit of a total cholesterol of 100mg/dl (2.56mmol/L)
  • Participants who have taken sirolimus within three months of enrollment. These participants are eligible after a washout period of at least three months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00853580

Locations
United States, Alabama
The University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Massachusetts
Children' Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University - St. Louis
St. Louis, Missouri, United States, 63110
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19096
United States, Texas
Childrens Medical Center - Univ. of Texas SW Medical Center
Dallas, Texas, United States, 75235
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Australia, New South Wales
The Children's Hospital at Westmead
Westmead, New South Wales, Australia, 2145
Sponsors and Collaborators
University of Alabama at Birmingham
Children's Hospital Boston
Children's Hospital Philadelphia
Children's Research Institute
Children's Hospital Medical Center, Cincinnati
University of Chicago
University of Utah
Washington University School of Medicine
The Children's Hospital at Westmead
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Kathryn North, MD University of Sydney - Westmead
Study Director: Maria Acosta, MD Children's Research Institute
Study Director: Jonathan Payne, MD University of Sydney - Westmead
  More Information

No publications provided

Responsible Party: Bruce Korf, MD, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00853580     History of Changes
Other Study ID Numbers: X080929007, DOD: W81XWH-05-1 0615
Study First Received: February 23, 2009
Last Updated: February 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
Neurofibromatosis Type 1, Neurocognitive, Phase II

Additional relevant MeSH terms:
Neurofibromatoses
Neurofibromatosis 1
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplastic Syndromes, Hereditary
Nerve Sheath Neoplasms
Nervous System Diseases
Neurocutaneous Syndromes
Neurodegenerative Diseases
Neurofibroma
Neuromuscular Diseases
Peripheral Nervous System Diseases
Lovastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014