A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1
NCT ID: NCT00853580
Last Updated: 2018-03-12
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
146 participants
INTERVENTIONAL
2009-07-31
2016-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Selumetinib Paediatric NF1 Japan Study
NCT04495127
Ophthalmological Screening and Follow-up of Optic Pathway Gliomas in Children With Neurofibromatosis Type 1.
NCT02078401
Phase I Clinical Study of the Safety of Photodynamic Therapy (PDT) Using LS11 in Children With Plexiform Neurofibromas
NCT00716469
Liver MRI With Primovist/Eovist in Pediatric Subjects Who Are Suspected or Have Focal Liver Lesions.
NCT01043523
Identification of Pre-Malignant Lesions In Pediatric Patients With Neurofibromatosis Type 1 Using Novel Magnetic Resonance Imaging Techniques Paired With Artificial Intelligence
NCT04763109
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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 8 and less than 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 8 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 8 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 8 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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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 8 and less than 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.
placebo
Starting at 20mg for 2 weeks, then increasing to 40mg for 14 additional weeks for a total duration of treatment of 16 weeks.
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 8 and less than 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.
Lovastatin ™
Lovastatin starting at 20mg for 2 weeks, increasing to 40mg for 14 weeks. Total duration of trial is 16 weeks.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Lovastatin ™
Lovastatin starting at 20mg for 2 weeks, increasing to 40mg for 14 weeks. Total duration of trial is 16 weeks.
placebo
Starting at 20mg for 2 weeks, then increasing to 40mg for 14 additional weeks for a total duration of treatment of 16 weeks.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Participants must have a full-scale IQ of 70 or above. In cases where there is a statistically significant difference between verbal IQ and performance IQ (.05 level as determined by Table B3 in the WASI manual), participants will be eligible if at least one of these quotients is 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 who are on a stable dose of methylphenidate and/or dextroamphetamines for at least one month prior to screening and who will remain on the same dose for the duration of the study.
* 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
* 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 psychotropic medication other than methylphenidate and/or dextroamphetamines. These patients are eligible if, as clinically indicated, they cease medication for at least 30 days prior to screening and remain off these medication for the duration of the study
* 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 drug, other than sirolimus, within 30 days of initiation of study
* Participants who have recently taken Lovastatin. These participants will be eligible after a washout period of at least three months.
* 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 90mg/dl)
* Participants who have recently taken sirolimus within three months of enrollment. These participants will be eligible after a washout period of at least three months.
8 Years
15 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Boston Children's Hospital
OTHER
Children's Hospital of Philadelphia
OTHER
Children's National Research Institute
OTHER
Children's Hospital Medical Center, Cincinnati
OTHER
National Cancer Institute (NCI)
NIH
University of Chicago
OTHER
University of Utah
OTHER
Washington University School of Medicine
OTHER
Sydney Children's Hospitals Network
OTHER
University of Texas Southwestern Medical Center
OTHER
University of Alabama at Birmingham
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Bruce Korf, MD
Principal Investigator
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Kathryn North, MD
Role: PRINCIPAL_INVESTIGATOR
University of Sydney - Westmead
Maria Acosta, MD
Role: STUDY_DIRECTOR
Children's National Research Institute
Jonathan Payne, MD
Role: STUDY_DIRECTOR
University of Sydney - Westmead
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
The University of Alabama at Birmingham
Birmingham, Alabama, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
University of Chicago
Chicago, Illinois, United States
NIH
Bethesda, Maryland, United States
Children' Hospital Boston
Boston, Massachusetts, United States
Washington University - St. Louis
St Louis, Missouri, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Childrens Medical Center - Univ. of Texas SW Medical Center
Dallas, Texas, United States
University of Utah
Salt Lake City, Utah, United States
The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Payne JM, Barton B, Ullrich NJ, Cantor A, Hearps SJ, Cutter G, Rosser T, Walsh KS, Gioia GA, Wolters PL, Tonsgard J, Schorry E, Viskochil D, Klesse L, Fisher M, Gutmann DH, Silva AJ, Hunter SJ, Rey-Casserly C, Cantor NL, Byars AW, Stavinoha PL, Ackerson JD, Armstrong CL, Isenberg J, O'Neil SH, Packer RJ, Korf B, Acosta MT, North KN; NF Clinical Trials Consortium. Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1. Neurology. 2016 Dec 13;87(24):2575-2584. doi: 10.1212/WNL.0000000000003435. Epub 2016 Nov 9.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
DOD: W81XWH-05-1 0615
Identifier Type: OTHER
Identifier Source: secondary_id
X080929007
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.