A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1
STARS
2 other identifiers
interventional
146
2 countries
12
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2009
Longer than P75 for phase_2
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 23, 2009
CompletedFirst Posted
Study publicly available on registry
March 2, 2009
CompletedStudy Start
First participant enrolled
July 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2016
CompletedResults Posted
Study results publicly available
March 12, 2018
CompletedMarch 12, 2018
March 1, 2018
4.8 years
February 23, 2009
September 15, 2017
March 8, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Paired Associate Learning (Cambridge Neuropsychological Test Automated Battery).
A computerized test of visuospatial learning. Participants had to remember patterns associated with different locations on the screen, and during the test phase, as each pattern is presented, point to the appropriate location. The test starts at a very simple level and gradually increases in difficulty. Higher number of errors indicates poorer performance. Scale does not have a maximum range.
Baseline and Post-treatment (16 weeks)
Score! (Test of Everyday Attention for Children)
Score! is a measure of sustained attention. Participants were required to silently count a series of aurally presented tones and say the total number of tones counted at the end of each trial. The number of tones ranged from 9 to 15, with a total of 10 trials (range 0-10). Higher values represent better performance.
Baseline and Post-treatment (16 weeks)
Secondary Outcomes (18)
Spatial Working Memory (Cambridge Neuropsychological Test Automated Battery)
Baseline and Post-treatment (16 weeks)
Stockings of Cambridge (Cambridge Neuropsychological Test Automated Battery) Automated Battery).
Baseline and Post-treatment (16 weeks)
Stop Signal Task (Cambridge Neuropsychological Test Automated Battery)
Baseline and Post-treatment (16 weeks)
Sky Search (Test of Everyday Attention for Children)
Baseline and Post-treatment (16 weeks)
Sky Search DT (Test of Everyday Attention for Children)
Baseline and Post-treatment (16 weeks)
- +13 more secondary outcomes
Study Arms (2)
2
PLACEBO COMPARATORThis 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.
1
EXPERIMENTALThis 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.
Interventions
Lovastatin starting at 20mg for 2 weeks, increasing to 40mg for 14 weeks. Total duration of trial is 16 weeks.
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
You may qualify if:
- Males or females aged between 8 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. 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.
You may not qualify if:
- Full-scale IQ less than 70; In cases where this is a statistically significant difference between performance IQ and verbal IQ (.05 level), patients will be excluded if both quotients fall below 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 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Alabama at Birminghamlead
- Boston Children's Hospitalcollaborator
- Children's Hospital of Philadelphiacollaborator
- Children's National Research Institutecollaborator
- Children's Hospital Medical Center, Cincinnaticollaborator
- National Cancer Institute (NCI)collaborator
- University of Chicagocollaborator
- University of Utahcollaborator
- Washington University School of Medicinecollaborator
- Sydney Children's Hospitals Networkcollaborator
- University of Texas Southwestern Medical Centercollaborator
Study Sites (12)
The University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
University of Chicago
Chicago, Illinois, 60637, United States
NIH
Bethesda, Maryland, 20892, United States
Children' Hospital Boston
Boston, Massachusetts, 02115, United States
Washington University - St. Louis
St Louis, Missouri, 63110, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19096, United States
Childrens Medical Center - Univ. of Texas SW Medical Center
Dallas, Texas, 75235, United States
University of Utah
Salt Lake City, Utah, 84132, United States
The Children's Hospital at Westmead
Westmead, New South Wales, 2145, Australia
Related Publications (1)
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.
PMID: 27956565DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bruce R. Korf
- Organization
- The University of Alabama at Birmingham
Study Officials
- PRINCIPAL INVESTIGATOR
Kathryn North, MD
University of Sydney - Westmead
- STUDY DIRECTOR
Maria Acosta, MD
Children's National Research Institute
- STUDY DIRECTOR
Jonathan Payne, MD
University of Sydney - Westmead
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
February 23, 2009
First Posted
March 2, 2009
Study Start
July 1, 2009
Primary Completion
May 1, 2014
Study Completion
December 1, 2016
Last Updated
March 12, 2018
Results First Posted
March 12, 2018
Record last verified: 2018-03