A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1 (STARS)
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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 |
|---|---|---|
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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 |
- Visual Spatial Learning and Memory; Attention: *Score!; and TEA-Ch. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
- 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.
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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.
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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.
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Drug: Lovastatin ™
Lovastatin starting at 20mg for 2 weeks, increasing to 40mg for 14 weeks. Total duration of trial is 16 weeks.
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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 |
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| Contact: Bruce Korf, MD, PhD | 205.934.9411 | bkorf@uab.edu |
| Contact: Karen Cole-Plourde, BS | 205.934.5140 | kcole@uab.edu |
| United States, Alabama | |
| The University of Alabama at Birmingham | Recruiting |
| Birmingham, Alabama, United States, 35294 | |
| Contact: Bruce Korf, MD 205-934-9411 bkorf@uab.edu | |
| Contact: Christina Barger, MPH 205.934-9411 cbarger@genetics.uab.edu | |
| Principal Investigator: Bruce Korf, MD, PhD | |
| United States, District of Columbia | |
| Children's National Medical Center | Recruiting |
| Washington, District of Columbia, United States, 20010 | |
| Contact: Roger Packer, MD 202-884-2120 rpacker@cnmc.org | |
| Contact: Rochelle Kane 202.476.6485 RKanejac@cnmc.org | |
| Principal Investigator: Roger Packer, MD | |
| United States, Illinois | |
| University of Chicago | Recruiting |
| Chicago, Illinois, United States, 60637 | |
| Contact: James Tonsgard, MD 773-702-6488 tonsgard@midway.uchicago.edu | |
| Contact: Cynthia MacKenzie 773.702.6487 cmackenzie@peds.bsd.uchicago.edu | |
| Principal Investigator: James Tonsgard, MD | |
| United States, Maryland | |
| National Cancer Institute (NCI) | Not yet recruiting |
| Bethesda, Maryland, United States, 20892 | |
| Contact: Brigitte Widemann, MD 301-496-7387 widemannb@mail.nih.gov | |
| Contact: Andy Gillespie, RN 301.402.1848 gillesan@mail.nih.gov | |
| United States, Massachusetts | |
| Children' Hospital Boston | Recruiting |
| Boston, Massachusetts, United States, 02115 | |
| Contact: Nicole Ullrich, MD 617-355-3193 nicole.ullrich@childrens.harvard.edu | |
| Contact: Heather Spinney 617.355.2067 heather.spinney@childrens.harvard.edu | |
| United States, Missouri | |
| Washington University - St. Louis | Recruiting |
| St. Louis, Missouri, United States, 63110 | |
| Contact: David Gutmann, MD 314-362-7379 gutmann@neuro.wustl.edu | |
| Contact: Linda Murray 314.454.4240 'Murray_KW@kids.wustl.edu | |
| Principal Investigator: David Gutmann, MD | |
| United States, Ohio | |
| Cincinnati Children's Hospital Medical Center | Recruiting |
| Cincinnati, Ohio, United States, 45229 | |
| Contact: Elizabeth Schorry, MD 513-636-4760 Elizabeth.Schorry@cchmc.org | |
| Contact: Kristina Kruskamp 513.636.5336 Kristina.Kruskamp@cchmc.org | |
| Principal Investigator: Elizabeth Schorry, MD | |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | Recruiting |
| Philadelphia, Pennsylvania, United States, 19096 | |
| Contact: Michael Fisher, MD 215-590-5188 fisherm@email.chop.edu | |
| Contact: Ratnakar Patti 215.590.5188 ratnakarp@email.chop.edu | |
| Principal Investigator: Michael Fisher, MD | |
| United States, Texas | |
| Childrens Medical Center - Univ. of Texas SW Medical Center | Recruiting |
| Dallas, Texas, United States, 75235 | |
| Contact: Laura Klesse, MD, PhD 214-648-3986 Laura.Klesse@utsouthwestern.edu | |
| Contact: Natasha Anderson, BA, CCRC 214-456-6439 Natasha.Anderson@childrens.com | |
| United States, Utah | |
| University of Utah | Recruiting |
| Salt Lake City, Utah, United States, 84132 | |
| Contact: Dave Viskochil, MD 801-581-8943 dave.viskochil@hsc.utah.edu | |
| Contact: Heather Hanson 801.587.7689 Heather.Hanson@hsc.utah.edu | |
| Principal Investigator: John Carey, MD | |
| Australia, New South Wales | |
| The Children's Hospital at Westmead | Recruiting |
| Westmead, New South Wales, Australia, 2145 | |
| Contact: Kathryn North, MD 61-9845-1906 kathryN@chw.edu.au | |
| Contact: Jonathan Payne, MD 61.2.9845.3698 JonathaP@chw.edu.au | |
| Principal Investigator: Kathyrn North (Barton), MD | |
| 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: | April 25, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by University of Alabama at Birmingham:
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Neurofibromatosis Type 1, Neurocognitive, Phase II |
Additional relevant MeSH terms:
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Neurofibromatosis 1 Neurofibromatoses Osteitis Fibrosa Cystica 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 Bone Diseases, Endocrine Bone Diseases Musculoskeletal Diseases Lovastatin Hydroxymethylglutaryl-CoA Reductase Inhibitors Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Enzyme Inhibitors Lipid Regulating Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 19, 2013