A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1
10 Years
15 Years
Both
Neurofibromatosis Type 1
Trial Information
A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1
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.
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.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Outcome Measure:
Visual Spatial Learning and Memory; Attention: *Score!; and TEA-Ch.
Outcome Time Frame:
16 weeks
Safety Issue:
No
Principal Investigator
Kathryn North, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Sydney - Westmead
Authority:
United States: Institutional Review Board
Study ID:
X080929007
NCT ID:
NCT00853580
Start Date:
July 2009
Completion Date:
July 2014
Related Keywords:
- Neurofibromatosis Type 1
- Neurofibromatosis Type 1, Neurocognitive, Phase II
- Neurofibromatoses
- Neurofibromatosis 1
- Osteitis Fibrosa Cystica
Name | Location |
|---|---|
| The University of Alabama at Birmingham | Birmingham, Alabama 35294 |
| National Cancer Institute (NCI) | Bethesda, Maryland 20892 |
| Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
| Children's National Medical Center | Washington, District of Columbia 20010-2970 |
| Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
| Washington University - St. Louis | St. Louis, Missouri 63110 |
| University of Utah | Salt Lake City, Utah |
| University of Chicago | Chicago, Illinois 60637 |
| Children' Hospital Boston | Boston, Massachusetts 02115 |
| Childrens Medical Center - Univ. of Texas SW Medical Center | Dallas, Texas 75235 |
