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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00853580




Registration number
NCT00853580
Ethics application status
Date submitted
23/02/2009
Date registered
2/03/2009
Date last updated
12/03/2018

Titles & IDs
Public title
A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1
Scientific title
A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1
Secondary ID [1] 0 0
DOD: W81XWH-05-1 0615
Secondary ID [2] 0 0
X080929007
Universal Trial Number (UTN)
Trial acronym
STARS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neurofibromatosis Type 1 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Skin 0 0 0 0
Dermatological conditions
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lovastatin ™
Treatment: Devices - placebo

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 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.

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 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.


Treatment: Drugs: Lovastatin ™
Lovastatin starting at 20mg for 2 weeks, increasing to 40mg for 14 weeks. Total duration of trial is 16 weeks.

Treatment: Devices: placebo
Starting at 20mg for 2 weeks, then increasing to 40mg for 14 additional weeks for a total duration of treatment of 16 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Paired Associate Learning (Cambridge Neuropsychological Test Automated Battery).
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Baseline and Post-treatment (16 weeks)
Primary outcome [2] 0 0
Score! (Test of Everyday Attention for Children)
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Baseline and Post-treatment (16 weeks)
Secondary outcome [1] 0 0
Spatial Working Memory (Cambridge Neuropsychological Test Automated Battery)
Assessment method [1] 0 0
A computerized measure of spatial working memory. This task assessed the participant's ability to retain spatial information and to manipulate remembered items in working memory. In this test, participants were shown an array of boxes on a computer screen and they were required to search through the boxes for hidden tokens. One box at a time was touched until a blue token was found inside. Participants then commenced a new search for the next token. The key instruction was that, once a token had been located, that box would not be used again to hide another token. Unit of measure was between search errors, determined by the number of boxes a participant reopens in which a token had previously been found. Higher score indicated poorer performance. Scale does not have a maximum range.
Timepoint [1] 0 0
Baseline and Post-treatment (16 weeks)
Secondary outcome [2] 0 0
Stockings of Cambridge (Cambridge Neuropsychological Test Automated Battery) Automated Battery).
Assessment method [2] 0 0
A computerized measure of spatial planning based on the "Tower of London" test. It required participants to move balls in a lower display to match a pattern shown in the upper display in a certain number of moves. More specifically, the participant was shown two displays containing three coloured balls. The displays were presented in such a way that they could be perceived as stacks of coloured balls held in socks suspended from a beam. The test administrator first demonstrated to the participant how to move the balls in the lower display to copy the pattern in the upper display and completed one demonstration problem, where the solution required one move. The participant then completed problems that increased in difficulty, from one through to five move problems. The unit of measure was the mean number of moves taken to complete a problem that could not be completed in less than five moves. The higher the score, the poorer the performance (range 5-12).
Timepoint [2] 0 0
Baseline and Post-treatment (16 weeks)
Secondary outcome [3] 0 0
Stop Signal Task (Cambridge Neuropsychological Test Automated Battery)
Assessment method [3] 0 0
A computerized measure of inhibitory control. The participant quickly responded to an arrow stimulus by pressing one of two buttons (left or right), depending on the direction in which the arrow pointed on the screen. If an audio tone is present, the subject was supposed to withhold the response. The difficulty of the task was manipulated by altering the delay before a stop signal (auditory tone) was presented, known as the stop signal delay. The outcome from this measure was stop signal reaction time (last half of test), which was computed by subtracting the mean stop signal delay at which the participant was able to stop on 50% of trials from the mean reaction time on go trials. Poorer response inhibition was reflected by a larger stop signal reaction time. Scale does not have a maximum range.
Timepoint [3] 0 0
Baseline and Post-treatment (16 weeks)
Secondary outcome [4] 0 0
Sky Search (Test of Everyday Attention for Children)
Assessment method [4] 0 0
Sky Search is a measure of selective visual attention. Participants were presented with a A3 sheet with target stimuli (spaceships in identical pairs) randomly distributed among many distractors (spaceships in non-identical pairs). They were required to circle as many of the targets as possible as quickly as possible. The outcome measure (attention score), was a timing score reflecting the average time taken per target found. Higher scores represent poorer performance. Raw data are reported. Scale does not have a maximum range.
Timepoint [4] 0 0
Baseline and Post-treatment (16 weeks)
Secondary outcome [5] 0 0
Sky Search DT (Test of Everyday Attention for Children)
Assessment method [5] 0 0
Sky Search DT is a test of divided attention. Children completed a parallel version of the Sky Search subtest while at the same time, silently counted the number of tones in a similar way to the Score! subtest. Higher scores represent poorer performance. Raw data are reported. Scale does not have a maximum range.
Timepoint [5] 0 0
Baseline and Post-treatment (16 weeks)
Secondary outcome [6] 0 0
Creature Counting (Test of Everyday Attention for Children)
Assessment method [6] 0 0
Creature Counting is a measure of attentional control. Participants were required to count "creatures" from top of the page to the bottom, using arrows as cues to switch from counting up to counting down (and vice versa). There were seven testing trials. The outcome variable was the total number of correct trials (range 0-7). Higher scores represent better performances.
Timepoint [6] 0 0
Baseline and Post-treatment (16 weeks)
Secondary outcome [7] 0 0
Commission Errors (Conners Continuous Performance Test, Second Edition; CPT-II)
Assessment method [7] 0 0
A computerised measure of impulse control. Letters were presented serially on a screen in a random order. All letters were considered target stimuli, except for the letter 'X' which is a non-target stimulus. Participants responded to target stimuli by pressing the space bar of a computer keyboard (90% of the stimuli) while withholding responses to non-target stimuli (10% of the test). Commission errors represented the number of times a participant incorrectly responded to the non-target (letter 'X'). T-scores are reported, as generated by the test software. Higher scores indicate poorer performances.
Timepoint [7] 0 0
Baseline and Post-treatment (16 weeks)
Secondary outcome [8] 0 0
Omission Errors (Conners Continuous Performance Test, Second Edition; CPT-II)
Assessment method [8] 0 0
A computerised measure of vigilance and concentration. Letters were presented serially on a screen in a random order. All letters were considered target stimuli, except for the letter 'X' which is a non-target stimulus. Participants responded to target stimuli by pressing the space bar of a computer keyboard (90% of the stimuli) while withholding responses to non-target stimuli (10% of the test). Omission errors represented the number of times a participant fails to respond to target letters (all other than 'X'). T-scores are reported, as generated by the test software. Higher scores indicate poorer performances.
Timepoint [8] 0 0
Baseline and Post-treatment (16 weeks)
Secondary outcome [9] 0 0
ADHD Inattentive Scale, Conners ADHD Scales
Assessment method [9] 0 0
Parent rated inattentive ADHD symptoms, based on Diagnostic and Statistical Manual of Mental Disorders criteria, 4th edition. T-scores are reported. Higher scores indicate increased ADHD-related symptoms. A score below 60 is considered healthy, 61-65 a possible significant problem, and 66+ is considered a significant problem.
Timepoint [9] 0 0
Baseline and Post-treatment (16 weeks)
Secondary outcome [10] 0 0
ADHD Hyperactive/Impulsive Scale, Conners ADHD Scales
Assessment method [10] 0 0
Parent rated hyperactive/impulsive ADHD symptoms, based on Diagnostic and Statistical Manual of Mental Disorders criteria, 4th edition.T-scores are reported. Higher scores indicate increased ADHD-related symptoms. A score below 60 is considered healthy, 61-65 a possible significant problem, and 66+ is considered a significant problem.
Timepoint [10] 0 0
Baseline and Post-treatment (16 weeks)
Secondary outcome [11] 0 0
Controlled Oral Word Association Test
Assessment method [11] 0 0
A measure of verbal fluency. Participants were required to spontaneously produce as many words as they could, beginning with a designated letter in 60 seconds. Three letters were used. Higher scores represent better performances. Raw data are reported summing total words generated for all three letters. Scale does not have a maximum range.
Timepoint [11] 0 0
Baseline and Post-treatment (week 16)
Secondary outcome [12] 0 0
Judgement of Line Orientation Test
Assessment method [12] 0 0
A test of visuospatial judgement. The test measured the participant's ability to match the angle and orientation of lines in space. There were 30 trial in total. Correct response in a trial was awarded one point (range 0-30). Higher scores represent better performances. Raw data are reported.
Timepoint [12] 0 0
Baseline and Post-treatment (week 16)
Secondary outcome [13] 0 0
Behavior Rating Inventory of Executive Function Global Executive Composite
Assessment method [13] 0 0
A parent-rated questionnaire of executive behaviour assessing behavioral regulation (inhibit, shift, emotional control) and metacognition (initiate, working memory, plan/organize, organization of materials, self-monitoring). T-scores for the Global Executive Composite (overall summary score) are reported. Higher scores indicate poorer executive behaviors.
Timepoint [13] 0 0
Baseline and Post-treatment (week 16)
Secondary outcome [14] 0 0
Object Assembly (WISC-III)
Assessment method [14] 0 0
A measure of visuoperceptual organization. Participants were required to rebuild an item puzzle based on disassembled pieces. Age scaled scores are reported, which have a population mean of 10 and standard deviation of 3 (range 1-19). Higher scores indicate better performances.
Timepoint [14] 0 0
Baseline and Post-treatment (week 16)
Secondary outcome [15] 0 0
Internalizing Behaviors, Behavior Assessment System for Children Second Edition
Assessment method [15] 0 0
A parent-reported questionnaire assessing internalizing behaviors of anxiety, depression and somatization. T-scores are reported. Higher scores indicate increased internalizing behaviors. A score below 60 is considered healthy, 61-65 a possible significant problem, and 66+ is considered a significant problem.
Timepoint [15] 0 0
Baseline and Post-treatment (week 16)
Secondary outcome [16] 0 0
Internalizing Behaviors, Behavior Assessment System for Children Second Edition
Assessment method [16] 0 0
A self-reported questionnaire assessing internalizing behaviors such as anxiety and depression. T-scores are reported. Higher scores indicate increased internalizing behaviors. A score below 60 is considered healthy, 61-65 a possible significant problem, and 66+ is considered a significant problem.
Timepoint [16] 0 0
Baseline and Post-treatment (week 16)
Secondary outcome [17] 0 0
Quality of Life Pediatric Quality of Life Inventory (PedsQL)
Assessment method [17] 0 0
Parent-rated questionnaire of psychosocial Quality of Life (including emotional, social and school functioning). Summary scores are reported. Higher scores indicate increased increased quality of life (range 0-100).
Timepoint [17] 0 0
Baseline and Post-treatment (week 16)
Secondary outcome [18] 0 0
Psychosocial Quality of Life PedsQL
Assessment method [18] 0 0
Self-rated questionnaire of psychosocial Quality of Life (including emotional, social and school functioning). Summary scores are reported. Higher scores indicate higher quality of life (range 0-100).
Timepoint [18] 0 0
Baseline and Post-treatment (week 16)

Eligibility
Key inclusion criteria
* 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.
Minimum age
8 Years
Maximum age
15 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2016
Sample size
Target
Accrual to date
Final
146
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Utah

Funding & Sponsors
Primary sponsor type
Other
Name
University of Alabama at Birmingham
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Boston Children's Hospital
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Children's Hospital of Philadelphia
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Children's National Research Institute
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Children's Hospital Medical Center, Cincinnati
Country [4] 0 0
Other collaborator category [5] 0 0
Government body
Name [5] 0 0
National Cancer Institute (NCI)
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
University of Chicago
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
University of Utah
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
Washington University School of Medicine
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
Sydney Children's Hospitals Network
Country [9] 0 0
Other collaborator category [10] 0 0
Other
Name [10] 0 0
University of Texas Southwestern Medical Center
Country [10] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Kathryn North, MD
Address 0 0
University of Sydney - Westmead
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol
Statistical analysis plan
Informed consent form



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00853580