Neurofibromatosis Type 1Phase 2STARSNCT00853580
A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1
A Phase 2 study testing Lovastatin ™ in people with Neurofibromatosis Type 1, run by University of Alabama at Birmingham at 12 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 8 to 15 yearsHealthy volunteers can take part
- Conditions the study is for
- Neurofibromatosis Type 1
- What is being tested?
- Lovastatin ™
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 146 participants
- Where
- 12 sitesin 2 countries
- Study dates
- Jul 2009to Dec 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 15 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
United States11 sites
NIH
Bethesda, Maryland, 20892
The University of Alabama at Birmingham
Birmingham, Alabama, 35294
Children' Hospital Boston
Boston, Massachusetts, 02115
University of Chicago
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Childrens Medical Center - Univ. of Texas SW Medical Center
Dallas, Texas, 75235
Children's Hospital Los Angeles
Los Angeles, California, 90027
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19096
University of Utah
Salt Lake City, Utah, 84132
Washington University - St. Louis
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Australia1 site
The Children's Hospital at Westmead
Westmead, New South Wales, 2145
About this study
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:
Read more
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.
Read the 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 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
- Neurofibromatosis Type 1
- Being tested
- Lovastatin ™, placebo
- Keywords
- Neurofibromatosis Type 1, Neurocognitive, Phase II
- Medical subject headings
- Neurofibromatosis 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lovastatin ™Drug
Lovastatin starting at 20mg for 2 weeks, increasing to 40mg for 14 weeks. Total duration of trial is 16 weeks.
placeboDevice
Starting at 20mg for 2 weeks, then increasing to 40mg for 14 additional weeks for a total duration of treatment of 16 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 2 | Placebo comparator | 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. Receives: Device: placebo |
| 1 | Experimental | 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. Receives: Drug: Lovastatin ™ |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline and Post-treatment (16 weeks)
Secondary outcomes (18)
Spatial Working Memory (Cambridge Neuropsychological Test Automated Battery)
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.
Measured: Baseline and Post-treatment (16 weeks)
Stockings of Cambridge (Cambridge Neuropsychological Test Automated Battery) Automated Battery).
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).
Measured: Baseline and Post-treatment (16 weeks)
Stop Signal Task (Cambridge Neuropsychological Test Automated Battery)
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.
Measured: Baseline and Post-treatment (16 weeks)
Sky Search (Test of Everyday Attention for Children)
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.
Measured: Baseline and Post-treatment (16 weeks)
Sky Search DT (Test of Everyday Attention for Children)
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.
Measured: Baseline and Post-treatment (16 weeks)
Creature Counting (Test of Everyday Attention for Children)
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.
Measured: Baseline and Post-treatment (16 weeks)
Commission Errors (Conners Continuous Performance Test, Second Edition; CPT-II)
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.
Measured: Baseline and Post-treatment (16 weeks)
Omission Errors (Conners Continuous Performance Test, Second Edition; CPT-II)
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.
Measured: Baseline and Post-treatment (16 weeks)
ADHD Inattentive Scale, Conners ADHD Scales
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.
Measured: Baseline and Post-treatment (16 weeks)
ADHD Hyperactive/Impulsive Scale, Conners ADHD Scales
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.
Measured: Baseline and Post-treatment (16 weeks)
Controlled Oral Word Association Test
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.
Measured: Baseline and Post-treatment (week 16)
Judgement of Line Orientation Test
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.
Measured: Baseline and Post-treatment (week 16)
Behavior Rating Inventory of Executive Function Global Executive Composite
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.
Measured: Baseline and Post-treatment (week 16)
Object Assembly (WISC-III)
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.
Measured: Baseline and Post-treatment (week 16)
Internalizing Behaviors, Behavior Assessment System for Children Second Edition
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.
Measured: Baseline and Post-treatment (week 16)
Internalizing Behaviors, Behavior Assessment System for Children Second Edition
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.
Measured: Baseline and Post-treatment (week 16)
Quality of Life Pediatric Quality of Life Inventory (PedsQL)
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).
Measured: Baseline and Post-treatment (week 16)
Psychosocial Quality of Life PedsQL
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).
Measured: Baseline and Post-treatment (week 16)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2009 (estimated)
- Study startJul 2009
- Primary completionMay 2014
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neurofibromatosis Type 1Studies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 146 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Boston Children's Hospital, Children's Hospital of Philadelphia, Children's National Research Institute, Children's Hospital Medical Center, Cincinnati, National Cancer Institute (NCI), University of Chicago, University of Utah, Washington University School of Medicine, Sydney Children's Hospitals Network, University of Texas Southwestern Medical Center
- Responsible party
- Principal investigator, Bruce Korf, MD, University of Alabama at Birmingham
- Investigators
- Kathryn North, MD, Principal investigator, University of Sydney - WestmeadMaria Acosta, MD, Study director, Children's National Research InstituteJonathan Payne, MD, Study director, University of Sydney - Westmead
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00853580
- Sponsor's protocol ID
- X080929007
- Other IDs
- DOD: W81XWH-05-1 0615
- Acronym
- STARS
- Status last verified
- Mar 2018
- First submitted
- 23 Feb 2009
- Last updated
- 12 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 27956565
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1
- ClinicalTrials.gov ID
- NCT00853580
- Acronym / sponsor ID
- STARS / X080929007
- Conditions
- Neurofibromatosis Type 1
- Keywords
- Neurofibromatosis Type 1, Neurocognitive, Phase II
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 146 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Boston Children's Hospital, Children's Hospital of Philadelphia, Children's National Research Institute, Children's Hospital Medical Center, Cincinnati, National Cancer Institute (NCI), University of Chicago, University of Utah, Washington University School of Medicine, Sydney Children's Hospitals Network, University of Texas Southwestern Medical Center
- Study start
- Jul 2009
- Primary completion
- May 2014 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 2 Mar 2009 (estimated)
- Results
- Posted 12 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2 | Placebo comparator | Device: placeboThis 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 | Experimental | Drug: Lovastatin ™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. |
Who may qualify
- Ages
- 8 to 15 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lovastatin ™Lovastatin starting at 20mg for 2 weeks, increasing to 40mg for 14 weeks. Total duration of trial is 16 weeks. | Drug | 1 |
| placeboStarting at 20mg for 2 weeks, then increasing to 40mg for 14 additional weeks for a total duration of treatment of 16 weeks. | Device | 2 |
Primary outcome
Paired Associate Learning (Cambridge Neuropsychological Test Automated Battery).
Time frame: Baseline and Post-treatment (16 weeks)
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.
Score! (Test of Everyday Attention for Children)
Time frame: Baseline and Post-treatment (16 weeks)
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.
18 secondary outcomes
Spatial Working Memory (Cambridge Neuropsychological Test Automated Battery)
Time frame: Baseline and Post-treatment (16 weeks)
Stockings of Cambridge (Cambridge Neuropsychological Test Automated Battery) Automated Battery).
Time frame: Baseline and Post-treatment (16 weeks)
Stop Signal Task (Cambridge Neuropsychological Test Automated Battery)
Time frame: Baseline and Post-treatment (16 weeks)
Sky Search (Test of Everyday Attention for Children)
Time frame: Baseline and Post-treatment (16 weeks)
Sky Search DT (Test of Everyday Attention for Children)
Time frame: Baseline and Post-treatment (16 weeks)
Creature Counting (Test of Everyday Attention for Children)
Time frame: Baseline and Post-treatment (16 weeks)
Commission Errors (Conners Continuous Performance Test, Second Edition; CPT-II)
Time frame: Baseline and Post-treatment (16 weeks)
Omission Errors (Conners Continuous Performance Test, Second Edition; CPT-II)
Time frame: Baseline and Post-treatment (16 weeks)
ADHD Inattentive Scale, Conners ADHD Scales
Time frame: Baseline and Post-treatment (16 weeks)
ADHD Hyperactive/Impulsive Scale, Conners ADHD Scales
Time frame: Baseline and Post-treatment (16 weeks)
Controlled Oral Word Association Test
Time frame: Baseline and Post-treatment (week 16)
Judgement of Line Orientation Test
Time frame: Baseline and Post-treatment (week 16)
Behavior Rating Inventory of Executive Function Global Executive Composite
Time frame: Baseline and Post-treatment (week 16)
Object Assembly (WISC-III)
Time frame: Baseline and Post-treatment (week 16)
Internalizing Behaviors, Behavior Assessment System for Children Second Edition
Time frame: Baseline and Post-treatment (week 16)
Internalizing Behaviors, Behavior Assessment System for Children Second Edition
Time frame: Baseline and Post-treatment (week 16)
Quality of Life Pediatric Quality of Life Inventory (PedsQL)
Time frame: Baseline and Post-treatment (week 16)
Psychosocial Quality of Life PedsQL
Time frame: Baseline and Post-treatment (week 16)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27956565Payne 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathryn North, MD principal investigator
University of Sydney - Westmead
Maria Acosta, MD study director
Children's National Research Institute
Jonathan Payne, MD study director
University of Sydney - Westmead
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lovastatin ™ in people with Neurofibromatosis Type 1, run by University of Alabama at Birmingham at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Paired Associate Learning (Cambridge Neuropsychological Test Automated Battery). (time frame: Baseline and Post-treatment (16 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00853580, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2018.