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Trial registered on ANZCTR


Registration number
ACTRN12607000560493
Ethics application status
Approved
Date submitted
23/10/2007
Date registered
1/11/2007
Date last updated
25/02/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised placebo-controlled study of lovastatin in children with neurofibromatosis type 1
Scientific title
A prospective randomized placebo-controlled study to evaluate the effect of lovastatin on neuropsychological function in children with neurofibromatosis type 1
Secondary ID [1] 288620 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
STAtin Randomised Study: STARS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neurofibromatosis type 1 2329 0
Neuropsychological impairment 2330 0
Condition category
Condition code
Human Genetics and Inherited Disorders 2546 2546 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
We will evaluate the efficacy of lovastatin, a 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMG-CoA reductase) inhibitor, on visual spatial learning and sustained attention. Children in the treatment condition will initally take a titrated dose of lovastatin (20mg/day) for 2 weeks, followed by 40mg of lovastatin once per day for 14 weeks.
Intervention code [1] 2172 0
Treatment: Drugs
Comparator / control treatment
A placebo pill that is designed to be indistinguishable from lovastatin. It is plausible and ethical to employ a placebo as no standard therapy with established efficacy is withheld.
Control group
Placebo

Outcomes
Primary outcome [1] 3329 0
Visuospatial learning: Mean Total Errors Adjusted score on the "Paired Associate Learning" subtest from the Cambridge Neuropsychological Test Automated Battery (CANTAB).
Timepoint [1] 3329 0
Baseline, post-treatment (16 weeks after commencement of intervention) and 8 weeks after cessation of intervention.
Primary outcome [2] 3330 0
Sustained attention: Mean score on "Score!" subtest of the Test of Everyday Attention for Children (TEA-Ch).
Timepoint [2] 3330 0
Baseline, post-treatment (16 weeks after commencement of intervention) and 8 weeks after cessation of intervention.
Secondary outcome [1] 5540 0
Mean Total Errors from the "Spatial Working Memory" subtest from the CANTAB
Timepoint [1] 5540 0
Baseline, post-treatment (16 weeks after commencement of intervention) and 8 weeks after cessation of intervention.
Secondary outcome [2] 5541 0
Problems solved in minimum moves from the "Stockings of Cambridge" subtest from the CANTAB
Timepoint [2] 5541 0
Baseline, post-treatment (16 weeks after commencement of intervention) and 8 weeks after cessation of intervention.
Secondary outcome [3] 5542 0
The "Stop Signal Task" from the CANTAB
Timepoint [3] 5542 0
Baseline, post-treatment (16 weeks after commencement of intervention) and 8 weeks after cessation of intervention.
Secondary outcome [4] 5740 0
"Motor Screening" from the CANTAB
Timepoint [4] 5740 0
Baseline, post-treatment (16 weeks after commencement of intervention) and 8 weeks after cessation of intervention.
Secondary outcome [5] 5752 0
Judgement of Line Orientation
Timepoint [5] 5752 0
Baseline, post-treatment (16 weeks after commencement of intervention) and 8 weeks after cessation of intervention.
Secondary outcome [6] 5753 0
Total words on the "Controlled Oral Word Association Test".
Timepoint [6] 5753 0
Baseline, post-treatment (16 weeks after commencement of intervention) and 8 weeks after cessation of intervention.
Secondary outcome [7] 5754 0
Attention Score from the "Sky Search" subtest from the TEA-Ch
Timepoint [7] 5754 0
Baseline, post-treatment (16 weeks after commencement of intervention) and 8 weeks after cessation of intervention.
Secondary outcome [8] 5755 0
Dual Task Decrement from the "Sky Search DT" subtest from the TEA-Ch
Timepoint [8] 5755 0
Baseline, post-treatment (16 weeks after commencement of intervention) and 8 weeks after cessation of intervention.
Secondary outcome [9] 5756 0
Total Correct and Timing Score from the "Creature Counting" subtest from the TEA-Ch
Timepoint [9] 5756 0
Baseline, post-treatment (16 weeks after commencement of intervention) and 8 weeks after cessation of intervention.
Secondary outcome [10] 5757 0
Conners' Continuous Performance Test - II
Timepoint [10] 5757 0
Baseline, post-treatment (16 weeks after commencement of intervention) and 8 weeks after cessation of intervention.
Secondary outcome [11] 5758 0
Questionnaires: Conners ADHD/DSM-IV Scales (CADS; Parent Report); Behavior Rating Inventory of Executive Function (Parent Form), Behavior Assessment System for Children - II (Parent Report & Self Report), The Pediatric Quality of Life Scale (Parent Report & Self Report).
Timepoint [11] 5758 0
Baseline, post-treatment (16 weeks after commencement of intervention) and 8 weeks after cessation of intervention.

Eligibility
Key inclusion criteria
1. Males or females aged between 8-15 years of age who meet National Institutes of Health (NIH) diagnostic criteria for neurofibromatosis type 1 (NF1). 2. Full scale intellectual quotient (IQ) of 70 or above. 3. Cognitive impairment defined as having a score of at least 1 standard deviation or more below the normative mean on one or more of the primary outcome measures.
Minimum age
8 Years
Maximum age
15 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Full scale IQ score less than 70.
2. Individuals with insufficient English to complete the assessments.
3. Participants taking stimulant medication or Straterra, as it is unclear whether lovastatin and ADHD medication utilise similar biological pathways, possibly leading to an interaction between the two medications
4. Participants on psychotropic or antiepileptic medication
5. Participants with intracranial pathology such as epilepsy, diagnosed head injury, hydrocephalus or progressive intracranial tumors (children with asymptomatic or static lesions will be eligible).
6. Participants who are pregnant or breastfeeding.
7. Participants with a clinically significant unrelated illness, which in the judgement of the principle 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.
8. Children with very low LDL cholesterol levels pre-treatment (1 mmol/L). LDL levels within the normal range are required pre-treatment as lovastatin has been shown to lower levels of LDL cholesterol by approximately 30%.

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)
If the potential participant and his/her family are interested in participating in the study, they will undergo a screening assessment to determine eligability.

Once enrolled, participants will be allocated to a treatment condition by contacting the holder of the allocation schedule who is at a central administration site. Allocation will be concealed from clinical centre personnel(except pharmacy).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be by permuted block.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
An interim analysis will be conducted when there are 30 participants in each treatment arm. This analysis will be conducted to internally validate the adequacy of the sample size and to recalculate the sample size required if the treatment difference is smaller than expected. If the treatment effect is smaller than expected, large numbers of participants will be required to show that the treatment effect is statistically significant. However, if the treatment difference is larger than expected, it is usual to maintain the initial sample size calculation to ensure precision around the estimates. For example, a large effect size that occurs when the sample size is small may be an early random event.
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/07/2009
Actual
1/07/2009
Date of last participant enrolment
Anticipated
1/05/2014
Actual
1/05/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
142
Accrual to date
Final
146
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 455 0
2145
Recruitment outside Australia
Country [1] 589 0
United States of America
State/province [1] 589 0
45229
Country [2] 590 0
United States of America
State/province [2] 590 0
63110
Country [3] 591 0
United States of America
State/province [3] 591 0
84132
Country [4] 592 0
United States of America
State/province [4] 592 0
02115
Country [5] 593 0
United States of America
State/province [5] 593 0
19104
Country [6] 594 0
United States of America
State/province [6] 594 0
60637
Country [7] 595 0
United States of America
State/province [7] 595 0
35294
Country [8] 596 0
United States of America
State/province [8] 596 0
20010

Funding & Sponsors
Funding source category [1] 2693 0
Other
Name [1] 2693 0
US Army Medical Research and Materiel Command
Country [1] 2693 0
United States of America
Primary sponsor type
Individual
Name
Prof Kathryn North
Address
Murdoch Childrens Research Institute
Flemington Road Parkville
VIC 3052 Australia
Country
Australia
Secondary sponsor category [1] 2437 0
Individual
Name [1] 2437 0
Dr Jonathan Payne
Address [1] 2437 0
Neurogenetics Research Unit
The Children's Hospital at Westmead,
Locked Bag 4001, Westmead, 2145
Country [1] 2437 0
Australia
Secondary sponsor category [2] 2440 0
Individual
Name [2] 2440 0
Dr Belinda Barton
Address [2] 2440 0
Children's Hospital Education Research Institute
The Children's Hosptial at Westmead,
Locked Bag 4001, Westmead, 2145
Country [2] 2440 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4613 0
Royal Alexandra Hospital for Children Ethics Committee
Ethics committee address [1] 4613 0
Ethics committee country [1] 4613 0
Australia
Date submitted for ethics approval [1] 4613 0
26/09/2007
Approval date [1] 4613 0
18/12/2008
Ethics approval number [1] 4613 0
07/CHW/13

Summary
Brief summary
Children with neurofibromatosis type 1 (NF1) frequently demonstrate impairments in attention and visuospatial learning. Despite the significant negative impact of this disorder on cognitive functioning, no studies have examined the effects of interventions on the cognitive functioning of children with NF1.

Mice mutated at the NF1 gene provide a useful experimental model to study the biological basis of cognitive deficits in NF1 as they exhibit cognitive impairments that appear to mimic those displayed in children with NF1. Recent evidence has shown that the pharmacological agent lovastatin can reverse attention and learning deficits in NF1 mice. Lovastatin has a 20 year history as in treating hyperlipidemia and Phase I data in children with NF1 suggests that it is safe and tolerable. We intend to conduct a multi-centre, randomised trial examining the efficacy of lovastatin in children with NF1. There will be two treatment groups: one on lovastatin and the other a placebo control. The primary aim will be to establish whether lovastatin significantly improves visuospatial learning and/or sustained attention in children with NF1. Secondary aims include examining the effect of lovastatin on measures of executive function, behaviour and quality of life, as well as further evaluating the toxicity and tolerability of lovastatin in children with NF1.
Trial website
Trial related presentations / publications
Nil
Public notes

Contacts
Principal investigator
Name 28027 0
Prof Kathryn North
Address 28027 0
Murdoch Childrens Research Institute
Flemington Road PARKVILLE VIC 3052
Country 28027 0
Australia
Phone 28027 0
+61 3 8341 6226
Fax 28027 0
Email 28027 0
[email protected]
Contact person for public queries
Name 11184 0
Dr Jonathan Payne
Address 11184 0
Neurogenetics Research Unit
The Children's Hospital at Westmead
Locked Bag 4001, Westmead, 2145
Country 11184 0
Australia
Phone 11184 0
+61 2 9845 3698
Fax 11184 0
Email 11184 0
[email protected]
Contact person for scientific queries
Name 2112 0
Prof Kathryn North
Address 2112 0
Murdoch Childrens Research Institute
Flemington Road PARKVILLE VIC 3052
Country 2112 0
Australia
Phone 2112 0
+61 2 9845 1903
Fax 2112 0
Email 2112 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseRandomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1.2016https://dx.doi.org/10.1212/WNL.0000000000003435
N.B. These documents automatically identified may not have been verified by the study sponsor.