None listed
Conditions
Brief summary
The specific aim of this study is to determine whether methylphenidate significantly reduces deficits in attention and/or executive function in children with NF1. This study also aims to establish whether MPH reduces ADHD related behaviours in neurofibromatosis. It is hypothesised that methylphenidate will improve attention and executive function deficits in children with NF1 and reduce the ADHD like behavioural characteristics in children with NF1.
Interventions
Part 1
Methylphenidate will be the active substance in the first phase of this trial. This part of the trial will be a randomised placebo controlled cross over trial with a duration of 12 weeks (6 weeks of active substance, 6 weeks of placebo). Methylphenidate dose level will be up to 1.5mg/kg a day. Dose level will not exceed 60mg/day. The appropriate dose level for each subject will be determined during a 2 week titration phase. Methylphenidate powder will be presented as a crushed powder in
Part 1 Methylphenidate will be the active substance in the first phase of this trial. This part of the trial will be a randomised placebo controlled cross over trial with a duration of 12 weeks (6 weeks of active substance, 6 weeks of placebo). Methylphenidate dose level will be up to 1.5mg/kg a day. Dose level will not exceed 60mg/day. The appropriate dose level for each subject will be determined during a 2 week titration phase. Methylphenidate powder will be presented as a crushed powder in opaque gelatin capsules containing either 5mg methylphendiate or 10mg methylphenidate. Treatment phase duration is 4 weeks. Capsules will need to be taken orally three times a day. No washout period between the active arm and the placebo arm exists. Part 2 (open label) Methylphenidate (Ritalin LA capsules) 10mg/20mg/30mg/40mg. If a participant demonstrates a significant reliable improvement in any of the primary outcome measures after they have completed Part 1 of the trial (i.e. completed both 6 weeks of methylphenidate and 6 weeks of placebo) he/she will be invited to immediately continue on methylphenidate (Ritalin long acting) for 13 weeks (or until 6 months after her/his baseline assessment). The dose level of Ritalin long acting will be different for each participant and will be equivalent to his/her dose level of active substance in Part 1 of the trial. Participants will be required to take this dose level once in the morning on daily basis.
Sponsors
The Children's Hospital at Westmead
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
7 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
1. All participants must fulfil the diagnosis of NF1 based on NIH criteria (NIH, 2000); 2. Participants must have a full scale IQ greater than or equal to 70 or if a significant discrepancy is present between PRI and VCI the higher will be used. This index used must be 70 or above; 3. Participants’ behaviour must be rated as abnormal by their parent on the Conners 3. An abnormal score is defined as a T score equal to or greater than 65 on the following scales inattention, hyperactivity/impulsivity. 4. Participants must have a cognitive impairment defined as having a score of at least one standard deviation or more below the population mean on at least one of the primary objective outcome measures: a) Conner’s Continuous Performance Test –II (CPT II Omissions) b) CANTAB Spatial Working Memory (SWM) (between errors total).
Exclusion criteria
1. Participants who have intracranial pathology such as epilepsy, hydrocephalus, diagnosed traumatic brain injury, or progressive intracranial tumours (children with asymptomatic or static lesions will be eligible); 2. Children who have significant visual and/or hearing problems; 3. Children who have contraindications to stimulant medication. These include those with glaucoma, hypertension, previous insensitivity to stimulant medication or are on contraindicated medication such as monoamine oxidase (MAO) inhibitors; 4. Children with Tourette’s syndrome, tics, or other major psychiatric disorders; 5. Female participants of childbearing age should not be pregnant, must have a negative urine pregnancy test before initiation of treatment; 6. Children who have received any investigational drugs of any type within 30 days of initiation of study; 7. Children with a co-existing medical condition that is likely to interfere or who are taking any concomitant medication that is likely to interfere with safe administration of methylphenidate in the investigators opinion. 8. Children who are requiring any of the following medications: clonidine or other alpha2 adrenergic receptor agonists, tricyclic antidepressants, selective serotonin reuptake inhibitors, theophylline, coumarin, or anticonvulsants. 9. Children who have blood pressure measurements (systolic or diastolic) equal to or greater than 95th percentile for age, sex and height at screening. 10. Children who require drug therapy or hospitalisation for treatment of a mood disorder or anxiety disorder. 11. Children with ECG abnormalities that are deemed clinically significant 12. Children with drug or alcohol abuse or dependence within the prior six months 13. Children who are currently on stimulant medication for ADHD before the trial will be required to undergo a 3 week washout period prior to the screening assessment to minimise any potential carry over effects of the drug and allow the parents and teachers to complete the behavioural questionnaire based on the child's off medication behaviour.
Outcome results
None listed