Efficacy of Methylphenidate Treatment in Children with Neurofibromatosis type 1 (NF1): A randomised, placebo controlled, cross over trial

Phase 2

Recruiting

• Conditions: eurofibromatosis type 1; Neurofibromatosis type 1; Human Genetics and Inherited Disorders - Other human genetics and inherited disorders; Neurological - Other neurological disorders

• Registration Number: ACTRN12611000765921
• Lead Sponsor: The Children's Hospital at Westmead

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-07-21
• Last Update Posted: 3 October 2022

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 36

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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Cambridge Neuropsychological Testing Automated Battery (CANTAB) Spatial Working Memory Task. The number of between errors will be the outcome measure for this subtest.[Baseline (before treatment)<br>After 6 weeks of treatment<br>After 6 weeks of placebo<br>6 months from baseline];The Conners Continous Performance Test-II (CPT-II) Omission errors will be the outcome measure for this subtest[Baseline (before treatment)<br>After 6 weeks of treatment<br>After 6 weeks of placebo<br>6 months from baseline];The Conners 3 parent questionnaire. The outcome measures will be inattentive and hyperactive/impulsivity scale (T scores).[Baseline (before treatment)<br>After 6 weeks of treatment<br>After 6 weeks of placebo<br>6 months from baseline]