Efficacy of Computerized Cognitive Training and Stimulant Medication in Neurofibromatosis Type 1

Not Applicable

Completed

• Conditions: Neurofibromatosis Type 1

• Registration Number: NCT02944032
• Lead Sponsor: Kristina Hardy

Brief Summary

The main objective of the study is to assess the efficacy of a home-based, computerized cognitive training (CT) program, called CogmedRM, targeted to improve working memory in children with NF1 and working memory difficulties. This is a Phase II randomized parallel group controlled clinical trial comparing two interventions on cognitive outcomes. Participants will be stratified by stimulant medication use and randomized equally between the two interventions within stratum. Participants will be in the study for to 11 weeks.

Detailed Description

Cognitive deficits are the most important cause of long-term dysfunction in patients with Neurofibromatosis type 1 (NF1). Among the most frequently-occurring difficulties are problems with attention, working memory (WM), and executive functioning (EF). Remediation and interventions to improve those deficits have the potential to impact the quality of life and long-term prognosis in this population. Cognitive training (CT) programs have increasingly been used independently or in conjunction with pharmacotherapies in children with accidental or disease-related brain injury. CogmedRM is both the most well-researched and widely-used CT program for remediation of WM deficits. Results from numerous randomized, controlled trials conducted with a variety of pediatric and adult patient populations generally show that CogmedRM training is associated with robust gains in performance-based WM scores over the short term, with some variability in improvement across disease groups. A single arm pilot study of CogmedRM in a sample of children with NF1 conducted at Children's National Medical Center has shown that the approach is likely feasible and acceptable to families.

Because many children with NF1 are treated with stimulant medications, and there is biological evidence that both CT and Methylphenidate act on dopaminergic systems, the investigators are also interested in examining whether or not there is a synergistic effect between these widely available and safe interventions. Thus, the aim is to assess the efficacy of a home-based, computerized cognitive training (CT) program in a sample of 90 children aged 8-16 with NF1 and working memory difficulties. This study will be conducted over the span of four years. If the participant qualifies following baseline testing, he/she will be randomized to the intervention, CogmedRM, or the active control condition, MobyMax (an online reading program). The participant will have 5-9 weeks to complete the program and will have follow-up testing 2 weeks after finishing the program. If CT, either singly or in combination with stimulant medication, can be shown to be efficacious in a sample of NF1 pediatric patients at high risk for neurocognitive deficits, this intervention plan could be rapidly translated to clinical practice.

Study Timeline

• Study Start: 2016-05
• Study First Submitted: 2016-05-25
• Study First Submitted QC: 2016-10-24
• Study First Posted: 2016-10-25
• Primary Completion: 2021-09-27
• Study Completion: 2021-09-27
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-02
• Last Update Posted: 2022-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 103

Inclusion Criteria

1. 8-16 years old at time of screening
2. NF1 Diagnosis based on National Institute of Health (NIH) criteria
3. Has an identified caregiver who is willing and able to oversee the training practice during the intervention period
4. Has access to a telephone and phone number where they can be reached
5. Both patient and caregiver have reading, speaking, and listening comprehension of English
6. Treated with a stable dose of stimulant medication for at least the last 30 days and not planning to change the dose during study participation or receiving no stimulant medications for at least the last 30 days and not planning to initiate a trial of stimulant medications for the duration of the study.
7. >1 Standard Deviation (SD) below the mean on the WISC-V-Integrated Spatial Span Backwards task or a Spatial Span Backwards score >1 SD below the participant's estimated IQ.

Exclusion Criteria

1. Full scale IQ<70, as estimated by WASI-II (Block Design, Vocabulary, Matrix Reasoning, Similarities).

   Note: In cases where there is a statistically significant difference between verbal IQ and performance IQ (.05 level as determined by the WASI-II manual), participants will be eligible if at least one of these quotients is 70 or above

2. Current treatment for intracranial lesions, progressive tumors as per MRI evaluation or treatment with chemotherapy within the past 6 months

3. A motor, visual, or auditory handicap that prevents computer use

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in CogState One-back subtest	From baseline to end of training, up to 11 weeks	Computerized task of working memory

Secondary Outcome Measures

Name	Time	Method
Change in Test of Word Reading Efficiency-Second Edition (TOWRE-2) Scores	From baseline to end of training, up to 11 weeks	Child-completed reading task
Change in Wechsler Intelligence Scale for Children-Fifth Edition-Integrated Spatial Span Backward	From baseline to end of training, up to 11 weeks	Visual-spatial working memory task
Change in Wechsler Intelligence Scale for Children-Fifth Edition-Integrated Digit Span Backward	From baseline to end of training, up to 11 weeks	Auditory working memory task
CogState One-card Learning	From baseline to end of training, up to 11 weeks	Computerized attention and executive functioning tasks
Change in Attention Deficit Hyperactive Disorder- Rating Scale	From baseline to end of training, up to 11 weeks	Parent-completed rating scale
Change in Wechsler Intelligence Scale for Children-Fifth Edition-Integrated Letter-Number Sequencing	From baseline to end of training, up to 11 weeks	Auditory working memory task
Change in Behavior Rating Inventory of Executive Functioning (BRIEF) Working Memory Index	From baseline to end of training, up to 11 weeks	Parent-completed questionnaire
Change in Test of Everyday Reading Comprehension (TERC) Scores	From baseline to end of training, up to 11 weeks	Child-completed reading task
Change in Behavior Rating Inventory of Executive Functioning (BRIEF) Metacognition Index	From baseline to end of training, up to 11 weeks	Parent-completed questionnaire
CogState Groton Maze Learning Task	From baseline to end of training, up to 11 weeks	Computerized task of executive functioning

Trial Locations

Locations (1)

Children's National Health System; 🇺🇸 Washington, District of Columbia, United States