Clinical trial NCT02944032: Efficacy of Computerized Cognitive Training and Stimulant Medication in Neurofibromatosis Type 1
Official title: Multimodal Intervention Trial for Cognitive Deficits in Neurofibromatosis Type 1: Efficacy of Computerized Cognitive Training and Stimulant Medication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Neurofibromatosis Type 1
Lead sponsor: Children's National Research Institute
Sponsor class: OTHER
Collaborators: name: Children's National Health System
name: Royal Children's Hospital
name: Children's Hospital Los Angeles
name: Sydney Children's Hospitals Network
First posted: 2016-10-25
Enrollment: 103
Sex: ALL
Minimum age (years): 8
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in CogState One-back subtest
timeFrame: From baseline to end of training, up to 11 weeks
Secondary outcomes:
measure: Change in Attention Deficit Hyperactive Disorder- Rating Scale
timeFrame: From baseline to end of training, up to 11 weeks
measure: Change in Wechsler Intelligence Scale for Children-Fifth Edition-Integrated Spatial Span Backward
timeFrame: From baseline to end of training, up to 11 weeks
measure: Change in Wechsler Intelligence Scale for Children-Fifth Edition-Integrated Digit Span Backward
timeFrame: From baseline to end of training, up to 11 weeks
measure: CogState One-card Learning
timeFrame: From baseline to end of training, up to 11 weeks
measure: Change in Behavior Rating Inventory of Executive Functioning (BRIEF) Working Memory Index
timeFrame: From baseline to end of training, up to 11 weeks
measure: Change in Test of Word Reading Efficiency-Second Edition (TOWRE-2) Scores
timeFrame: From baseline to end of training, up to 11 weeks
measure: Change in Test of Everyday Reading Comprehension (TERC) Scores
timeFrame: From baseline to end of training, up to 11 weeks
measure: Change in Behavior Rating Inventory of Executive Functioning (BRIEF) Metacognition Index
timeFrame: From baseline to end of training, up to 11 weeks
measure: CogState Groton Maze Learning Task
timeFrame: From baseline to end of training, up to 11 weeks
measure: Change in Wechsler Intelligence Scale for Children-Fifth Edition-Integrated Letter-Number Sequencing
timeFrame: From baseline to end of training, up to 11 weeks
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Health System
state: District of Columbia
Study officials:
affiliation: Children's National Health System
name: Kristina Hardy, PhD
role: PRINCIPAL_INVESTIGATOR
References: