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