Multimodal Intervention Trial for Cognitive Deficits in Neurofibromatosis Type 1: Efficacy of Computerized Cognitive Training and Stimulant Medication

Principal Investigator: HARDY, KRISTINA
Program: NFRP
Proposal Number: NF140033
Award Number: W81XWH-15-1-0508
Funding Mechanism: Clinical Trial Award
Partnering Awards:
Award Amount: $1,286,818.00


Children with Neurofibromatosis type 1 (NF1) often develop problems with learning, attention, and other thinking skills. These problems can make it more difficult for them to learn at school, get along with people, and be successful in daily activities. Scientists have shown that some of these difficulties with thinking are related to the way that a substance called dopamine is used in the brain. We believe that treatments that improve the way that dopamine works in the brain could help the thinking and learning skills of children and teenagers with NF1.

We are interested in studying two treatments that can affect dopamine in the brain. One treatment is a medicine, called methylphenidate (MPH). MPH is already used by many children, with and without NF1, to improve problems with attention. MPH does improve attention and thinking skills, but for many children, MPH does not improve these problems completely. The second treatment is a computer program, called CogmedRM. When children do CogmedRM, they practice game-like exercises on the computer that are designed to help improve a thinking skill called "working memory." This type of memory is what we use when we have to remember a small amount of information in our minds while we do something with it. For example, we use working memory when we add or subtract numbers in our head. Children use working memory when they listen to a teacher and take notes on what she says or follow her instructions. In this study, we want to see if working memory skills will improve when children with NF1 complete CogmedRM. Because other studies have shown that both CogmedRM and MPH can change the way the brain uses dopamine, we also think that children who are taking MPH while they do the CogmedRM program will have better results than children who are not taking MPH.

We will invite children and teenagers with NF1 and working memory problems to complete one of two versions of the CogmedRM program. In both versions, participants in the study will practice game-like exercises designed to improve working memory skills. Completing the program involves practicing for about 30 minutes a day, 3 to 5 times per week until children finish 25 days of practice. In the first version, the CogmedRM exercises get harder and harder as children answer items correctly. In this way, the program "trains" working memory just like we can train muscles by lifting weights at the gym. In the other version, the exercises stay at the same level of difficulty for the whole program. If we compare how much the working memory skills improve after children in each group finish the program, we can see if CogmedRM is helpful. Some children with NF1 are already using MPH to help with attention and working memory difficulties, while others have never used MPH or have tried MPH without any benefit. So, to find out if children who are taking MPH have better results after finishing the CogmedRM program, we will also compare how much working memory improvement was made by children who were taking MPH while they did the program compared to those not taking any MPH.

The CogmedRM program has no known side effects, can be used along with any medication, costs less than traditional treatment with a therapist, and, importantly, can be completed at home by children as young as 4 years of age. If CogmedRM, either by itself or in combination with MPH, is shown to improve working memory in children and teenagers with NF1, this intervention plan could rapidly be used by others with NF1 around the country. This approach would allow a wide range of patients to be treated at an early age, before problems with thinking and learning can lead to difficulties at school, with friends, and at home. Prevention of long-term difficulties could then become a real option for patients with NF1 and thinking or learning problems.