Pilot Study of Executive Function Intervention to Improve Neurodevelopmental Outcomes in Children with CHD

Doctor's Name: 
Jane W. Newburger, MD
Doctor's Name 2: 
David Bellinger, MD
Hospital/Institution: 
Boston Children's Hospital

Striking improvements in the survival of patients with critical congenital heart disease (CHD) have revealed that this population harbors a high prevalence of neurologic and developmental abnormalities. The identification and treatment of neurodevelopmental morbidity constitute a primary aim in medical care and represent a public health priority as the number of adults with CHD soars. Executive function impairments and attention deficit disorders are at the core of the neurodevelopmental phenotype associated with CHD after open-heart surgery. These impairments manifest as behavioral dysregulation and problems with attention, lower working memory, and difficulties with organization and planning, and are a core feature of Attention Deficit Hyperactivity disorder (ADHD). In the population with CHD, executive function impairments lead to widespread real-life repercussions including reduced psycho-social functioning, frequent use of early special education and developmental services, as well as to a reduced quality of life. The proposed pilot study aims to address, for the first time, a cutting-edge question regarding the potential prevention and/or treatment of these critical neurodevelopmental impairments in the care of children with complex CHD.

This is the first randomized controlled trial (RCT) to test the hypothesis that Cogmed intervention will improve neurodevelopmental and behavioral outcomes in children with critical CHD. Cogmed is the most widely used evidence-based neurocognitive intervention that specifically targets executive function via intensive structured computerized working memory training. In the proposed pilot study, we will include school-age children with critical CHD who underwent at least one open-heart surgery during their first year of life. Eligible children will be randomly assigned to either the Cogmed intervention group or to a control group who will receive the standard of care. All children will undergo comprehensive neurodevelopmental evaluations at three time points: baseline, immediate post-treatment, and 3 months after the cessation of the intervention.

Our specific aims are as follows: Aim 1: to evaluate the immediate efficacy of home-based Cogmed intervention for neurodevelopmental outcomes including executive function, social development and ADHD symptom reduction in children with CHD. We hypothesize that children who receive the Cogmed intervention, compared to controls receiving standard of care, will show greater improvement from baseline to immediate post-treatment assessment in measures of executive function, social development and ADHD symptoms. Aim 2: to assess the longer-term effects of the Cogmed intervention at 3-month follow-up. We hypothesize that significant gains in neurodevelopmental and behavioral outcomes will persist at 3 month follow-up (e.g., 3 months after cessation of intervention) for children who received Cogmed, compared to controls. Finally, Aim 3: to explore cognitive, medical and socio-demographic factors associated with changes in neurodevelopmental and behavioral immediate post-treatment and 3-month follow-up scores for children who received Cogmed intervention. We predict that baseline executive dysfunction and/or univentricular heart anatomies and/or low socio-economic status will be primarily associated with larger positive effects of Cogmed intervention at immediate post-treatment and at 3-month follow-up. Most study outcomes are continuous variables. The efficacy of adaptive Cogmed will be evaluated by calculating within- and between-groups effect sizes (baseline to immediate post-treatment, baseline to 3-month follow-up), with use of an Intent-to-Treat (ITT) analysis. Linear regression models will assess differences between intervention groups on continuous outcomes. Logistic regression models will examine differences in probability of categorical outcomes. Because we will be conducting multiple comparisons, we will interpret effects based not only on significance level but also on the magnitude of differences.

To date, we have achieved a more nuanced understanding of the long-term neurodevelopmental dysfunction that patients with CHD commonly face. We are at a point where moving forward with targeted treatment strategies is essential in order to provide optimal care for the growing population with CHD. A gap in knowledge about proactive prevention and/or treatment options remains the biggest multidisciplinary challenge. Our study offers a unique opportunity for an important collaboration between professionals who are directly involved in the care of children with CHD. The multidisciplinary approach that we propose will undoubtedly generate future hypotheses regarding brain plasticity and neurodevelopmental recovery possibilities in children with CHD. Finally, our pilot RCT is intended to provide crucial preliminary information to build upon for future larger-scale multicenter RCTs within existing pediatric cardiology networks.

Award Date 1: 
2015
Award Amount 1: 
$90,026
Award Date 2: 
2016
Award Amount 2: 
$90,026