Evaluating Assessment and Medication Treatment of ADHD in Children With Down Syndrome

Children with Down syndrome (DS) have a 3-5 time greater prevalence of Attention Deficit Hyperactivity Disorder (ADHD) than typically developing (TD) children. Despite this higher risk of ADHD, rates of stimulant medication treatment are disproportionately low in children with DS+ADHD, even though stimulants are the most efficacious ADHD treatment and are recommended by consensus guidelines for use in children with intellectual disability and ADHD.

Therefore, the investigators propose a pilot clinical trial to support the first randomized clinical trial of stimulant medication in children with DS+ADHD. The purpose of this study is to inform sample size estimates for the larger clinical trial. All children enrolled in the study will complete a comprehensive assessment battery evaluating ADHD diagnostic criteria as well as behavioral, cognitive, academic, and functional impairments. Further, children will take part in the pilot methylphenidate clinical trial to inform measures retained and desired sample size for the future clinical trial.

The purpose of this study is to conduct a small pilot clinical trial of stimulant medication treatment (i.e., methylphenidate (MPH)) in children with DS+ADHD to inform sample size estimates and power calculations for a larger clinical trial. In sum, this study will directly address issue related to under-utilization of stimulant treatment in children with DS+ADHD, and it has the potential to significantly improve the outcomes of approximately 45,000 children with DS+ADHD nationwide.

To achieve this, 30 children with DS+ADHD, between the ages of 6.00-17.99 years, will be invited to participate in a pilot clinical trial across two sites. Following pre-screening to determine study eligibility, children with DS+ADHD will be assessed at 14 different times points. The first pre-medication visit will include baseline intelligence, diagnostic, behavioral, cognitive, health, and functioning assessments. The second through sixth visits will begin Phase 1 of the pilot clinical trial, and during this time, participants will begin the lowest dose of MPH and titrate incrementally upward per pediatric guidelines based on the participant's height and weight. Weekly diagnostic and health assessments will be conducted to monitor the safety and efficacy of MPH during this phase. Further, this weekly monitoring will ultimately guide the selection of the participant's optimal dose. At the seventh visit, participants will enter Phase 2 of the pilot clinical trial where they will be randomized to receive an optimal dose of MPH (as determined by the assessments conducted throughout the titration phase) or the placebo. This visit will involve a repeat of most of the baseline measures. The eighth visit will initiate Phase 3 of the pilot clinical trial in which participants will crossover to the study intervention not previously assigned during Phase 2. For example, a participant who was assigned his or her optimal dose during Phase 2 will receive the placebo during Phase 3, and vice versa. Further, this visit will involve a repeat of the assessments conducted during Phase 2 which allows each participants to serve as his or her own control, contributing data both while on an optimal dose of MPH and while on the placebo.

Prior to commencing Phase 4, MPH non-responders or placebo responders will be removed from the study and referred for non-study (clinical) treatment. Participants for whom MPH is judged to be effective and tolerable based on clinician ratings and parent/teacher reports will be invited to undergo an open label trial with their optimal MPH dose for a six-month maintenance period. During this phase, participants will undergo monthly diagnostic and health assessments to monitor the safety and efficacy of his or her optimal dose of MPH. The final visit (week 31) will include diagnostic, behavioral, cognitive, functioning, and health assessments to evaluate change across time.