The investigators are conducting a 10-week brain imaging and medication study. They are doing the research to study the response of Attention-Deficit/ Hyperactivity Disorder (ADHD) in youth with Autism Spectrum Disorder (ASD) on extended-release formulation of mixed amphetamine salts (MAS) (also know as Adderall XR). The investigators also want to find out if taking MAS has any effect on the brains of children and adolescents with ADHD and ASD. This study will help researchers better understand how the use of MAS to treat ADHD effects children and adolescents with ASD. The investigators will compare MAS to a placebo. The placebo will look exactly like the MAS capsules but will contain no MAS. During this study, participants may get a placebo instead of MAS. Placebos are used in research studies to see if the study results are due to the study drug or due to other reasons. Participants with ASD and ADHD will complete 4-weeks of treatment with the study medication or placebo. They will complete bi-weekly study visits virtually via a telemedicine platform with the study doctor and complete questionnaires. On alternating weeks, they will meet with a Massachusetts General Hospital (MGH) study team member to discuss medication adherence and potential side effects. Participants will have the option to attend all study visits in-person if participants prefer. They will also complete baseline and endpoint Magnetic Resonance (MR) scan visits at Massachusetts Institute of Technology (MIT). During the MR Scan visits, they will complete a series of tasks to measure inattention, impulsivity, reward sensitivity, decision-making, and working memory. Participants without ADHD or ASD will complete eligibility screening with MGH. If eligible, they will be invited to baseline and endpoint MR scan visits at MIT. During the MR Scan visits, they will complete a series of tasks to measure inattention, impulsivity, reward sensitivity, decision-making, and working memory.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
196
Capsule
Capsule
Massachusetts General Hospital
Boston, Massachusetts, United States
Change in the clinician-rated ADHD-Rating Scale (ADHD-RS)
Efficacy will be assessed by reduction in ADHD symptoms as measured by change from baseline on the clinician-rated ADHD-Rating Scale (ADHD-RS). The ADHD-RS-V is a physician-rated scale to assess the ADHD symptom severity in participants aged 5 to 17 years old. It is an 18-item rating-scale corresponding to DSM-5 diagnostic symptom criteria. Total scores range from 0-54, where higher scores indicate greater severity. The outcome reported reflects the change from baseline in ADHD-RS score and negative scores represent improvement.
Time frame: Baseline to Week 4 (study endpoint)
Treatment Responder
Responders are defined as ≥30% reduction in clinician-rated ADHD-Rating Scale (ADHD-RS) and clinician-rated Clinical Global Impression-Improvement score for ADHD (ADHD-CGI-I) ≤2 OR ≥25% reduction in parent-rated ADHD-RS and clinician-rated ADHD-CGI-I score ≤2.
Time frame: Week 4 (study endpoint)
Pre and post treatment changes in ASD core symptoms on Social Responsiveness Scale 2 (SRS-2)
Change in ASD symptoms as measured by change from baseline on the Social Responsiveness Scale 2 (SRS-2) scale. The SRS-2 is a 65-item rating scale that is used to measure the severity of autism spectrum symptoms as they occur in natural settings. The SRS-2 School Age form is completed by a parent or guardian for patients ages 9-17. Total raw scores range from 0 to 195, with higher scores indicating increased symptom severity. The outcome reported reflects the change from baseline in SRS Total raw score and negative scores represent improvement.
Time frame: Baseline to Week 4 (study endpoint)
Pre and post treatment changes in brain functioning
The study's primary neuroimaging measures include pre and post-treatment changes in brain functioning using multiple neuroimaging modalities, including resting-state functional MRI to assess connectivity in key networks (default mode, salience, and frontoparietal), task-based fMRI during response inhibition tasks to evaluate activation in inhibitory control regions, and magnetic resonance spectroscopy to analyze neurometabolite concentrations. Multimodal neuroimaging techniques will help identify neural correlates of treatment response by examining changes in large-scale network connectivity patterns (default mode, salience, and frontoparietal), task-related activation in regions previously associated with attention and inhibition (right inferior frontal gyrus, subthalamic nucleus, and anterior cingulate cortex), and alterations in brain neurochemistry (glutamate, GABA, glutathione, N-acetyl aspartate).
Time frame: Baseline to Week 4 (study endpoint)
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