NCT03242772

Impact of Combined Medication and Behavioral Treatment for ASD & ADHD

Impact of Combined Medication and Behavioral Treatment in Young Children With Comorbid ASD and ADHD

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Duke University · Academic / Other
• Sex: All
• Age: 36 Months – 131 Months
• Healthy volunteers: Not accepted

Summary

Children with comorbid autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) have significantly worse outcomes than those with either ASD alone or ADHD alone. Effective early treatments that account for ADHD symptoms have not been developed for young children with ASD+ADHD. The overarching goals of this randomized, placebo-controlled, phase 2, pilot study are to (1) evaluate a novel early intervention that pharmacologically addresses ADHD symptoms while providing an ASD-targeted behavioral intervention, and (2) identify changes in behavioral and neurophysiological activity that may underlie improved outcomes in children with comorbid ASD and ADHD ages 3-10 years. The primary aim of this study is to evaluate whether a stimulant treatment augments efficacy of an ASD specific form of parent child therapy based on the Early Start Denver Model called ESDM influenced Parent Coaching. Secondary aims are to determine the efficacy of combined intervention in improving ADHD symptoms and the efficacy, safety, and tolerability of Adzenys-XR-ODT in young children with ASD+ADHD. The study will also examine correlations between behavioral changes and state-of-the-art eye-gaze tracking (EGT) and electroencephalographic (EEG) biomarkers to elucidate key ways in which ADHD impacts attentional and neural functioning in ASD+ADHD, and to potentially identify new targets for intervention in children with ASD+ADHD. The study is about 8 months long and will involve screening, baseline assessment followed by 10- 11 weeks of study drug treatment (active or placebo) and 8 sessions of ESDM informed parent coaching beginning after 2 weeks of study drug treatment, primary endpoint assessments at \~11 weeks, AE follow-up by phone at \~week 13 and remote FU 24 weeks after baseline. Eligible participants will be randomly assigned to the active medication or placebo, Between weeks 11 to 24, it is expected that the parent will use the behavioral strategies they were coached in even though they will not receive parent coaching. Participants will be given the option to pursue ADHD medication outside of the research study after week 11 assessments.

Detailed description

This randomized, placebo-controlled, Phase 2, single site, pilot study will evaluate the developmental impact of combined medication and behavioral treatment (COMB) versus placebo and behavioral treatment (BEH) in children with comorbid ASD +ADHD, who are between 36 and \< 132 months of age. The active medication treatment will be an orally dissolvable, extended release amphetamine preparation (Adzenys-XR-ODT) administered from weeks 0-\~11 and carefully titrated to the optimal dose using an algorithm that considers adverse events and improvement in attention symptoms with a flexible dose range of 1.55mg - 18.6mg/day. The target dose is 12.4mg/day. A placebo, matched to the active medication, will be titrated and adjusted using the same algorithm in the BEH arm. The provided behavioral treatment will be eight \~ hour long parent child therapy sessions of ESDM influenced parent coaching. Approximately 48 participants will be randomly assigned to either the COMB or BEH treatment arms. To account for possible differences in attrition due to potential poor tolerability of Adzenys-XR-ODT, participants will be randomized in a 7 COMB to 6 BEH ratio. Treatment assignment will be provided by the Data Management and Analysis Core (DMAC)using computer generated algorithms. The primary analyses will compare changes in outcomes between weeks 0 and 11 weeks. Exploratory analyses will explore changes between weeks 0 and 24. The primary outcome measure is change in amount and quality of joint engagement between the child and the parent during a semi-structured, 6 minute parent child interaction task (PCIT), which reflects the core symptom domain targeted by P-ESDM: social communication. Our key secondary outcomes will be changes in 1) the mean of the interview version of the VABS-3 socialization subscale and communication subscale standard scores and 2) clinician ratings of ADHD symptoms using the preschool ADHD-RS. We will also assess the safety and tolerability of Adzenys-XR-ODT compared to placebo.

Conditions

• Autism Spectrum Disorder
• Attention Deficit Hyperactivity Disorder

Interventions

Type	Name	Description
DRUG	Amphetamine	Study drug will be administered in the morning. Treatment will be initiated at 1 tablet = 3.1 mg or 0 mg of mixed amphetamine. Doses will be flexibly titrated upward and may be decreased or stopped at any time.
BEHAVIORAL	ESDM informed parent coaching	All participants will receive 8 weekly parent child therapy sessions will be delivered by a therapist trained in parent coaching and ESDM principles and strategies and utilizing a therapy manual,(includes coaching for behavior management and handouts).
DRUG	Placebo Oral Tablet	Matched placebo tablets will be administered in the morning and provided for 11 weeks . The tablets will be titrated in the same way as the active drug and may be stopped at any time.

Timeline

• Start date: 2018-12-14
• Primary completion: 2020-12-28
• Completion: 2021-04-19
• First posted: 2017-08-08
• Last updated: 2022-03-22
• Results posted: 2022-03-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study