Impact of Combined Medication and Behavioral Treatment for ASD & ADHD

NCT03242772 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: Pro000851791P50HD093074-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Autism Spectrum Disorder; Attention Deficit Hyperactivity Disorder

Outcome Measures

Primary Outcomes (1)

• Change in Amount and Quality of Joint Engagement Between the Child and Parent During a Semi-structured 6 Minute Parent Child Interaction Task

  Child engagement states measured by the Joint Engagement Rating Inventory (JERI); our outcome contains four items (rated on a 7-point Likert scale) that characterize various aspects of engagement. Higher scores mean greater/higher quality engagement and lower scores represent less/poorer engagement. Total range of score is 4-28.

  Baseline (Week -1), Endpoint (Week 10)

Secondary Outcomes (3)

• Change in Mean Composite Score (Socialization and Communication Subscales Standard Scores) of the Vineland Adaptive Behavior Scale - 3rd Edition, Interview Version (VABS-3)

  Baseline (Week -1), Endpoint (Week 10)

• Change in ADHD Symptoms Using Preschool or School Age ADHD Rating Scale (ADHD-RS) Total Score

  Baseline (Week 0), Week 10

• Changes in Objective Measures of Social Attention and Social Engagement Using Eye Gaze Tracking

  Baseline (Week -1), Week 10

Study Arms (2)

ESDM informed parent coaching + Amphetamine

ACTIVE COMPARATOR

Amphetamine regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The drug is an orally dissolvable, extended-release form of d- and l-amphetamine.

Drug: Amphetamine; Behavioral: ESDM informed parent coaching

ESDM informed parent coaching + Placebo Oral Tablet

PLACEBO COMPARATOR

Placebo regimen (11 weeks total duration) will begin 2 weeks prior to initiation of ESDM informed parent coaching (8 weekly sessions) and continue through the week 11 endpoint assessment. The placebo contains no active drug and appears identical to the amphetamine (active drug).

Behavioral: ESDM informed parent coaching; Drug: Placebo Oral Tablet

Interventions

Amphetamine DRUG

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.

Also known as: Adzenys XR-ODT

ESDM informed parent coaching + Amphetamine

ESDM informed parent coaching BEHAVIORAL

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).

ESDM informed parent coaching + Amphetamine; ESDM informed parent coaching + Placebo Oral Tablet

Placebo Oral Tablet DRUG

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.

ESDM informed parent coaching + Placebo Oral Tablet

Eligibility Criteria

• Age: 36 Months - 131 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Provision of a parent signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Aged 36 months to less than 132 months.
• Diagnosed with both ASD and ADHD based consensus diagnosis informed by results of the Autism Diagnostic Observation Schedule 2nd edition (ADOS-2), Autism Diagnostic Interview - Revised (ADI-R), and a Standardized ADHD Diagnostic Interview and the MINI psychiatric diagnostic interview.
• In good general health as evidenced by medical history and physical exam and review of safety labs and electrocardiogram.

You may not qualify if:

• Recent use of prohibited psychoactive medication in close proximity of baseline assessments. See MOP for specific medications that are prohibited and washout procedures. Use of a monoamine oxidase inhibitor is prohibited within 14 days of baseline.
• Known allergic reactions to amphetamines or components of Adzenys-XR-ODT.
• Known history of sudden non-ischemic cardiac death in a first or second degree family member (sibling, parent, aunt, uncle, cousin or grandparent).
• Personal history of significant cardiac abnormalities or disease, particularly rhythm abnormalities.
• Significant visual, auditory or motor impairments that would preclude participation in ESDM-informed parent coaching or completion of key assessments.
• Inability of the caregiver participating in P-ESDM and responding to questionnaires to fluently speak English.
• Parent's participation in another parent coaching intervention on more than a monthly basis that may affect study provided therapy as determined by the PI or clinician.
• Presence of any psychiatric conditions or psychiatric symptoms in addition to ASD and ADHD that would confound assessments and/or affect participation in the study as deemed by the PI or clinician.
• Known genetic (e.g. Fragile X) or neurological syndrome or condition with established link to autism, but not events in which the link to ASD is less well known/established (e.g., 16p11.2 CNVs, CHD8 mutations, Trisomy 21, 22q deletion syndrome)
• History of epilepsy or seizure disorder (except for history of simple febrile seizures or if the child is seizure free (regardless of seizure type) for the past year).
• History of neonatal brain damage. (eg., with diagnoses hypoxic or ischemic event)
• Any known environmental circumstances that is likely to account for the picture of autism in the proband (severe nutritional or psychological deprivation etc.)
• Study clinician judgment that it is not in the best interests of the participant and/or the study for the child to participate.

Sponsors & Collaborators

• Duke University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Duke Center for Autism and Brain Development

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity

Interventions

Amphetamine

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Attention Deficit and Disruptive Behavior Disorders

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Dr. Geraldine Dawson, PhD, PI of Duke Autism Center of Excellence
• Organization: Duke Center for Autism and Brain Development

geraldine.dawson@duke.edu

919-668-0070

Study Officials

• Geraldine Dawson, PhD

  Duke

  PRINCIPAL INVESTIGATOR

• Linmarie Sikich, MD

  Duke

  PRINCIPAL INVESTIGATOR

• Scott Kollins, PhD

  Duke

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2017
• First Posted: August 8, 2017
• Study Start: December 14, 2018
• Primary Completion: December 28, 2020
• Study Completion: April 19, 2021
• Last Updated: March 22, 2022
• Results First Posted: March 9, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 1 year after publication of the results for each of the specific aims or 3 years after the statistical analyses are completed
• Access Criteria: determined by committee of researchers/administrator at NDAR

Locations

US (1)