Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Impact of Combined Medication and Behavioral Treatment for ASD & ADHD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03242772
Recruitment Status : Recruiting
First Posted : August 8, 2017
Last Update Posted : February 10, 2020
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Duke University

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.

Condition or disease Intervention/treatment Phase
Autism Spectrum Disorder Attention Deficit Hyperactivity Disorder Drug: Amphetamine Behavioral: ESDM informed parent coaching Drug: Placebo Oral Tablet Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Impact of Combined Medication and Behavioral Treatment in Young Children With Comorbid ASD and ADHD
Actual Study Start Date : December 14, 2018
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2022


Arm Intervention/treatment
Active Comparator: ESDM informed parent coaching + Amphetamine
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
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.
Other Name: Adzenys XR-ODT

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).

Placebo Comparator: ESDM informed parent coaching + Placebo Oral Tablet
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
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.




Primary Outcome Measures :
  1. Change in amount and quality of joint engagement between the child and parent during a semi-structured 6 minute parent child interaction task [ Time Frame: Weeks 0, 11 ]
    Higher scores mean greater/higher quality engagement and lower scores represent less/poorer engagement.


Secondary Outcome Measures :
  1. Change in Mean Socialization and Communication Subscales Standard Scores of the Vineland Adaptive Behavior Scale - 3rd edition, Interview Version (VABS-3) [ Time Frame: Weeks 0, 11, 24 ]
    Mean of standard scores for VABS-3 (socialization subscale and communication subscales) assess how the participant actually has been functioning over the preceding month with regard to communication and social behaviors. The VABS-3 comprehensive form will be administered as a semi-structured interview by a trained and research reliable staff member. The standard score is based on the participant's age and is normed from a large sample of typically developing children. The standard score has a mean of 100 and a standard deviation of 15. Higher scores represent more adaptive functioning and lower scores represent less adaptive functioning.

  2. Change in ADHD Symptoms using Preschool or School age ADHD Rating Scale (ADHD-RS) [ Time Frame: Weeks 0, 2, 7,11, (week 0 = baseline) ]

    ADHD Rating Scale (ADHD-RS) will assess symptom frequency using data from clinician completed ADHD-RS and parent completed ADHD-RS (only parent-completed ADHD-RS is completed at week 24).

    ADHD-RS includes 18 items, each rated on a 4 point scale (0-3);Total Score is the sum of all responses (0-54). An Inattention subscale and Hyperactivity/Impulsivity subscale (each range 0-27) are calculated based on individual items assessing those symptoms. Higher values represent worse outcomes for the subscales and the total scale. Normative scores are available. Clinically significant scores in boy are 14 for inattention items and 17 for hyperactivity/impulsivity items. Clinically significant thresholds in girls are 12 and 14 respectively. A supportive exploratory analysis will examine change to a nonclinically significant score by week 24 (using clinician rating) and week 52 (using only parent ratings) . If subscales are used, they would be summed to compute the total score.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   36 Months to 131 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of a parent signed and dated informed consent form.
  2. Stated willingness to comply with all study procedures and availability for the duration of the study.
  3. Aged 36 months to less than 132 months.
  4. 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
  5. In good general health as evidenced by medical history and physical exam.

Exclusion Criteria:

  1. Recent use of prohibited psychoactive medication in close proximity of baseline (Study Visit 2, Day 0). See MOP for specific medications that are prohibited and washout procedures.) Use of a monoamine oxidase inhibitor is prohibited within 14 days of baseline.
  2. Known allergic reactions to amphetamines or components of Adzenys-XR-ODT.
  3. Known history of sudden non-ischemic cardiac death in a first or second degree family member (sibling, parent, aunt, uncle, cousin or grandparent).
  4. Personal history of significant cardiac abnormalities or disease, particularly rhythm abnormalities.
  5. Significant visual, auditory or motor impairments that would preclude participation in therapy or completion of key assessments.
  6. Inability of the caregiver participating in P-ESDM and responding to questionnaires to fluently speak English.
  7. 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.
  8. 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.
  9. 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)
  10. 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).
  11. History of neonatal brain damage. (eg., with diagnoses hypoxic or ischemic event)
  12. Any known environmental circumstances that is likely to account for the picture of autism in the proband (severe nutritional or psychological deprivation etc.)
  13. Study clinician judgment that it is not in the best interests of the participant and/or the study for the child to participate.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03242772


Contacts
Layout table for location contacts
Contact: Lori Reinhart-Mercer, RN (919) 668-2993 autismresearch@duke.edu
Contact: Marina Spanos, PhD 919 681 3834 marina.spanos@duke.edu

Locations
Layout table for location information
United States, North Carolina
Duke Center for Autism and Brain Development Recruiting
Durham, North Carolina, United States, 27705
Contact: Lori Reinhart-Mercer, RN    919-668-2993    autismresearch@duke.edu   
Contact: Marina Spanos, PhD    919 681 3834    Marina.spanos@duke.edu   
Sponsors and Collaborators
Duke University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Layout table for investigator information
Principal Investigator: Geraldine Dawson, PhD Duke
Principal Investigator: Linmarie Sikich, MD Duke
Principal Investigator: Scott Kollins, PhD Duke

Layout table for additonal information
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT03242772    
Other Study ID Numbers: Pro00085179
1P50HD093074-01 ( U.S. NIH Grant/Contract )
First Posted: August 8, 2017    Key Record Dates
Last Update Posted: February 10, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Through NDAR, core assessment and diagnostic data that is de-identified, including measures such as ADOS and Vineland.
Supporting Materials: 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
URL: https://nda.nih.gov

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Attention Deficit Disorder with Hyperactivity
Attention Deficit and Disruptive Behavior Disorders
Disease
Autism Spectrum Disorder
Pathologic Processes
Neurodevelopmental Disorders
Mental Disorders
Child Development Disorders, Pervasive
Amphetamine
Central Nervous System Stimulants
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Dopamine Uptake Inhibitors