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Impact of Combined Medication and Behavioral Treatment for ASD & ADHD

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ClinicalTrials.gov Identifier: NCT03242772
Recruitment Status : Recruiting
First Posted : August 8, 2017
Last Update Posted : December 18, 2018
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. 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 prior to initiating early behavioral intervention, and (2) identify changes in behavioral and neurophysiological activity that may underlie improved outcomes in children with comorbid ASD and ADHD. The primary aim of this study is to evaluate whether a stimulant treatment augments efficacy of a novel, parent-delivered, behavioral intervention based on the Early Start Denver model (P-ESDM). 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 1 year long (52- 60 weeks). Eligible participants will be randomly assigned to the active medication or placebo, which will be administered over the course of 24 weeks (weeks 0-24). The behavioral intervention with coaching will be provided for 12 weeks (weeks 10-22) to all participants. Between weeks 24 to 52 participants will continue behavior intervention without coaching and will be given the option to pursue ADHD medication outside of the research study.

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

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 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 : May 30, 2018
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: P-ESDM + Amphetamine

Amphetamine regimen (24 weeks total duration) will begin 10 weeks prior to initiation of Parent-Delivered Early Start Denver model (P-ESDM), continue throughout 12 weeks of P-ESDM, and 2 weeks after P-ESDM. The drug is an orally dissolvable, extended-release form of d- and l-amphetamine.

Both arms will receive 12 consecutive weekly P-ESDM sessions (1 hr each)

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 by 1 tablet = 3.1 mg or 0 mg every 2 weeks unless there are intolerable adverse effects or great improvement in ADHD symptoms to a target dose of 4 tablets = 12.4 mg or 0 mg of Adzenys- XR-ODT. The allowable dose range will range from 1.6/0 mg (1/2 tablet) to 18.6/0 mg (6 tablets). Doses may be reduced at any point during the trial (typically in 1 tablet increments) but only may be increased every two weeks in order to fully assess potential benefits and adverse events of the current dose.
Other Name: Adzenys XR-ODT

Behavioral: P-ESDM
Weekly sessions of the behavioral intervention will be delivered by a certified P-ESDM therapist. All participants in the trial and their primary caregivers will receive coaching following a manualized intervention (includes individualized learning objectives, intervention coaching for behavior management, handouts).
Other Names:
  • Early Start Denver Model
  • Parent-Delivered Early Start Denver Model

Placebo Comparator: P-ESDM + Placebo Oral Tablet

Placebo regimen (24 weeks total duration) will begin 10 weeks prior to initiation of Parent-Delivered Early Start Denver model (P-ESDM) and continue throughout 12 weeks of P-ESDM. The placebo contains no active drug and appears identical to the amphetamine (active drug).

Both arms will receive 12 consecutive weekly P-ESDM sessions (1 hr each)

Behavioral: P-ESDM
Weekly sessions of the behavioral intervention will be delivered by a certified P-ESDM therapist. All participants in the trial and their primary caregivers will receive coaching following a manualized intervention (includes individualized learning objectives, intervention coaching for behavior management, handouts).
Other Names:
  • Early Start Denver Model
  • Parent-Delivered Early Start Denver Model

Drug: Placebo Oral Tablet
Matched placebo tablets will be administered in the morning and provided for 24 weeks (starting 10 weeks prior to initiation of P-ESDM Intervention). Placebo appears identical to the active drug (Adzenys-XR-ODT) and flexible titration schedule will also be used.




Primary Outcome Measures :
  1. Change in Adaptive Behavior [ Time Frame: Weeks 0, 10, 24, and 52 ]
    The primary outcome measure is change in the mean of the interview version of the VABS-3 socialization subscale and communication subscale standard scores. These standardized scores have real clinical significance, account for the variable rates of change observed developmentally, and reflect the core symptom domain targeted by P-ESDM: social communication.


Secondary Outcome Measures :
  1. Change in Sustained Attention [ Time Frame: Weeks 0, 10, 24 (week 0 = baseline) ]
    A naturalistic parent-child interaction task (PCIT) (DeVito et al. 2016) will be administered to assess sustained attention. Children and their parents are observed during a series of tasks that include play interactions with developmentally appropriate toys. Tasks are video recorded and children are reliably coded using a behavioral coding scheme by raters naïve to diagnostic status in terms of each of several engagement states: unengaged, onlooking, object-focused, person-focused, supported joint attention, and coordinated joint attention.

  2. Change in ADHD symptoms [ Time Frame: Weeks 0, 2, 6,10,16, 24, 52 (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 52).

    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

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Ages Eligible for Study:   36 Months to 84 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 96 months.
  4. Children who are 73 months to < 96 months must also have a receptive language developmental age of = or < than 72 months to ensure that child's abilities are in the appropriate range for P-ESDM.
  5. 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), the Standardized ADHD Diagnostic Interview for Preschoolers and the parent completed ADHD-RS.
  6. In good general health as evidenced by medical history, physical exam and review of safety labs and electrocardiogram.

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 P-ESDM or completion of key assessments (see MOP for details).
  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 P-ESDM coaching as deemed by the PI or clinician.
  8. Significant change in the type or intensity of behavioral interventions received by the child during the 8 weeks prior to Week 0.
  9. Presence of more than one psychiatric condition in addition to ASD and ADHD confirmed with a semi-structured psychiatric interview and expert consensus diagnosis. See MOP for procedures for senior clinician review of psychiatric conditions other than oppositional defiant disorder, dysthymic mood dysregulation disorder, or anxiety conditions.
  10. Study clinician judgment that it is not in the best interests of the participant and/or the study for the child to participate.
  11. 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)
  12. 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).
  13. History of neonatal brain damage. (eg., with diagnoses hypoxic or ischemic event)
  14. Any known environmental circumstances that is likely to account for the picture of autism in the proband (severe nutritional or psychological deprivation etc.)

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
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Contact: Geraldine Dawson, PhD (919) 684-3165 geraldine.dawson@dm.duke.edu

Locations
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United States, North Carolina
Duke Center for Autism and Brain Development Recruiting
Durham, North Carolina, United States, 27705
Contact: Geraldine Dawson         
Sponsors and Collaborators
Duke University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT03242772     History of Changes
Other Study ID Numbers: Pro00085179
1P50HD093074-01 ( U.S. NIH Grant/Contract )
First Posted: August 8, 2017    Key Record Dates
Last Update Posted: December 18, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Disease
Attention Deficit Disorder with Hyperactivity
Autism Spectrum Disorder
Pathologic Processes
Attention Deficit and Disruptive Behavior Disorders
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