Impact of Combined Medication and Behavioral Treatment for ASD & ADHD
Condition: Autism Spectrum Disorder; Attention Deficit Hyperactivity Disorder
MeSH terms: Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder
Intervention: Amphetamine; ESDM informed parent coaching; Placebo Oral Tablet
Intervention description: 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.; 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).; 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.
Intervention MeSH terms: Amphetamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 18.0
Sex: All
Minimum age: 36 Months
Maximum age: 131 Months
Healthy volunteers: No

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.
    

Eligibility 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 and review of
             safety labs and electrocardiogram.

        Exclusion Criteria:

          1. 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.

          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
             ESDM-informed parent coaching 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.