Proof of Mechanism Study for the Treatment of Social Anhedonia in ASD

NCT03243552 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: ACEPIV
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This project will use the experimental medicine approach of a Phase IIa Proof of Mechanism 16-week, randomized, double-blind, controlled trial of L-DOPA versus placebo administration in combination with a 16 week social skills training group in order to: 1) identify differences in social reward processes in adolescent and young adult ASD participants versus healthy controls as measured by fMRI activation in reward circuitry; 2) provide evidence of dopaminergic moderating effects on social reward components in ASD with greater pre- to post-treatment changes expected in the subjects randomized to L-DOPA versus placebo; 3) examine the hypothesis that baseline readouts of putative dopamine signaling (wanting activation responses) will predict the extent of fMRI reward-related activation changes pre- to post-treatment; and, 4) examine the proposed relationship between pre- to post- L-DOPA fMRI reward changes and changes in individual self-report ratings of social wanting and ratings of videotaped positive affect in a structured interaction with an examiner. The study will enroll 56 participants with DSM-5 ASD between the ages of 13-30 years of age and 18 healthy control participants without histories of psychopathology for baseline comparisons.

Conditions

ASD

Outcome Measures

Primary Outcomes (1)

• Change in fMRI: Social Reward Task from Baseline to week 16 (4 months)

  BOLD Activation: VS, ACC, OFC, Amygdala, Hippocampus (same units of measure)

  Baseline, week 16

Secondary Outcomes (8)

• Change on Anticipatory and Consummatory Interpersonal Pleasure Scale Adolescent (ACIPS-A)

  Baseline, week 8 (midpoint), week 16 (4 month/end of study)

• Change on Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS)

  Baseline, week 8 (midpoint), week 16 (4 month/end of study)

• Change on Child Behavior Checklist (CBCL)

  Baseline, week 16 (4 month/end of study)

• Change on Youth Self Report (YSR)

  Baseline, week 16 (4 month/end of study)

• Change on Adult Behavior Checklist (ABCL)

  Baseline, week 16 (4 month/end of study)

Study Arms (2)

L-DOPA versus Placebo

ACTIVE COMPARATOR

L-DOPA or placebo (1:1 randomization). Dosing will begin at 25mg carbidopa/100mg L-DOPA in 3 divided doses, with a fixed-flexible titration schedule, allowing dose increases once per week of 100mg L-DOPA. Maximum dose is 600mg/d.

Drug: L-DOPA versus Placebo; Behavioral: Social Skills Training

Social Skills

EXPERIMENTAL

All participants will receive 16-week manualized social skills training.

Drug: L-DOPA versus Placebo; Behavioral: Social Skills Training

Interventions

L-DOPA versus Placebo DRUG

Participants will be randomized in a blocked schedule to yield 1:1 L-DOPA: placebo assignment.

L-DOPA versus Placebo; Social Skills

Social Skills Training BEHAVIORAL

ASD participants will be enrolled concurrently in a 16-week manualized, structured, group-based, social skills training program (PEERS).

Also known as: PEERS

L-DOPA versus Placebo; Social Skills

Eligibility Criteria

• Age: 13 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• ages 13 - 30 years inclusive;
• meets diagnostic criteria for ASD by clinical evaluation and ADOS;
• estimated FS IQ \>70; 4) English reading ability of 6th grade;
• ability to participate and complete protocol expectations (fMRI scan, testing) in the examining clinician's judgment; and
• planned enrollment and acceptance for the UCLA PEERS® adolescent or young adult social skills training program.

You may not qualify if:

• significant perceptual deficits;
• need for continuation or anticipated of use of prohibited dopamine-modifying medications (stimulants, antipsychotics);
• presence of serious behavioral comorbidity such as aggression, major depressive disorder requiring additional intervention, or self-injurious behavior, or current of past history of suspected psychotic disorder;
• history of tic disorder;
• presence of significant medical illness which may impact CNS function.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Study Officials

• James T McCracken, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Phase IIa Proof of Mechanism 16-week, randomized, double-blind, controlled trial of L-DOPA versus placebo.

Study Record Dates

• First Submitted: July 27, 2017
• First Posted: August 9, 2017
• Study Start: June 1, 2017
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: June 28, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)