Proof of Mechanism Study for the Treatment of Social Anhedonia in ASD
| Status: | Recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 13 - 30 |
| Updated: | 1/16/2019 |
| Start Date: | June 1, 2017 |
| End Date: | June 2022 |
| Contact: | Jenny T Cowen, PhD |
| Email: | jcowen@mednet.ucla.edu |
| Phone: | 310-825-6170 |
Proof of Mecahism Study for the Treatment of Social Anhedonia in ASD
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.
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.
Participants will comprise two groups: 1) 56 (male and female) adolescents and young adults
likely to meet inclusion/exclusion confirmed by study assessment who will be outpatients,
ages 13 to 30 years, inclusive; and 2) 18 (male and female) healthy adolescents and young
adults without any history of significant psychiatric disorders or treatment, who will be
ambulatory, and will reflect the racial, ethnic, and socio-economic composition of Los
Angeles, and will be recruited without regard to gender, race, or ethnic background.
Healthy control adolescents (and parents) and young adults who meet all inclusion and
exclusion criteria, will undergo a one-day 4-5 hour research evaluation of current
functioning and behavior, cognitive function, including intellectual testing, urine drug
screen, completion of questionnaires about possible psychological symptoms, perform brief
tests to measure reward response, and complete a research Magnetic Resonance Imaging scan.
Healthy control will not receive any interventions or medication.
All eligible ASD participants will be enrolled concurrently in a 16-week, structured,
group-based, social skills training program (PEERS®). After screening evaluations, eligible
subjects will undergo baseline MRI scanning and behavioral assessments (self- and
parent-report measures, videotaped interaction) and then randomized in a blocked schedule to
yield 1:1 L-DOPA: placebo assignment, before beginning weekly social skills training.
Medication administration will begin simultaneously with social skills training, and subjects
will be seen weekly for the 1st 8 weeks, then biweekly for the final 4 weeks for safety
assessments, dose titration, and compliance checks. During the 16-week study period, primary
behavioral assessments will be repeated at Week 8 and at end of study on Week 16. A second
MRI scan will be obtained within + 4 days of last social skills session. A follow-up safety
phone call to assess post-study condition will be performed 30 days after completion of
double-blind. The rich set of behavioral observations obtained across the 16 weeks will allow
the possible identification of early clinical efficacy changes associated with L-DOPA
administration, which could add further support for investigating this mechanism in future
studies. Results from the project should inform reseacher's understanding of determinants of
social dysfunction in ASD and may support further investigation of treatments modulating
central nervous system dopamine function as a therapeutic strategy to enhance social
functioning in ASD.
likely to meet inclusion/exclusion confirmed by study assessment who will be outpatients,
ages 13 to 30 years, inclusive; and 2) 18 (male and female) healthy adolescents and young
adults without any history of significant psychiatric disorders or treatment, who will be
ambulatory, and will reflect the racial, ethnic, and socio-economic composition of Los
Angeles, and will be recruited without regard to gender, race, or ethnic background.
Healthy control adolescents (and parents) and young adults who meet all inclusion and
exclusion criteria, will undergo a one-day 4-5 hour research evaluation of current
functioning and behavior, cognitive function, including intellectual testing, urine drug
screen, completion of questionnaires about possible psychological symptoms, perform brief
tests to measure reward response, and complete a research Magnetic Resonance Imaging scan.
Healthy control will not receive any interventions or medication.
All eligible ASD participants will be enrolled concurrently in a 16-week, structured,
group-based, social skills training program (PEERS®). After screening evaluations, eligible
subjects will undergo baseline MRI scanning and behavioral assessments (self- and
parent-report measures, videotaped interaction) and then randomized in a blocked schedule to
yield 1:1 L-DOPA: placebo assignment, before beginning weekly social skills training.
Medication administration will begin simultaneously with social skills training, and subjects
will be seen weekly for the 1st 8 weeks, then biweekly for the final 4 weeks for safety
assessments, dose titration, and compliance checks. During the 16-week study period, primary
behavioral assessments will be repeated at Week 8 and at end of study on Week 16. A second
MRI scan will be obtained within + 4 days of last social skills session. A follow-up safety
phone call to assess post-study condition will be performed 30 days after completion of
double-blind. The rich set of behavioral observations obtained across the 16 weeks will allow
the possible identification of early clinical efficacy changes associated with L-DOPA
administration, which could add further support for investigating this mechanism in future
studies. Results from the project should inform reseacher's understanding of determinants of
social dysfunction in ASD and may support further investigation of treatments modulating
central nervous system dopamine function as a therapeutic strategy to enhance social
functioning in ASD.
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
We found this trial at
1
site
Los Angeles, California 90095
310-825-4321
Principal Investigator: James McCracken, MD
University of California at Los Angeles The University of California, Los Angeles (UCLA) is an...
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