Overview

This trial is active, not recruiting.

Condition social anxiety in autistic adults
Treatments placebo, mdma
Phase phase 2
Sponsor Multidisciplinary Association for Psychedelic Studies
Collaborator Los Angeles Biomedical Research Institute
Start date February 2014
End date December 2016
Trial size 12 participants
Trial identifier NCT02008396, MAA-1

Summary

This randomized, double-blind study is intended to test the safety and feasibility of using 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy, compared with placebo, to treat social anxiety in autistic adults. Subjects will be randomly (by chance) assigned to receive placebo or MDMA during two experimental sessions. The first six subjects in the study will be randomized to placebo (2) or 75 mg MDMA on the first session and 100 mg MDMA on the second session (4). The next six subjects will be randomized to placebo (2) or 100 mg MDMA on the first session and 125 mg MDMA on the second session (4). The study will explore whether two doses of MDMA, combined with selected therapeutic activities, can reduce social anxiety. The study takes place in Los Angeles, California and requires about 15 visits to the study location over several months. Study subjects will meet with the investigators three times to prepare for the MDMA sessions, and they will meet with them on three occasions and receive daily phone calls for safety monitoring for a week after each session. Blood samples will be collected at baseline, two hours after drug administration during the second experimental session, one month and six months after the second experimental session to measure amounts of the hormones oxytocin, arginine vasopressin and cortisol in plasma. Subjects will return six months after their second experimental session for measurements of and social anxiety and other symptoms and an interview. Subjects will learn what they received at this visit. Subjects who received placebo can go through treatment again to have two sessions with MDMA, the first with 75 mg and the second with 125mg MDMA. Social anxiety, anxiety, depression, stress, self-esteem, empathy, and quality of life will be measured before and after experimental sessions.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Placebo Comparator)
Subjects will receive inactive placebo in two sessions
placebo Inactive placebo
Subjects will receive capsules of lactose of identical appearance to MDMA capsules during each of two experimental sessions. Capsules will be administered along with therapeutic activities during experimental sessions .
(Experimental)
Participants will receive 75 to 125 mg during two sessions; first session dose lower than second session dose.
mdma 3,4-methylenedioxymethamphetamine, MDMA
Participants receive a capsule of 75 or 100 mg during the first of two experimental sessions and a capsule of 100 or 125 mg MDMA on the second of two experimental sessions. They will receive MDMA along with selected therapeutic activities during each experimental session.

Primary Outcomes

Measure
Change in Lieberman Social Anxiety Scale score
time frame: Baseline, one day post-drug, 2 weeks post-drug, one month post-drug, 6 month follow-up

Secondary Outcomes

Measure
Beck Depression Inventory (BDI)
time frame: Pre-drug, one day post-drug, 2 weeks post-drug, one month post-drug, monthly 1-5 months post-drug, 6 month follow-up
State Trait Anxiety Inventory (STAI)
time frame: Pre-drug, one day post-drug, 2 weeks post-drug, one month post-drug, monthly 1-5 months post-drug, 6 month follow-up
Perceived Stress Scale (PSS)
time frame: Pre-drug, one day post-drug, two weeks post-drug, one month post-drug, monthly by mail (1-5 months post drug), 6 month follow-up
Interpersonal Reactivity Index (IRI)
time frame: Pre-drug, one day post-drug, one month post-drug, 6 month follow-up
Rosenberg Self-Esteem Scale (RSES)
time frame: Pre-drug, one day post-drug, one month post-drug, monthly by mail (1-5 months post drug), 6 month follow-up
Columbia Suicide Severity Rating Scale (C-SSRS)
time frame: Baseline
Columbia Suicide Severity Rating Scale (C-SSRS)
time frame: Average (given every face to face visit from pre-drug to 6 month follow up)
The Awareness of Social Inference Test
time frame: Pre-drug, experimental session 1, experimental session 2, one month post-drug, 6 month follow-up
Quality of Life Questionnaire
time frame: Pre-drug, 6 month follow-up
Emotion Regulation Questionnaire
time frame: Pre-drug, one month after second drug session, 6-month follow-up
Toronto Alexithymia Scale (TAS-20)
time frame: Pre-drug, one month after second drug session, 6-month follow-up
Peak systolic blood pressure
time frame: Experimental session 1
Peak diastolic blood pressure (DBP)
time frame: Experimental session 1
Peak heart rate (HR)
time frame: Experimental session 1
Peak body temperature (BT)
time frame: Experimental session 1
Average systolic blood pressure
time frame: Experimental session 1
Average diastolic blood pressure (DBP)
time frame: Experimental session 1
Average heart rate (HR)
time frame: Experimental session 1
Average body temperature (BT)
time frame: Experimental session 1
Peak systolic blood pressure
time frame: Experimental session 2
Peak diastolic blood pressure (DBP)
time frame: Experimental session 2
Peak heart rate (HR)
time frame: Experimental session 2
Peak body temperature (BT)
time frame: Experimental session 2
Average systolic blood pressure
time frame: Experimental session 2
Average diastolic blood pressure (DBP)
time frame: Experimental session 2
Average heart rate (HR)
time frame: Experimental session 2
Average body temperature (BT)
time frame: Experimental session 2

Eligibility Criteria

Male or female participants at least 21 years old.

Inclusion Criteria: - Have a diagnosis of Autism Spectrum Disorder - Have at least moderate social anxiety (LSAS score =>60) - MDMA-naive (no past use of MDMA/ecstasy) - Are at least 21 years old - Have completed two years of college-level education or comparable vocational training - Willing to refrain from psychiatric medication for at least 5 half-lives plus a week prior to experimental session - Agree to follow all study-related instructions and restrictions, including restrictions on food, alcohol and caffeine consumption prior to experimental sessions - Willing to commit to preparatory sessions, medication management, experimental sessions, follow-up sessions and to complete evaluation instruments. - Agree not to use MDMA/ecstasy outside of study sessions during the study, including the follow up period - Willing to be contacted on a daily basis for a week after each experimental session - willing to provide a contact willing and able to be reached by investigators, accompany the subject during some or all of the study visits, and complete study measures - Willing to give blood samples - Are proficient in speaking and reading English. Subjects communicating with text-to-speech technology will also be permitted to enroll. Exclusion Criteria: - Upon review of medical or psychiatric history must not have any current or past diagnosis that would be considered a risk to participation in the study. - Are abusing illegal drugs; - Are not able to give adequate informed consent. - Are not able to attend face-to-face visits or those who plan to move out of the area within the treatment period. - Are pregnant or nursing, or if a woman who can have children, those who are not practicing an effective means of birth control;

Additional Information

Official title Placebo-controlled, Randomized, Blinded, Dose Finding Phase 2 Pilot Safety Study of MDMA-assisted Therapy for Social Anxiety in Autistic Adults
Principal investigator Charles S. Grob, MD
Description Studies suggest that autistic adults are at greater risk for social anxiety. Social anxiety is a condition characterized by fear of scrutiny and avoidance of social interactions. Social anxiety frequently compounds the considerable social challenges experienced by autistic adults. There are currently no FDA-approved pharmacologic treatments for autistic adults, although off-label prescription of selective serotonin reuptake inhibitors (SSRIs) are on the rise in this population. Based on the known effects of MDMA, as well as individual reports from autistic adults, this exploratory study will focus on enhancing functional skills in this underserved population, who tend to experience greater anxiety, depression and victimization than typically developing adults. The main objective of this study is to collect safety data to examine whether MDMA-assisted therapy will be tolerated and to estimate effect size of symptom reduction in social anxiety and other psychiatric symptoms that are common in the adult autistic population as evaluated by standard clinical measures. The primary outcome measure will be change in social anxiety levels as measured by the Lieberman Social Anxiety Scale (LSAS). Secondary measures include those of social anxiety, anxiety, depression, stress, self-esteem, emotion labeling and recognition, empathy, and quality of life, and blood levels of the hormones oxytocin, arginine vasopressin and cortisol. Each of the 12 subjects will participate in two blinded experimental sessions, assisted by either MDMA or placebo lasting seven hours within a brief course of non-drug therapy. The non-drug therapy includes three hour-long preparatory sessions at the start of the study and three hour-long integrative sessions during the month after each experimental session at two week intervals. This study is designed as a dose escalation study to assist with the exploration of safety and finding the most effective dose in this population. Subjects assigned to the MDMA group will receive two of three different doses, either 75mg, 100mg, or 125 mg MDMA. Overall, eight subjects (66.7%) will be randomized to the MDMA group and four subjects (33.3%) will be randomized to the placebo group. During the study, there will be a maximum of 24 experimental sessions with MDMA, with eight sessions in each dose group, and eight experimental sessions with placebo. Observations before, during, and after experimental sessions will be compared between these groups of equal size to explore the effects of MDMA-assisted therapy in the first double The Principal Investigator will evaluate all subjects to confirm autistic status. In addition, autistic status will be confirmed with the gold-standard diagnostic measure of autism in adults. Upon enrollment, subjects will meet with the study therapists for three 1-hour preparatory sessions scheduled within the month prior to the first experimental session to discuss what to expect during experimental sessions. In-person visits will occur in a private room at the research facility. All in-person sessions will be video recorded. Video recordings will be used for research and training purposes after the study. During experimental sessions, there will be periods of structured and unstructured interactions. The structured interactions will be selected based on elements of therapeutic interventions that are currently in use in this population for the treatment of social anxiety. An overnight stay at a hotel located close to the site will be offered to subjects, accompanied by their support partners, if they live further than 30 miles from the site on the night following the experimental session. Subjects will attend a 1-hour follow-up integrative therapy session on the day after the experimental session. Two additional integrative sessions will be conducted two weeks apart following each experimental session. During integrative sessions subjects will receive support in integrating their experiences and insights from the experimental session. The second experimental session will be scheduled approximately one month after the first experimental session, after outcome assessments have been completed. Biomarker levels will be analyzed to determine if MDMA-assisted therapy causes changes in these modulators of social behavior in this population as previously demonstrated in typically developing adults. Biomarker levels will be analyzed for persisting effects at one month and 6 months after treatment. Blood samples will be obtained from all subjects to measure plasma OT, AVP and CORT, which will be used to explore as potential surrogate endpoints at baseline, two hours after drug administration during the second experimental session, one month after the second experimental session, and at 6-month follow-up. Social anxiety will be measured by interview with a blinded Independent Rater. Questionnaires measuring anxiety, depression, self-esteem, emotion labeling, emotion recognition, stress, and self-esteem will be given at baseline and throughout treatment. Quality of life will be assessed by interview at baseline and 6-month follow.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Multidisciplinary Association for Psychedelic Studies.