Phase 2 Pilot Safety Study of MDMA-assisted Therapy for Social Anxiety in Autistic Adults

• ClinicalTrials.gov Identifier: NCT02008396
• Recruitment Status: Completed
• First Posted: December 11, 2013
• Results First Posted: October 14, 2020
• Last Update Posted: November 3, 2020
• Sponsor: Multidisciplinary Association for Psychedelic Studies
• Collaborator: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Information provided by (Responsible Party): Multidisciplinary Association for Psychedelic Studies

Tracking Information

• First Submitted Date: December 6, 2013
• First Posted Date: December 11, 2013
• Results First Submitted Date: September 18, 2020
• Results First Posted Date: October 14, 2020
• Last Update Posted Date: November 3, 2020
• Study Start Date: February 2014
• Actual Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 14, 2020)

• Liebowitz Social Anxiety Scale (LSAS) Total Score at Baseline [ Time Frame: Baseline ]
  The LSAS is a 24-item, semi-structured interview on the severity of Social Anxiety Disorder. The LSAS separately assesses fear and avoidance of 24 social situations. The scale is divided into 2 subscales, 13 situations concerning performance anxiety, and 11 situations pertaining to social situations. The 24 items are first rated on a Likert Scale from 0 to 3 on fear felt during the situations, and then the same items are rated regarding avoidance of the situation. Combining the total scores for the Fear and Avoidance sections provides an overall score with a maximum of 144 points and a minimum of 0 points. The higher the score, the greater the anxiety symptoms. The overall scores are interpreted as: 55-65 is moderate, 65-80 is marked, 80-95 is severe, and greater than 95 is very severe social anxiety symptoms.
• Liebowitz Social Anxiety Scale (LSAS) Total Score 1-Month Post Experimental Session 2 [ Time Frame: 1-Month Post Experimental Session 2 ]
  The LSAS is a 24-item, semi-structured interview on the severity of Social Anxiety Disorder. The LSAS separately assesses fear and avoidance of 24 social situations. The scale is divided into 2 subscales, 13 situations concerning performance anxiety, and 11 situations pertaining to social situations. The 24 items are first rated on a Likert Scale from 0 to 3 on fear felt during the situations, and then the same items are rated regarding avoidance of the situation. Combining the total scores for the Fear and Avoidance sections provides an overall score with a maximum of 144 points and a minimum of 0 points. The higher the score, the greater the anxiety symptoms. The overall scores are interpreted as: 55-65 is moderate, 65-80 is marked, 80-95 is severe, and greater than 95 is very severe social anxiety symptoms.
• Change in Leibowitz Social Anxiety Scale (LSAS) Total Score From Baseline to 1-Month Post Experimental Session 2 [ Time Frame: Baseline to 1-Month Post Experimental Session 2 ]
  The LSAS is a 24-item, semi-structured interview on the severity of Social Anxiety Disorder. The LSAS separately assesses fear and avoidance of 24 social situations. The scale is divided into 2 subscales, 13 situations concerning performance anxiety, and 11 situations pertaining to social situations. The 24 items are first rated on a Likert Scale from 0 to 3 on fear felt during the situations, and then the same items are rated regarding avoidance of the situation. Combining the total scores for the Fear and Avoidance sections provides an overall score with a maximum of 144 points and a minimum of 0 points. The higher the score, the greater the anxiety symptoms. The overall scores are interpreted as: 55-65 is moderate, 65-80 is marked, 80-95 is severe, and greater than 95 is very severe social anxiety symptoms.

Original Primary Outcome Measures (submitted: December 6, 2013)

Change in Lieberman Social Anxiety Scale score [ Time Frame: Baseline, one day post-drug, 2 weeks post-drug, one month post-drug, 6 months post-drug ]

Semi-structured interview assessing social anxiety symtoms

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: December 6, 2013)

• Blood oxytocin levels [ Time Frame: Baseline, 2 h post-drug, 2 weeks post-drug, one month post-drug, 6 months post-drug ]
  Measures level of oxytocin released after MDMA or placebo
• Blood arginine vasopressin (AVP) levels [ Time Frame: Baseline, 2 h post-drug, 2 weeks post-drug, one month, post-drug, 6 months post-drug ]
  Measures level of oxytocin released after MDMA or placebo
• Blood cortisol levels [ Time Frame: Baseline, 2 h post-drug, 2 weeks post-drug, one month post-drug, 6 months post-drug ]
  Measures level of oxytocin released after MDMA or placebo

Descriptive Information

• Brief Title: Phase 2 Pilot Safety Study of MDMA-assisted Therapy for Social Anxiety in Autistic Adults
• Official Title: A Placebo-controlled, Randomized, Blinded, Dose Finding Phase 2 Pilot Safety Study of MDMA-assisted Therapy for Social Anxiety in Autistic Adults

Brief Summary

This double-blind, randomized, placebo-controlled exploratory pilot study assessed the safety and feasibility of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for social anxiety in MDMA-naïve adults on the autism spectrum. Each of the 12 subjects participated in two blinded experimental sessions, assisted by either MDMA (75 mg to 125 mg) or placebo, which lasted seven hours. Before experimental sessions, participants underwent three separate hour-long preparatory sessions to learn what to expect and complete pre-treatment assignments. After each experimental session, participants underwent three separate hour-long integrative sessions to help integrate their experiences and insights from the experimental sessions.

Subjects assigned to the MDMA group received two of three different doses, either 75 mg, 100 mg, or 125 mg MDMA. Overall, eight subjects were randomized to the MDMA group and four subjects were randomized to the placebo group. Observations before, during, and after experimental sessions were compared between these groups.

The main objective of this study was to collect safety data to examine whether MDMA-assisted therapy was tolerated and to estimate symptom reduction in social anxiety and other psychiatric symptoms. The primary outcome measure was change in social anxiety symptoms as measured by the Liebowitz Social Anxiety Scale (LSAS) [Heimberg et al., 1999].

Detailed 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 focused on enhancing functional skills in this underserved population, who tend to experience greater anxiety, depression and victimization than typically developing adults. This double-blind, randomized, placebo-controlled exploratory pilot study assessed the safety and feasibility of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for social anxiety in MDMA-naïve adults on the autism spectrum.

The main objective of this study was to collect safety data to examine whether MDMA-assisted therapy was tolerated and to estimate 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 was change in social anxiety symptoms as measured by the Liebowitz Social Anxiety Scale (LSAS) [Heimberg et al., 1999].

Each of the 12 subjects participated in two blinded experimental sessions, assisted by either MDMA or placebo, which lasted seven hours. Before experimental sessions, participants underwent three separate hour-long preparatory sessions to learn what to expect and complete pre-treatment assignments. After each experimental session, participants underwent three separate hour-long integrative sessions to help integrate their experiences and insights from the experimental sessions.

This study was designed as a dose escalation study to assist with the exploration of safety and finding the most effective dose in this population. Upon enrollment, the first six subjects (Group 1) was randomized to receive one dose of either placebo (N=2) or 75 mg of MDMA (N=4). In the second experimental session one month later, Group 1 subjects randomized to MDMA escalated to 100 mg of MDMA, unless contraindicated. The second six subjects enrolled (Group 2) were randomized to receive one dose of either placebo (N=2) or 100 mg of MDMA (N=4). In the second experimental session one month later, Group 2 subjects randomized to MDMA escalated to 125 mg of MDMA, unless contraindicated.

The blind was maintained through the six-month follow-up. In Stage 2 after the blind was broken, subjects who received placebo in Stage 1 were offered an open-label extension with two experimental sessions of MDMA scheduled one month apart. Subjects received 75 mg of MDMA in the first session and escalated to 125 mg of MDMA in the second session, unless contraindicated.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Social Anxiety in Autistic Adults

Intervention

• Drug: 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 psychotherapy.
  Other Name: Inactive placebo
• Drug: 75 mg to 125 mg 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 during the second experimental session. They will receive MDMA with psychotherapy.
  Other Name: 3,4-methylenedioxymethamphetamine, MDMA
• Behavioral: Psychotherapy
  Psychotherapy conducted throughout experimental sessions. Therapists will use a largely nondirective approach. 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.
  Other Name: Manualized MDMA-assisted psychotherapy

Study Arms

• Placebo Comparator: Inactive Placebo with Psychotherapy
  Subjects will receive inactive placebo during two psychotherapy sessions lasting approximately 7 hours.
  Interventions:

  • Drug: Placebo
  • Behavioral: Psychotherapy
• Experimental: 75 mg to 125 mg MDMA with Psychotherapy
  Participants will receive 75 to 125 mg during two psychotherapy sessions lasting approximately 7 hours; first session dose lower than second session dose.
  Interventions:

  • Drug: 75 mg to 125 mg MDMA
  • Behavioral: Psychotherapy

Publications *

• Heimberg RG, Horner KJ, Juster HR, Safren SA, Brown EJ, Schneier FR, Liebowitz MR. Psychometric properties of the Liebowitz Social Anxiety Scale. Psychol Med. 1999 Jan;29(1):199-212.
• Danforth AL, Grob CS, Struble C, Feduccia AA, Walker N, Jerome L, Yazar-Klosinski B, Emerson A. Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Psychopharmacology (Berl). 2018 Nov;235(11):3137-3148. doi: 10.1007/s00213-018-5010-9. Epub 2018 Sep 8.
• Danforth AL, Struble CM, Yazar-Klosinski B, Grob CS. MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jan 4;64:237-49. doi: 10.1016/j.pnpbp.2015.03.011. Epub 2015 Mar 25.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 6, 2013): 12
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 2017
• Actual Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have a diagnosis of Autism Spectrum Disorder.
• Have social anxiety.
• Are at least 21 years old.
• Have completed two years of college-level education or comparable vocational training.
• Are 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.
• Are 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.
• Are willing to be contacted on a daily basis for a week after each experimental session.
• Are willing to provide a contact that is willing and able to be reached by investigators, accompany the subject during some or all of the study visits, and complete study measures.
• Are 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 are able to bear children and do not practice an effective means of birth control.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02008396
• Other Study ID Numbers: MAA-1
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: We will share outcome data appearing in any published reports upon request.
• Supporting Materials: Study Protocol
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Data and study-related documents will be available when all participants have completed the study
• Access Criteria: Interested persons should correspond with the central contact for the study.

• Responsible Party: Multidisciplinary Association for Psychedelic Studies
• Study Sponsor: Multidisciplinary Association for Psychedelic Studies
• Collaborators: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Investigators

• Principal Investigator: Charles S. Grob, MD; University of California, Los Angeles

• PRS Account: Multidisciplinary Association for Psychedelic Studies
• Verification Date: June 2019