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

Phase 2

Completed

Conditions: Social Anxiety in Autistic Adults

Interventions: Drug: Placebo
Drug: Midomafetamine HCl
Behavioral: Therapy

Registration Number: NCT02008396

Lead Sponsor: Lykos Therapeutics

Brief Summary: The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective at reducing social anxiety in adults with autism.

The main questions it aims to answer are:

* Do two sessions of MDMA-assisted therapy reduce social anxiety?

* What dose of MDMA is most effective at reducing social anxiety?

Researchers will compare two blinded sessions of MDMA-assisted therapy to two blinded sessions of placebo with therapy.

Participants will undergo three non-drug preparatory therapy sessions before the first blinded medication session. After each medication session, participants will undergo three non-drug integrative therapy sessions.

In Stage 2, participants who received placebo with therapy in the first two blinded sessions will be able to undergo two sessions with MDMA-assisted therapy.

Detailed Description: 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, with 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, participants (Group 1) were randomized to receive one dose of either placebo or 75 mg of midomafetamine HCl. In the second experimental session one month later, Group 1 subjects randomized to MDMA escalated to 100 mg of midomafetamine HCl, unless contraindicated. The second group of subjects enrolled (Group 2) were randomized to receive one dose of either placebo or 100 mg of midomafetamine HCl. In the second experimental session one month later, Group 2 subjects randomized to MDMA escalated to 125 mg of midomafetamine HCl, 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-assisted therapy scheduled one month apart. Subjects received 75 mg of midomafetamine HCl in the first session and escalated to 125 mg of midomafetamine HCl in the second session, unless contraindicated.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Inactive Placebo with Therapy	Placebo	Participants will receive inactive placebo during two psychotherapy sessions lasting approximately 7 hours.
Inactive Placebo with Therapy	Therapy	Participants will receive inactive placebo during two psychotherapy sessions lasting approximately 7 hours.
Group 1: MDMA-assisted therapy 75 mg/100mg	Midomafetamine HCl	Participants will receive 75 mg and 100 mg midomafetamine HCl during two sessions of MDMA-assisted therapy, respectively, lasting approximately 7 hours.
Group 1: MDMA-assisted therapy 75 mg/100mg	Therapy	Participants will receive 75 mg and 100 mg midomafetamine HCl during two sessions of MDMA-assisted therapy, respectively, lasting approximately 7 hours.
Group 2: MDMA-assisted therapy 100 mg/125 mg	Midomafetamine HCl	Participants will receive 100 mg and 125 mg midomafetamine HCl during two sessions of MDMA-assisted therapy, respectively, lasting approximately 7 hours.
Group 2: MDMA-assisted therapy 100 mg/125 mg	Therapy	Participants will receive 100 mg and 125 mg midomafetamine HCl during two sessions of MDMA-assisted therapy, respectively, lasting approximately 7 hours.

Primary Outcome Measures

Name	Time	Method
Liebowitz Social Anxiety Scale (LSAS) Total Score 1-Month Post Experimental Session 2	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	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.

Secondary Outcome Measures