Exploring Mechanisms of Action in MDMA-assisted Psychotherapy for PTSD

Completed

• Conditions: Posttraumatic Stress Disorder
• Interventions: Drug: Midomafetamine; Behavioral: Therapy

• Registration Number: NCT02102802
• Lead Sponsor: Lykos Therapeutics

Brief Summary

The goal of this observational sub-study is to provide information on how MDMA-assisted therapy affects the brain and body of people with chronic PTSD.

The main question it aims to answer is: Is PTSD symptom reduction associated with changes in heart rate variability and brain activity?

Participants from the MP-8 study will be invited to enroll in this sub-study where they will undergo an fMRI brain scan and other measurements of body function.

Detailed Description

This exploratory sub-study will identify psychotherapeutic processes occurring during MDMA- assisted psychotherapy in people with chronic PTSD and assess the feasibility of exploring physiological correlates of clinical outcomes in subjects enrolled in the ongoing clinical trial of MDMA-assisted psychotherapy, NCT #: NCT01211405. The sub-study will be conducted in collaboration with researchers at the Medical University of South Carolina (MUSC), Smith College and the New School for Social Research.

To support the clinical outcomes measured by CAPS from the MP-8 study, the sponsor is interested in correlations of outcomes with treatment-related changes in potential biological markers of PTSD, measured by heart rate variability (HRV) and fMRI. Brain activity while listening to neutral and personalized trauma-related scripts will take place at baseline and after experimental MDMA-assisted psychotherapy with low, medium, or full dose MDMA. The fMRI scan will be followed by a Diffusion Tensor Imaging (DTI) scan. After each scanning session, pulse measurements will be extracted as a digital data file from which HRV will be calculated. FMRI scans and HRV measurements will occur at baseline for participants in all conditions, one month after the second experimental session and again after a final experimental session for participants in the low or medium dose condition, and two months after the final experimental session for participants in the full dose condition.

Participants will complete the Self-Compassion Scale, a self-report measure of self-compassion at Baseline and after the final MDMA-assisted psychotherapy session. Psychotherapeutic processes will be assessed via observing psychotherapy and sorting a set of 100 therapy-related items as a means of describing the interactions. Trained coders will observe at least one pre-drug psychotherapy session, one experimental (drug-assisted psychotherapy) session and one post-drug psychotherapy session.

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2014-03-27
• Study First Submitted QC: 2014-03-31
• Study First Posted: 2014-04-03
• Primary Completion: 2015-08-03
• Study Completion: 2015-08-03
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-01
• Last Update Posted: 2024-11-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Enrolled in the parent study, "A Randomized, Triple-Blind, Phase 2 Pilot Study Comparing 3 Different Doses of MDMA in Conjunction with Manualized Psychotherapy in 24 Veterans, Firefighters, and Police Officers with Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)." NCT #: NCT01211405

Exclusion Criteria

• Mass brain lesion
• Have metal in their skulls,
• Having brain or heart pacemakers
• History of major head trauma
• Have past or present panic or extreme discomfort with being in small enclosed spaces (claustrophobia)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
MDMA-assisted therapy	Midomafetamine	Participants undergoing MDMA-assisted therapy in the main study, MP-8 (NCT#01211405)
MDMA-assisted therapy	Therapy	Participants undergoing MDMA-assisted therapy in the main study, MP-8 (NCT#01211405)

Primary Outcome Measures

Name	Time	Method
Change in brain activity measured via fMRI while listening to trauma scripts	Baseline, two months after final experimental session	Brain activity measured via functional magnetic resonance imaging (fMRI) after listening to trauma-related scripts.

Secondary Outcome Measures

Name	Time	Method
Change in heart rate variability in response to trauma script	Baseline, two months post final drug administration	Assessment of Heart rate variability (HRV) in response to trauma-related scripts; a potential physiological correlate of response to treatment for PTSD
Change in Self Compassion Scale Score	Baseline, two months post final drug administration	Self-report measure of self-compassion
Change in brain activity measured via fMRI while listening to trauma scripts	Baseline, one month post-drug	Brain activity measured via functional magnetic resonance imaging (fMRI) after listening to trauma-related scripts

Trial Locations

Locations (1)

Offices of Michael Mithoefer; 🇺🇸 Mount Pleasant, South Carolina, United States