MDMA-assisted Cognitive Processing Therapy Versus Cognitive Processing Therapy for Veterans With Severe Posttraumatic Stress Disorder

Official title

A Randomized Trial to Compare MDMA-assisted Cognitive Processing Therapy (aCPT) Versus a VA Standard-of-care CPT for the Treatment of Severe Posttraumatic Stress Disorder Among Veterans

Overview

In partnership with the Veterans Affairs (VA) Palo Alto Health Care System and Stanford University, this study aims to evaluate clinical outcomes, assess implementation feasibility, and health economics of MDMA-assisted Cognitive Processing Therapy (MDMA-aCPT) in the treatment of posttraumatic stress disorder (PTSD). Through a randomized comparison of MDMA-aCPT versus Cognitive Processing Therapy (CPT), a VA gold standard treatment for PTSD, the proposed study will set the stage for understanding the potential use and application of MDMA-aCPT for PTSD within the VA system.

Detailed description

Posttraumatic stress disorder (PTSD) is a serious debilitating disorder that negatively impacts a person's daily life, and can result in diminished cognitive and psychosocial functioning, fractured relationships, inability to maintain employment, substance use disorders, high-cost healthcare utilization, increased depression, and suicide risk. People who suffer from PTSD relive their traumatic experience(s) through nightmares and flashbacks, have difficulty sleeping, and feel detached or estranged. Symptoms can be severe and long lasting.

Many available PTSD treatments, including medications and therapy, effectively treat only a fraction of people who try them. This indicates a need to assess treatments targeting durable remission of PTSD. An extensive list of medications, namely antipsychotics, anxiolytics, antidepressants, and sleep aids, are frequently prescribed off-label but are minimally effective in reducing PTSD symptoms.

Cognitive Processing Therapy (CPT) is a cognitively-oriented approach to treating PTSD developed in the late 1980's by Dr. Patricia Resick. Significant research on CPT has been conducted in the VA system nationally. Across a number of studies, a meta-analysis found the number of subjects that no longer meet PTSD criteria after receiving a full course of CPT ranged from 30% to 97%, and 51% of subjects receiving CPT achieved loss of diagnosis compared to waitlist, self-help booklets, and treatment as usual control groups. There are various task forces and active efforts to deploy CPT more broadly in the VA.

MDMA-assisted cognitive processing therapy (MDMA-aCPT) is a novel treatment package that combines standard CPT with the administration of MDMA (3,4-methylenedioxymethamphetamine) during medication sessions separate from CPT sessions. This includes the regular course of 8-15 CPT sessions, three sessions during which MDMA is used, and an additional one 'preparatory' session and three 'integration' sessions without the use of medication. Data from a series of Phase 2 and Phase 3 studies of MDMA-assisted therapy provide preliminary evidence suggesting that chronic PTSD symptoms are improved by up to three sessions of MDMA-assisted therapy and associated non-drug preparatory and integrative therapy sessions.

Our goal is to learn how MDMA-aCPT compares to CPT in reducing PTSD symptoms among Veterans. Comparing MDMA-aCPT and CPT for the treatment of PTSD is particularly important due to the urgent need for effective treatments within the VA system.

PTSD carries a high public burden, both economically and socially, by increased healthcare utilization, use of social services, lost wages, and disability payments. Given the chronicity of PTSD, low treatment compliance evidenced by high dropouts, and limited recovery with current medications contributing to serious outcomes, PTSD patients exhibit an unmet medical need. Currently, the VA serves approximately nine million Veterans and the conservative estimate of those with PTSD is 25%, or over two million Veterans. The potential importance and benefits of this novel treatment to Veterans, doctors, researchers, and the VA system cannot be underestimated. The clinical effectiveness, implementation evaluation, and economic assessment conducted in this study will provide critical information and understanding of the feasibility of utilization in the VA system.

Interventions

• Drug MDMA
  Participants will receive a flexible divided-dose of MDMA HCl plus therapy at three Experimental Sessions, as well as non-drug Preparatory and Integration Sessions
• Behavioral Cognitive Processing Therapy
  Participants will receive 8-15 (average of 12) sessions of Cognitive Processing Therapy
• Behavioral MDMA-assisted Cognitive Processing Therapy (MDMA-aCPT)
  Participants assigned to MDMA-aCPT will undergo a therapeutic approach administered by trained therapists. MDMA seems to engender internal awareness that even painful feelings that arise are an important part of the therapeutic process. MDMA can elicit feelings of empathy, love, and deep appreciation, along with a clearer perspective of the trauma as a past event, a more accurate perspective about its significance, and a heightened awareness of the support and safety that exists in the present.

Primary outcome measures

• Change in Clinician Administered PTSD Scale (CAPS-5) Total Severity Score [Time frame: From Baseline to approximately 4 months post-baseline]

Secondary outcome measures (1)

• Change in Quality of Life Enjoyment and Satisfaction Questionnaire [Time frame: From Baseline to approximately 4 months post-baseline]

Eligibility criteria

Inclusion criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

• Are at least 18 years at the time of signing the informed consent
• Are a U.S Military Veteran
• Are receiving services from VA Palo Alto Healthcare System, VA San Francisco Healthcare System, or VA NorCal Healthcare System
• Are fluent in speaking and reading in English
• Agree to have study visits audio and/or video recorded
• If assigned to MDMA-aCPT, able to identify appropriate support person(s) to stay with the participant on the evenings of the MDMA sessions
• Meet DSM-5 criteria for PTSD with a symptom duration of at least 6 months
• Have severe PTSD symptoms in the last month
• Body weight of at least 48 kilograms (kg)
• Is not pregnant, planning to get pregnant, or breastfeeding
• Capable of giving signed informed consent

Exclusion criteria

Participants are excluded from the study if any of the following criteria apply:

• Have a history of any medical condition that could make receiving a sympathomimetic drug harmful
• Have current unstable medical illness
• Have cardiac conditions, including uncontrolled hypertension, prolonged QTc interval, and other cardiac conditions
• Have received Electroconvulsive Therapy (ECT), ketamine-assisted therapy, or used ketamine within 12 weeks of enrollment
• Moderate or severe alcohol or cannabis use disorder within the last 12 months
• Active illicit drug (other than cannabis) or prescription drug substance use disorder at any severity within the last 12 months
• Have current serious suicide risk
• Unable or unwilling to stop or safely taper off prohibited medications
• Have used MDMA (ecstasy) ever
• Currently enrolled in any clinical study
• Personal history of primary psychotic disorder, type I bipolar disorder, severe personality disorder, eating disorder with compensatory behaviors, or depressive disorder with psychotic features
• Lack social support, or lack a stable living situation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 1 center

• VA Palo Alto Health Care System / Stanford University — Palo Alto

Identifiers

NCT: NCT05837845 · SUP0023APR

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗