Clinical trial NCT05709353: MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder
Official title: A Randomised, Controlled Trial of MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: PTSD
Alcohol Use Disorder
Alcohol Dependence
Post-traumatic Stress Disorder
Comorbidities and Coexisting Conditions
Keywords: MDMA-assisted therapy
Randomised-Controlled Trial
Comorbid PTSD and AUD
MDMA
COPE
Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure
Psychedelic-Assisted Therapy
Lead sponsor: University of Sydney
Sponsor class: OTHER
Collaborators: name: Monash University
name: Sydney Local Health District
First posted: 2023-02-02
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, double-blind between group comparison of change in PTSD symptoms and alcohol consumption
Primary purpose: TREATMENT

Brief summary: To explore the effectiveness of of MDMA-assisted prolonged exposure therapy in improving treatment outcomes for individuals with comorbid PTSD and alcohol use disorder in a double-blind randomised placebo-controlled trial.

Detailed description: New strategies for the treatment of comorbid PTSD and alcohol dependence are urgently required. Recent evidence has shown strong support for trauma-focused integrated treatments (namely COPE), however, only 49% demonstrate clinically significant improvements. MDMA may be a promising approach to improve response to COPE for this population. Emerging evidence suggests that MDMA-assisted therapy may be of promise for PTSD, and has demonstrated a good safety profile and potential efficacy in alcohol dependence.

This project will evaluate the clinical efficacy and tolerability of MDMA-assisted COPE relative to a control-assisted COPE. Active control used in this study is niacin. The investigators hypothesise that MDMA treated participants will be have a reduction in PTSD symptom severity as well as heavy drinking.

The trial will utilise a double blind, randomised, controlled design. A sample of 120 individuals will receive 14 weeks of treatment including 12 COPE sessions and 2 dosing sessions with MDMA (80-160mg) or control (niacin 250mg).

Eligibility criteria: Inclusion Criteria:

1. Both AUD and current PTSD according to the DSM-5 criteria, for 6 months or longer with at least moderate severity, according to investigator judgement and CAPS-5
2. Aged ≥18 years old
3. Adequate cognition and English language skills to give valid consent and complete research interviews assessments
4. Willing to give written informed consent
5. Received prior treatment for PTSD or AUD (not including study interventions)
6. Stable housing
7. Able to identify a significant other (such as a family/friend/partner) who could accompany them from clinic/provide transport and/or be contacted by the study team if required

Exclusion Criteria:

1. History of, or currently meeting, DSM-5 criteria for:

   * current or lifetime psychotic or bipolar disorders, or
   * major depression with psychotic features Assessed via Structured Clinical Interview for DSM-5 - Research Version (SCID-5-RV). Potential participants will be screened for personality disorders but suitability will then be confirmed by clinical interview given the prevalence of high scores in this comorbid population
2. Pregnant or lactating (contraception must be used and a sensitive pregnancy test will be performed at baseline and prior to dosing)
3. Significant alcohol withdrawal (current Clinical Institute Withdrawal Assessment for Alcohol \[CIWA-Ar\] score ≥10, including history of delirium tremens or alcohol withdrawal seizures).
4. Concurrent use of psychotropic medication (antidepressants and alcohol pharmacotherapy use considered if assessed by physician and titrated down with 5 half-lives + 1 week washout)
5. Use of, and unable or unwilling to cease, any medications likely to interact with MDMA in the opinion of the physicians and investigators during the trial (low dose opiates are permitted for pain management but not the night before or after MDMA sessions)
6. Substance use disorder other than tobacco (e.g. benzodiazepines, cannabis)
7. Abnormal clinical findings including a history of, or current: cardiac disease and/or dysrhythmia, uncontrolled hypertension or severe hypotension, abnormal electrocardiogram findings, stroke, liver disease, a history of epilepsy, hyponatraemia, or malignant hyperthermia (controlled hypertension and diabetes type II may be permitted)
8. Suicide risk according to clinician judgement and responses to Columbia Suicide Severity Rating Scale-Lifetime (C-SSRS-L) and SCID-5-RV.

   • Details surrounding any previous attempts \>6 months ago will be gathered whereby attempts related to their trauma/PTSD and/or associated with the use of psychostimulants will contribute to risk assessment and guide trial safety measures if enrolled
9. Clinically unstable systemic medical (e.g., cancer) or psychiatric disorder or condition that might require hospitalisation that precludes trial participation
10. Regular use of ecstasy (e.g. at least twice in last 6 months, or \>10 times within the last 5 years)
11. Enrolled in any other interventional clinical trials in the previous two months or over the duration of the study

Primary outcomes:
measure: change in clinician-rated PTSD severity via Clinician-Administered PTSD Scale for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) (CAPS-5) from baseline to visit 16.
timeFrame: 52 weeks
measure: change in self-reported PTSD symptom severity via Post-Traumatic Stress Disorder Checklist for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) (PCL-5) from baseline to visit 16.
timeFrame: 52 weeks
Secondary outcomes:
measure: Number of Heavy Drinking Days per week (HDDs) (>5 standard drinks/day for men; >4 for women)
timeFrame: 52 weeks
measure: Absence of any HDD
timeFrame: 52 weeks
Other outcomes:
measure: Mean alcohol consumption per drinking day
timeFrame: 52 weeks
measure: Change in dependence Severity
timeFrame: 52 weeks
measure: Changes in Anxiety
timeFrame: 52 weeks
measure: Changes in Depression
timeFrame: 52 weeks
measure: Changes in Stress
timeFrame: 52 weeks
measure: Sleep Disturbances
timeFrame: 52 weeks
measure: Drinking Diary
timeFrame: 16 weeks
measure: Mood states
timeFrame: 16 weeks
measure: Mood following dosing session
timeFrame: week 5, week 10
measure: Changes in Suicidal Ideation
timeFrame: 52 weeks
measure: Changes in Quality of Life
timeFrame: 16 weeks
measure: Changes PTSD cognitions
timeFrame: 52 weeks
measure: Changes in use of Health Services
timeFrame: 16 weeks
measure: Therapeutic Alliance between therapist
timeFrame: 16 weeks
measure: COPE Session Rating Scale
timeFrame: 16 weeks
measure: Treatment Satisfaction as measured by the YES (your experience of service).
timeFrame: 16 weeks
measure: Treatment Satisfaction ss measured by the CSQ-8 (client satisfaction questionnaire).
timeFrame: 16 weeks
measure: Measurement of Distress ss measured by a Likert Scale
timeFrame: week 5, week 12
measure: Measurement of Drug Effect as measured by the Revised Mystical Experience Questionnaire 30 (MEQ-30)
timeFrame: week 5, week 12
Locations:
city: Sydney
country: Australia
facility: Drug Health Services, Royal Prince Alfred Hospital
state: New South Wales
city: Richmond
country: Australia
facility: Turning Point
state: Victoria
Study officials:
affiliation: University of Sydney
name: Kirsten C Morley, PhD
role: PRINCIPAL_INVESTIGATOR
References: