MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder

NCT05709353 | Recruiting Phase 2 DMC

• 1 other identifier: X22-0121
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (2)

• 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.

  CAPS-5 is a structured diagnostic interview with excellent psychometric properties and diagnostic efficiency and used widely in MDMA-assisted PTSD studies. The CAPS-5 will be administered by independent evaluators blind to treatment condition. CAPS-5 total symptom severity score is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms. CAPS-5 symptom cluster severity scores are calculated by summing the individual item severity scores for symptoms corresponding to a given DSM-5 cluster: Criterion B (items 1-5); Criterion C (items 6-7); Criterion D (items 8-14); and, Criterion E (items 15-20).

  52 weeks

• 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.

  PCL-5 has excellent psychometric characteristics for a secondary indicator of PTSD symptom severity. Items are summed to provide a total severity score (range = 0-80). The PCL-5 can determine a provisional diagnosis in two ways: Summing all 20 items (range 0-80) and using a cut-point score of 31-33 appears to be reasonable based upon current psychometric work.

  52 weeks

Secondary Outcomes (2)

• Number of Heavy Drinking Days per week (HDDs) (>5 standard drinks/day for men; >4 for women)

  52 weeks

• Absence of any HDD

  52 weeks

Other Outcomes (19)

• Mean alcohol consumption per drinking day

  52 weeks

• Change in dependence Severity

  52 weeks

• Changes in Anxiety

  52 weeks

Study Arms (2)

COPE + MDMA

EXPERIMENTAL

4x COPE sessions Dose 1: 2x MDMA capsules (80mg) + 1x niacin-matched placebo capsule Optional supplementary dispense: 1x MDMA capsule (40mg) 4x COPE sessions Dose 2: 2x MDMA capsules (80mg) + 1x niacin-matched placebo capsule Optional supplementary dispense: 1x OR 2x white MDMA capsule (40 or 80mg) 4x COPE sessions

Behavioral: Prolonged exposure therapy; Drug: MDMA

COPE + Niacin (Control)

OTHER

4x COPE sessions Dose 1: 2x MDMA-matched placebo capsules + 1x niacin capsule (250mg) Optional supplementary dispense: 1x MDMA-matched placebo capsule 4x COPE sessions Dose 2: 2x MDMA-matched placebo capsules + 1x niacin capsule (250mg) Optional supplementary dispense: 1x OR 2x MDMA-matched placebo capsule 4x COPE sessions

Behavioral: Prolonged exposure therapy; Drug: Niacin

Interventions

Prolonged exposure therapy BEHAVIORAL

COPE represents an integration of existing evidence-based manualised CBT interventions for PTSD and substance dependence (see manual DOI: 10.1093/med:psych/9780199334513.001.0001). COPE used in the current study will represent an integration of existing evidence-based manualised CBT interventions for PTSD and substance dependence. COPE only begins when the participant in a safe environment and no longer in contact with the traumatic event/exposure. COPE employs imaginal and in vivo exposures to treat PTSD and consists of 12 individual 90-minute sessions (i.e. 19.5 hours) delivered by a clinical psychologist.

Also known as: COPE (Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure)

COPE + MDMA; COPE + Niacin (Control)

MDMA DRUG

Administration of 80 to 160 mg MDMA across two 'dosing' sessions. Supplemental doses (additional 40mg during first session, additional 40- 80mg during second session) will be dependent on clinician and participant consensus during preparatory period of 'dosing session'. These supplemental amounts will be dispensed 60 to 90 minutes after initial 80 mg dose.

Also known as: 3,4-Methyl enedioxy methamphetamine

COPE + MDMA

Niacin DRUG

Administration of niacin 250mg or niacin-matched placebo during two 'dosing' sessions.

Also known as: Control, Vitamin B3

COPE + Niacin (Control)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Aged ≥18 years old
• Adequate cognition and English language skills to give valid consent and complete research interviews assessments
• Willing to give written informed consent
• Received prior treatment for PTSD or AUD (not including study interventions)
• Stable housing
• 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

You may not qualify if:

• 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
• Pregnant or lactating (contraception must be used and a sensitive pregnancy test will be performed at baseline and prior to dosing)
• Significant alcohol withdrawal (current Clinical Institute Withdrawal Assessment for Alcohol \[CIWA-Ar\] score ≥10, including history of delirium tremens or alcohol withdrawal seizures).
• 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)
• 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)
• Substance use disorder other than tobacco (e.g. benzodiazepines, cannabis)
• 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)
• 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
• Clinically unstable systemic medical (e.g., cancer) or psychiatric disorder or condition that might require hospitalisation that precludes trial participation
• Regular use of ecstasy (e.g. at least twice in last 6 months, or \>10 times within the last 5 years)
• Enrolled in any other interventional clinical trials in the previous two months or over the duration of the study

Sponsors & Collaborators

• University of Sydney: lead
• Monash University: collaborator
• Sydney Local Health District: collaborator

Study Sites (2)

Drug Health Services, Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

RECRUITING

Turning Point

Richmond, Victoria, 3121, Australia

NOT YET RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Alcoholism

Interventions

N-Methyl-3,4-methylenedioxyamphetamine; Niacin; Niacinamide

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Kirsten C Morley, PhD

  University of Sydney

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kirsten C Morley, PhD

CONTACT

61295153636; Kirsten.morley@sydney.edu.au

Ellen Towers

CONTACT

ellen.towers@sydney.edu.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised, double-blind between group comparison of change in PTSD symptoms and alcohol consumption

Study Record Dates

• First Submitted: January 20, 2023
• First Posted: February 2, 2023
• Study Start: September 19, 2023
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: November 7, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)