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

NCT ID: NCT05709353

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-19
• Study Completion Date: 2026-05-31

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).

Conditions

PTSD; Alcohol Use Disorder; Alcohol Dependence; Post-traumatic Stress Disorder; Comorbidities and Coexisting Conditions

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

COPE + MDMA

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

Group Type: EXPERIMENTAL

Prolonged exposure therapy

Intervention Type: 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.

MDMA

Intervention Type: 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.

COPE + Niacin (Control)

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

Group Type: OTHER

Prolonged exposure therapy

Intervention Type: 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.

Niacin

Intervention Type: DRUG

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

Interventions

Prolonged exposure therapy

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.

Intervention Type: BEHAVIORAL

MDMA

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.

Intervention Type: DRUG

Niacin

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

Intervention Type: DRUG

Other Intervention Names

COPE (Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure); 3,4-Methyl enedioxy methamphetamine; Control, Vitamin B3

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Monash University

OTHER

Sponsor Role: collaborator

Sydney Local Health District

OTHER_GOV

Sponsor Role: collaborator

University of Sydney

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kirsten C Morley, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Sydney

Locations

Drug Health Services, Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

Site Status: RECRUITING

Turning Point

Richmond, Victoria, Australia

Site Status: NOT_YET_RECRUITING

Countries

Australia

Central Contacts

Kirsten C Morley, PhD

Role: CONTACT

Kirsten.morley@sydney.edu.au

61295153636

Ellen Towers

Role: CONTACT

ellen.towers@sydney.edu.au

Facility Contacts

Paul Haber, MBBS

Role: primary

paul.haber@sydney.edu.au

Shalini Arunogiri, MBBS

Role: primary

shaliniA@turningpoint.org.au

Other Identifiers

X22-0121

Identifier Type: -

Identifier Source: org_study_id