Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05709353




Registration number
NCT05709353
Ethics application status
Date submitted
20/01/2023
Date registered
2/02/2023
Date last updated
7/11/2023

Titles & IDs
Public title
MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder
Scientific title
A Randomised, Controlled Trial of MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder
Secondary ID [1] 0 0
X22-0121
Universal Trial Number (UTN)
Trial acronym
MPATHY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
PTSD 0 0
Alcohol Use Disorder 0 0
Alcohol Dependence 0 0
Post-traumatic Stress Disorder 0 0
Comorbidities and Coexisting Conditions 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Addiction
Mental Health 0 0 0 0
Anxiety
Mental Health 0 0 0 0
Other mental health disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Mental Health 0 0 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Behaviour - Prolonged exposure therapy
Treatment: Drugs - MDMA
Treatment: Drugs - Niacin

Experimental: 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

Other: 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


Behaviour: 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.

Treatment: Drugs: 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.

Treatment: Drugs: Niacin
Administration of niacin 250mg or niacin-matched placebo during two 'dosing' sessions.
Intervention code [1] 0 0
Behaviour
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
52 weeks
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
52 weeks
Secondary outcome [1] 0 0
Number of Heavy Drinking Days per week (HDDs) (>5 standard drinks/day for men; >4 for women)
Timepoint [1] 0 0
52 weeks
Secondary outcome [2] 0 0
Absence of any HDD
Timepoint [2] 0 0
52 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/09/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2026
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Drug Health Services, Royal Prince Alfred Hospital - Sydney
Recruitment hospital [2] 0 0
Turning Point - Richmond
Recruitment postcode(s) [1] 0 0
2050 - Sydney
Recruitment postcode(s) [2] 0 0
3121 - Richmond

Funding & Sponsors
Primary sponsor type
Other
Name
University of Sydney
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Monash University
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Sydney Local Health District
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05709353
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Kirsten C Morley, PhD
Address 0 0
University of Sydney
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kirsten C Morley, PhD
Address 0 0
Country 0 0
Phone 0 0
61295153636
Fax 0 0
Email 0 0
Kirsten.morley@sydney.edu.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05709353