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Trial registered on ANZCTR


Registration number
ACTRN12621001078842
Ethics application status
Approved
Date submitted
30/05/2021
Date registered
16/08/2021
Date last updated
13/04/2024
Date data sharing statement initially provided
16/08/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Australian 3,4-Methylenedioxymethamphetamine (MDMA)-assisted Psychotherapy Study for the Treatment of Posttraumatic Stress Disorder (PTSD)
Scientific title
An Open-Label Feasibility Study to Assess the Safety and Effect of Manualised MDMA-Assisted Psychotherapy for the Treatment of Severe Posttraumatic Stress Disorder among Four Australians
Secondary ID [1] 301880 0
IPAU-1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post Traumatic Stress Disorder 318380 0
Condition category
Condition code
Mental Health 316398 316398 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a proof-of-concept open label trial of MDMA-assisted psychotherapy for the treatment of Posttraumatic Stress Disorder (PTSD) among four people using the Multidisciplinary Association of Psychedelic Studies (MAPS) MDMA-assisted psychotherapy treatment protocol. The treatment period will commence after a baseline measure of PTSD has been obtained using the CAPS-5 and provided in accordance with the MAPS manualised MDMA-assisted psychotherapy over ~12 weeks.

The psychotherapy is provided by a male/female co-therapy team. A total of 15 psychotherapy sessions are provided in each treatment of MDMA-assisted psychotherapy. The psychotherapy sessions are delivered in accordance with the Multidisciplinary Association for Psychedelic Studies’ (MAPS) MDMA-assisted psychotherapy therapy treatment manual, which is underpinned by a humanistic/transpersonal psychotherapy approach. This includes three preparation sessions before the first MDMA session. Each preparation session is ~1.5 hours in duration and occur weekly. Each of the three MDMA sessions involves ~8 hours of drug-assisted psychotherapy and requires an overnight stay. This is followed by an integrative psychotherapy session the next morning at the hospital that is ~1.5 hours in duration. Two additional integrative sessions of non-drug psychotherapy are then provided before and after the second and third MDMA-assisted sessions that also last ~1.5 hours.

Each MDMA session involves the administration of two doses of MDMA that is provided to participants a capsule that is to be taken orally. The first dose is administrated early in the morning within 1 hour of commencing the MDMA session and is followed by a supplementary dose at 2.5 hours after initial administration. The initial doses of MDMA provided in first MDMA sessions is 80 mg of MDMA, followed 1.5 to 2 hours later by a supplemental half-dose (40 mg). The second and third MDMA sessions involve an initial flexible dose of either 80mg or 120mg, depending on the participant's response to the first MDMA session, followed 1.5 to 2 hours later by a supplemental half-dose (40 mg or 60mg). The MDMA will be provided to participants in a capsule.

The first MDMA session should occur about ~4 weeks after a baseline measure of PTSD has been obtained using the CAPS-5, after which time the preparation sessions will have been also completed. These sessions involve the co-therapy teams understanding the nature of the index trauma, providing the participant with information about the effects of MDMA in the context of MDMA-assisted psychotherapy and assisting the participant develop their intention for the MDMA session. These sessions are completing in accordance with the MAPS MDMA-assisted psychotherapy therapy treatment manual. The second MDMA session should occur within ~3 weeks of the first MDMA session and the third MDMA session should occur within ~3 weeks of the second MDMA sessions.

Participants are required to agree to a range of lifestyle modifications prior to engaging in the treatment and a checklist of these lifestyle modifications is completed prior to each MDMA session (including a urine screen for illicit drug use and pregnancy). The administration of the MDMA is overseen by the co-therapy team, a psychiatrist, and a nurse.
Intervention code [1] 318170 0
Treatment: Drugs
Intervention code [2] 320937 0
Behaviour
Intervention code [3] 321246 0
Treatment: Other
Comparator / control treatment
No Control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 324550 0
Adherence to the Multidisciplinary Association of Psychedelic Studies (MAPS) MDMA-assisted psychotherapy treatment as assessed by the MAPS MDMA-assisted psychotherapy auditing tool.
Timepoint [1] 324550 0
The duration of the research.
Primary outcome [2] 324551 0
Treatment fidelity will be gathered through evaluating the effect of MDMA-assisted psychotherapy on PTSD, as measured by the change in CAPS-5 Total Severity Score.
Timepoint [2] 324551 0
At baseline and within 2 weeks post-treatment completion.
Secondary outcome [1] 396265 0
The secondary objective is to evaluate the effect of MDMA-assisted psychotherapy for PTSD in clinician-rated functional impairment, as measured by the change in Sheehan Disability Scale (SDS).
Timepoint [1] 396265 0
At baseline and within 2 weeks post-treatment completion.
Secondary outcome [2] 396266 0
The overall safety objective is to assess severity, incidence and frequency of AEs, AEs of Special Interest (AESIs), and Serious Adverse Events (SAEs) through monitoring participants heart rate and blood pressure during MDMA-assisted psychotherapy sessions using a sphygmomanometer.
Timepoint [2] 396266 0
Heart rate and blood pressure will be measured at four time points during each MDMA-assisted psychotherapy session: before being administered the MDMA, 2 hours after the initial administration, 8 hours after the initial administration and 24 hours after time point 1 (baseline).
Secondary outcome [3] 397873 0
The overall safety objective is to assess severity, incidence and frequency of AEs, AEs of Special Interest (AESIs), and Serious Adverse Events (SAEs) through monitoring participants' suicidality for the duration of the study using the Columbia Suicide Severity Rating Scale.
Timepoint [3] 397873 0
The Columbia Suicide Severity Rating Scale will be administered at baseline, then a week before each MDMA session, immediately prior to the MDMA session, and 24 hours after the MDMA session. It will also be administered prior to the participant

Eligibility
Key inclusion criteria
1. A diagnosis of current PTSD for more than 6 months.
2. Have PTSD symptoms in the last month based on PCL-5 total score of 35 or greater.
3. Are fluent in speaking and reading the predominantly used or recognised language of the study site.
4. Are able to swallow pills.
5. Agree to the study visits being video recorded, including MDMA Sessions, Independent Rater assessments and non-drug psychotherapy sessions.
6. If of childbearing potential, must have a negative pregnancy test at study entry and prior to each MDMA Session, and must agree to use adequate birth control through 10 days after the last MDMA Session. Not of childbearing potential is defined as permanent sterilisation, postmenopausal, or assigned male at birth.
7. Agree to the following lifestyle modifications: comply with requirements for fasting and refraining from certain medications prior to MDMA Sessions, not participate in any other interventional clinical trials during the duration of the study, remain overnight at the study site after each MDMA Session and be driven home after, and commit to medication dosing, therapy, and study procedures.
8. Have attempted to engage in at least one evidence-based psychotherapy for PTSD and trialled one medication.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Is unable to give adequate informed consent.
2. Are currently engaged in compensation litigation whereby financial gain would be achieved from prolonged symptoms of PTSD or any other psychiatric disorders.
3. Are likely, in the investigator’s opinion and via observation during the Preparatory Period, to be re-exposed to their index trauma or other significant trauma, lack social support, or lack a stable living situation.
4. Have used Ecstasy (material represented as containing MDMA) more than 10 times within the last 10 years or at least once within 6 months of the first MDMA Session; or have previously participated in a MAPS-funded MDMA clinical trial.
5. Have any current problem which, in the opinion of the investigator or Medical Monitors, might interfere with participation.
6. Are prescribed a psychotropic medication that could adversely interact with MDMA.
7. Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrolment.
8. Have a history of, or a current primary psychotic disorder, bipolar affective disorder type 1 assessed via MINI or dissociative identity disorder.
9. Have a current eating disorder with active purging.
10. Have current major depressive disorder with psychotic features.
11. Have an active substance use disorder for any substance other than caffeine or nicotine in the past 60 days
12. Have a Personality Disorders
13. Is presenting current serious acute suicide risk
14. Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist.
15. Require ongoing concomitant therapy with a psychiatric medication that could adversely interact with MDMA.
16. Have evidence or history of significant (controlled or uncontrolled) haematological, endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, renal, gastrointestinal, immunocompromising, or neurological disease, including seizure disorder, or any other medical disorder judged by the investigator to significantly increase the risk of MDMA administration or be likely to produce significant symptoms that during the study could interfere with participation or be confused with side effects of MDMA (participants with hypothyroidism who are on adequate and stable thyroid replacement will not be excluded). Note: if participants present with a history of glaucoma, enrolment would be allowed only with the approval of their ophthalmologist
17. Have uncontrolled hypertension using the standard criteria of the American Heart Association (values of 140/90 millimetres of Mercury [mmHg] or higher assessed on three separate occasions).
18. Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds corrected by Bazett’s formula).
19. Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome).
20. Have symptomatic liver disease.
21. Have history of hyponatremia or hyperthermia.
22. Weigh less than 48 kilograms.
23. Are pregnant or breastfeeding, or are of childbearing potential and are not practising an effective means of birth control.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive statistics will be provided for each participant. Given the small sample size, the scores of the primary outcomes for each participant from baseline to post-treatment will be compared using the Wilcoxon signed rank test. Hedge’s g will be used as a conservative measure of effect size given the sensitivity of Cohen’s d to small sample sizes. The percentage of participants no longer meeting criteria for PTSD or exhibiting subthreshold symptoms at the endpoint, as determined by a CAPS-5 scoring manual, will be used to describe the clinical effect of the treatment.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/12/2021
Actual
19/05/2022
Date of last participant enrolment
Anticipated
1/12/2024
Actual
Date of last data collection
Anticipated
1/05/2025
Actual
Sample size
Target
4
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 19600 0
Abbotsford Private Hospital - West Leederville
Recruitment postcode(s) [1] 34216 0
6007 - West Leederville

Funding & Sponsors
Funding source category [1] 306300 0
University
Name [1] 306300 0
Edith Cowan University
Country [1] 306300 0
Australia
Funding source category [2] 308725 0
Hospital
Name [2] 308725 0
Abbotsford Private Hospital
Country [2] 308725 0
Australia
Primary sponsor type
University
Name
Edith Cowan University
Address
270 Joondalup Drive
Joondalup
WA 6027
Country
Australia
Secondary sponsor category [1] 309624 0
None
Name [1] 309624 0
Address [1] 309624 0
Country [1] 309624 0
Other collaborator category [1] 281812 0
University
Name [1] 281812 0
Murdoch University
Address [1] 281812 0
90 South St
Murdoch
WA 6150
Country [1] 281812 0
Australia
Other collaborator category [2] 281813 0
Charities/Societies/Foundations
Name [2] 281813 0
Psychedelic Research In Science & Medicine (PRISM) Ltd.
Address [2] 281813 0
Po Box 72
Balwyn North VIC 3104
Australia
Country [2] 281813 0
Australia
Other collaborator category [3] 281814 0
Charities/Societies/Foundations
Name [3] 281814 0
Multidisciplinary Association for Psychedelic Studies
Address [3] 281814 0
3141 Stevens Creek Blvd #40563
San Jose
CA 95117
Country [3] 281814 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306515 0
Bellberry
Ethics committee address [1] 306515 0
123 Glen Osmond Rd
Eastwood
SA 5063
Ethics committee country [1] 306515 0
Australia
Date submitted for ethics approval [1] 306515 0
05/11/2019
Approval date [1] 306515 0
14/05/2020
Ethics approval number [1] 306515 0

Summary
Brief summary
The objective of this investigator-initiated study is to determine whether an Australian treatment team can safely and effectively deliver 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy to patients with treatment-refractory posttraumatic stress disorder (PTSD) through training and ongoing mentoring from the Multidisciplinary Association for Psychedelic Studies (MAPS). MAPS is a non-profit research and educational organisation working to obtain approval for the prescription use of 3,4-methylenedioxymethamphetamine (MDMA) as an adjunct to psychotherapy in patients with posttraumatic stress disorder (PTSD). It uses an open-label design to assess the feasibility of safely and effectively providing MDMA-assisted psychotherapy in Australia by treating four Western Australian adults with chronic treatment-resistant PTSD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104126 0
Dr Stephen Bright
Address 104126 0
Edith Cowan University
270 Joondalup Drive
Joondalup
WA 6027
Country 104126 0
Australia
Phone 104126 0
+61863042597
Fax 104126 0
Email 104126 0
s.bright@ecu.edu.au
Contact person for public queries
Name 104127 0
Dr Stephen Bright
Address 104127 0
Edith Cowan University
270 Joondalup Drive
Joondalup
WA 6027
Country 104127 0
Australia
Phone 104127 0
+61863042597
Fax 104127 0
Email 104127 0
s.bright@ecu.edu.au
Contact person for scientific queries
Name 104128 0
Dr Stephen Bright
Address 104128 0
Edith Cowan University
270 Joondalup Drive
Joondalup
WA 6027
Country 104128 0
Australia
Phone 104128 0
+61863042597
Fax 104128 0
Email 104128 0
s.bright@ecu.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All outcome measures
When will data be available (start and end dates)?
The electronic data file will be locked after the last piece of data has been entered on 1/5/2023. Once it has been locked the IPD will be available until 1/1/2028
Available to whom?
Any researcher upon request.
Available for what types of analyses?
To achieve the aims of an approved proposal.
How or where can data be obtained?
By emailing the principal investigator (s.bright@ecu.edu.au)


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.