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Trial registered on ANZCTR


Registration number
ACTRN12612000219886
Ethics application status
Submitted, not yet approved
Date submitted
16/02/2012
Date registered
21/02/2012
Date last updated
12/11/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Drug assisted psychotherapy to treat posttraumatic stress disorder in war veterans, using 3,4-methylenedioxymethamphetamine (commonly known as MDMA).
Scientific title
A Randomised, Double-Blind, Active Placebo-Controlled Phase 2 Pilot Study of MDMA-Assisted Manualised Psychotherapy in Australian War Veterans with Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD).
Secondary ID [1] 279955 0
Nil
Universal Trial Number (UTN)
U1111-1128-2389
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic, treatment resistant Posttraumatic Stress Disorder (PTSD) in war veterans. 285871 0
Condition category
Condition code
Mental Health 286057 286057 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a two arm, randomised, multi-dose study with an additional open label lead-in for two participants.

The open label lead-in will involve two participants receiving two experimental drug-assisted psychotherapy sessions of approximately eight hours duration each, using the full dose of 125mg 3,4-methylenedioxymethamphetamine (MDMA) with an optional supplemental dose 2.5 hours later of 62.5mg MDMA (cumulative dose 187.5mg, administered as capsules). At the commencement of each experimental session the participant will undergo a urine drug screen and pregnancy test, a psychological assessment and then begin acclimatising to the environment. The MDMA will be administered soon afterwards, approximately 30-60 minutes after the session begins.

The two drug-assisted psychotherapy sessions will be 3-5 weeks apart and form part of a 12 session treatment over six months, which includes 10 non-drug psychotherapy sessions of 90 minutes duration for preparatory, integrative and follow-up purposes. The session sequence will be as follows.

Sessions 1,2,3: Non-drug preparatory psychotherapy.
Session 4: Experimental drug-assisted psychotherapy.
Sessions 5,6,7: Non-drug integrative psychotherapy.
Session 8: Experimental drug-assisted psychotherapy.
Sessions 9,10,11: Non-drug integrative psychotherapy.
Session 12: Non-drug follow-up psychotherapy.

The aim of the open label lead-in is to verify therapist adherence to the psychotherapy manual prior to proceeding with Stage 1.

Stage 1 is double-blinded and will compare 125mg MDMA versus 30mg MDMA active placebo in the remaining 12 participants. The 30mg MDMA active placebo is not expected to provide therapeutic benefits and is aimed at ensuring an effective blind by producing some physiological effects.

Those randomised to receive the full dose in Stage 1 will receive two drug-assisted psychotherapy sessions and 10 non-drug psychotherapy sessions of exactly the same duration and sequence as those in the lead-in.

Those randomised to receive the active placebo in Stage 1 will receive two drug-assisted (active placebo) psychotherapy sessions using 30mg MDMA with an optional supplemental dose of 15mg MDMA (cumulative dose 45mg) and 10 non-drug psychotherapy sessions. The session duration and the sequence of the 12 sessions will be exactly the same as those in the lead-in.

Stage 2 is an optional treatment for those participants (only) who received the active placebo in Stage 1. After unblinding at the end of Stage 1, eligible participants who choose to complete Stage 2 will undergo an open label full dose treatment involving two drug-assisted psychotherapy sessions and eight non-drug psychotherapy sessions. The session durations will be the same as for the lead-in. The session sequence for Stage 2 is as follows.

Session 1: Non-drug preparatory psychotherapy.
Session 2: Experimental drug-assisted psychotherapy.
Sessions 3,4,5: Non-drug integrative psychotherapy.
Session 6: Experimental drug-assisted psychotherapy.
Sessions 7,8,9: Non-drug integrative psychotherapy.
Session 10: Non-drug follow-up psychotherapy.

All study participants will attend an additional long term follow-up session 12 months after their final experimental drug-assisted session.
Intervention code [1] 284287 0
Treatment: Drugs
Comparator / control treatment
Drug: 3,4-methylenedioxymethamphetamine (MDMA) 30mg followed 2.5 hours later by 15mg as a low-level active placebo with no anticipated therapeutic value, administered as capsules in conjunction with manualised psychotherapy. The low-level active placebo is necessary to ensure effective blinding by inducing some physiological effects of the drug in participants. This is not a dose comparison study.

The active placebo will be administered during two drug-assisted psychotherapy sessions which occur as the fourth and eighth sessions in a 12 session treatment. The remaining 10 sessions involve non-drug psychotherapy only.
Control group
Placebo

Outcomes
Primary outcome [1] 286539 0
Changes in PTSD symptoms as measured via Global Clinician-Administered PTSD Scale (CAPS) scores.
Timepoint [1] 286539 0
At baseline, at the end of Stage 1 and at the end of Stage 2. At 12 month long term follow up.
Secondary outcome [1] 296115 0
Assess depression symptoms via the Beck Depression Inventory-II (BDI-II).
Timepoint [1] 296115 0
At baseline, at the end of Stage 1 and at the end of Stage 2. At 12 month long term follow up.
Secondary outcome [2] 296116 0
Assess quality of life via the Global Assessment of Functionality (GAF).
Timepoint [2] 296116 0
At baseline, at the end of Stage 1 and at the end of Stage 2. At 12 month long term follow up.
Secondary outcome [3] 296117 0
Assess self-reported sleep quality via the Pittsburgh Sleep Quality Index (PSQI).
Timepoint [3] 296117 0
At baseline, at the end of Stage 1 and at the end of Stage 2. At 12 month long term follow up.
Secondary outcome [4] 296118 0
Assess general well-being via the WHO Quality of Life Assessment (WHOQOL-BREF).
Timepoint [4] 296118 0
At baseline, at the end of Stage 1 and at the end of Stage 2. At 12 month long term follow up.
Secondary outcome [5] 296119 0
PTSD Diagnostic Scale (PDS)
Timepoint [5] 296119 0
At baseline, during the third integrative session after each experimental session, at the end of Stage 1 and the end of Stage 2. At 12 month long term follow up.

Eligibility
Key inclusion criteria
1. Meet DSM-IV criteria for chronic PTSD with a duration of at least six months.
2. Have a CAPS score of 50 or higher, indicating moderate to severe PTSD symptoms.
3. Have had at least one unsuccessful attempt at treatment for PTSD using drugs (SSRI, SNRI or MAOI) and/or psychotherapy; OR who discontinued treatment due to either: inability to tolerate psychotherapy for PTSD, or inability to tolerate psychopharmacology for PTSD due to treatment emergent side effects.
4. May have a concurrent affective disorder, excepting bipolar affective disorder 1.
5. Are war veterans.
6. If female and of childbearing potential, must have negative pregnancy test results, be willing to have pregnancy tests and must agree to use an effective form of birth control during throughout the treatment period.
7. Are proficient in speaking and reading English.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Are pregnant or nursing, or of child bearing potential and not practising an effective method of birth control.
2. Have a personal or immediate family history of or current primary psychotic disorder, bipolar affective disorder type 1, or borderline personality disorder.
3. Are diagnosed with dissociative identity disorder or an eating disorder with active purging.
4.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 (participants with hypothyroidism who are on adequate and stable thyroid replacement will not be excluded).
5. Have hypertension using the standard criteria of the American Heart Association (values of 140/90 or higher assessed on three separate occasions) unless their hypertension has been successfully treated and is currently well-controlled on antihypertensive medicines. In this case participants with well-controlled hypertension may be enrolled if they pass additional screening to rule out underlying cardiovascular disease.
6. Have liver disease.
7. Have a history of Diabetes Type I or II.
8. Have a history of hyponatraemia or hyperthermia.
9. Weigh less than 48 kg.
10. Would present a serious suicide risk or who are likely to require hospitalisation during the course of the study.
11. Have used “Ecstasy” (material represented as containing MDMA) more than five times in the past 3 years or at any time within 6 months of the MDMA session.
12. Require ongoing concomitant therapy with a psychiatric drug, including but not limited to SSRIs, SNRIs, or MAOIs.
13. Meet DSM-IV criteria for substance abuse or dependence for any substance save caffeine or nicotine in the past 60 days.
14. Have glaucoma, significant atherosclerosis or hyperthyroidism.
15. Have any current problem, which in the opinion of the investigator or medical
monitor, might interfere with participation in 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)
The research staff will determine eligibility and enrol subjects to the study groups. The first two participants will be enrolled in the open-label lead-in and assigned to the full dose condition. The subsequent 12 participants will be enrolled in the randomised Stage 1. The randomised portion of the study will be double-blinded. An unblinded randomisation monitor will generate the randomisation list. Participants will be assigned participant numbers consecutively, and participants will be randomised in a blinded fashion. Upon enroling a participant, the investigator will be provided with an Enrolment Code for that participant. Randomisation numbers will be pre-printed on the container labels corresponding to doses for individual sessions. The therapists will utilise a web-based randomisation program to obtain the container assignment for each experimental session. Blinded personnel will conduct all study evaluations in the randomised portion of the study until the blind is broken for each participant at the end of Stage 1.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Web-based computer randomisation program.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
The first two participants enrolled in the trial will be assigned to the open label lead-in and will receive full dose MDMA-assisted psychotherapy treatment.

The remaining 12 participants will be randomised to the Stage 1 double-blind arm, comparing 125mg MDMA with 30mg MDMA active placebo during MDMA-assisted psychotherapy treatment.

In Stage 2, only participants who received the active placebo dose during Stage 1 may volunteer for assignment to an open label full dose MDMA-assisted psychotherapy treatment.
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
2/09/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
14
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 284724 0
Charities/Societies/Foundations
Name [1] 284724 0
Psychedelic Research in Science & Medicine Inc
Country [1] 284724 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Psychedelic Research in Science & Medicine Inc
Address
PO Box 72
Balwyn North Vic 3104
Country
Australia
Secondary sponsor category [1] 283622 0
Charities/Societies/Foundations
Name [1] 283622 0
Multidisciplinary Association for Psychedelic Studies
Address [1] 283622 0
309 Cedar Street #2323
Santa Cruz, CA 95060
Country [1] 283622 0
United States of America

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 286732 0
Bellberry Limited
Ethics committee address [1] 286732 0
Ethics committee country [1] 286732 0
Australia
Date submitted for ethics approval [1] 286732 0
09/02/2012
Approval date [1] 286732 0
Ethics approval number [1] 286732 0
2011-12-607

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33789 0
Dr Stuart Saker MBBS
Address 33789 0
The Bankstown Clinic
Level 1, 107 Bankstown City Plaza
Bankstown NSW 2200
Country 33789 0
Australia
Phone 33789 0
+61 2 9705 0305
Fax 33789 0
Email 33789 0
stuart.saker@unsw.edu.au
Contact person for public queries
Name 17036 0
Steve McDonald
Address 17036 0
Association Secretary
Psychedelic Research in Science & Medicine Inc (PRISM)
PO Box 72
Balwyn North Vic 3104
Country 17036 0
Australia
Phone 17036 0
+61 409 633 659
Fax 17036 0
Email 17036 0
stevemc@prism.org.au
Contact person for scientific queries
Name 7964 0
Martin Williams PhD
Address 7964 0
President
Psychedelic Research in Science & Medicine Inc (PRISM) PO Box 72 Balwyn North Vic 3104
Country 7964 0
Australia
Phone 7964 0
+61 419 678 918
Fax 7964 0
Email 7964 0
martin@prism.org.au

No information has been provided regarding IPD availability


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.