Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000041550
Ethics application status
Approved
Date submitted
13/11/2023
Date registered
17/01/2024
Date last updated
17/01/2024
Date data sharing statement initially provided
17/01/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effectiveness Of Psychedelic Therapy for Post Traumatic Stress Disorder (PTSD)
Scientific title
Effectiveness Of Psychedelic Therapy for Post Traumatic Stress Disorder (PTSD)
Secondary ID [1] 310948 0
Nil Known
Universal Trial Number (UTN)
U1111-1300-3340
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post Traumatic Stress Disorder (PTSD) 332025 0
Condition category
Condition code
Mental Health 328756 328756 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
MDMA medicines are given orally in a capsule form once in the morning on the medicine days only. The medicine dosing is by the treating psychiatrist, and he will ensure the patient has swallowed the medicine at dosing. No other strategies are available or indicated. The medicines used are Methylenedioxy methamphetamine (MDMA) for PTSD.
Medicine days occur 2-3 times (depending on response to treatment) interspersed with psychotherapy for all arms of treatment:
ie for all arms: 3 Preparatory sessions/1 Medicine Day/3 Integration Sessions 1 week apart/ 1 Medicine Day/ 3 Integration Sessions 1 week apart/ Then an optional 3rd Medicine Day and 3 Integration Sessions 1 week apart, if there's an inadequate response to treatment
The usual dose of MDMA for arms 1 and 2, will be 120mg with 60mg top up 2 hours later as per the MAPS studies. The 80mg with 40mg top up will be if the higher dose option is not tolerated. If the patient is quite anxious we may dose the first medicine day at 80mg plus 40mg top up. Then move to 120mg plus 60mg top up for subsequent sessions.
Arm 1 active : MDMA (80-120mg + 40-60mg top up) given once in morning on 2-3 medicine days only through the treatment interspersed with usual supportive psychotherapy (as detailed below).
Arm 2 active : MDMA (80-120mg + 40-60mg) given once in morning on 2-3 medicine days through the treatment interspersed with psychotherapy where 1 of each of the 3 Integration Sessions is a specialised EMDR (eye movement desesitisation and reprocessing) session; with the other 2 sessions being usual supportive psychotherapy
Psychotherapy (all sessions are 1 hour)
• Three preparation sessions held approximately a week apart.
Dr Ranil Gunewardene will conduct the first preparation session 1:1 in rooms or via Zoom for 60 minutes. During this session, further in depth assessment will take place and medical review.

The second and third preparation session will be with a HREC approved Psychologist/ psychotherapist 1:1 either in rooms or via Zoom for 1 hour each.

• One Dosing session ( approximately 6-7 hours face to face) where supportive, client centered psychotherapy is provided during the dosing experience at Northern Beaches Hospital Clinic Rooms. Psychiatrist Dr Ranil Gunewardene will conduct the administration of medicine, regular monitoring and medical supervision of the client. Dr Ranil Gunewardene will provide direct client time face to face as clinically required. The designated treating HREC approved Psychologist/ Psychotherapist will work face to face with the client throughout their dosing day providing client centered psychotherapy.

• Three Integration sessions conducted 1:1 by HREC approved the psychologist/ psychotherapist with the first one held the day after the dosing session and then held approximately a week apart.

• In Arm 2 one of the 3 Integration Sessions will be EMDR. All other psychotherapy sessions, including all sessions for Arms 1, will be as detailed as per the supportive model below
Who:
HREC approved Psychologists/Psychotherapists conducting the preparation sessions, dosing and integration therapy sessions are all fully registered and have additional training in psychedelic assisted therapy.

Mode of Administration:
Preparation and Integration sessions will be 1:1 with a psychologist/ psychotherapist or psychiatrist and will be offered either face to face or via Zoom for 60 minutes.
Monitoring:
• The treatment dyad consisting of Dr Ranil Gunewardene and one of the HREC approved PAT trained psychologists/psychotherapists will be consistent across the course of the treatment and will ensure follow up any non attendance at appointments with telephone contact from the clinic to support adherence to the full therapy program.
• A spreadsheet that records client dates of sessions and disengagement from the therapy program prior to completion will be recorded along with action taken to re-engage the client.
• Adverse Events will be recorded and reported to HREC and TGA
• Pre and post psychometric measures will be administered.

Psychedelic Assisted Psychotherapy for both MDMA and Psilocybin is taught during Psychedelic Assisted Therapy training programs that have been completed by all of the psychologists/psychotherapists and the psychiatrist delivering the service.
In Summary the therapy approach for all sessions is simply supportive psychotherapy based. There is psychoeducation delivered and set setting and relationship building is undertaken. The therapist is encouraged to stay out of the way of the patient’s medicine guided realisations and perspective shifts. To be guided by the patient’s experiences not the therapist’s agenda. To encourage the rediscovering of the wiser self and to promote patient agency. The therapist is there to support the patient rediscovering and connecting to their “inner healing intelligence”. There are principles of emotional support, encouragement, validation of experiences and perspectives, exploration of feeling states, in a non directive and non judgmental therapist stance.

EMDR as one of the Integration Sessions in Arm 2
The two EMDR sessions will be delivered as one of the group of 3 post dosing integration sessions in Arm 2 only. Ie 1 EMDR session per block of 3 integration sessions.
The EMDR sessions will be held 1:1 in face to face 60 minute sessions. All psychologists/ psychotherapists have been trained in EMDR and are experienced with this treatment model.
The first EMDR session involves a brief explanation of EMDR treatment model and methods. The therapist then identifies the target memory or experience that is central to the trauma. The associated image, negative cognition, body sensation and emotion are then identified and the client provides a subjective rating of distress out of 10. Multiple sets of Bilateral Stimulation (usually eye movement where the client tracks the hand movement of the therapist) that last 30 -120 seconds, with breaks for brief check in and minimal prompts by the therapist if required. The distress rating is reviewed and if it is zero on three occasions, then a positive cognition is installed using further Bilateral Stimulation. The session is then reviewed and concludes.
The second session will begin with a review of the previous session and client experience in between sessions. The target memory is reviewed with the associated image, negative cognition, body sensation and emotion and the level of distress rated out of 10. Further BLS is conducted and the distress rating is reviewed and if it is zero on three occasions, then a positive cognition is installed using further Bilateral Stimulation.
Intervention code [1] 327380 0
Treatment: Drugs
Intervention code [2] 327381 0
Treatment: Other
Comparator / control treatment
MDMA medicines are given orally in a capsule form once in the morning on the medicine days only. The medicine dosing is by the treating psychiatrist, and he will ensure the patient has swallowed the medicine at dosing. No other strategies are available or indicated. The medicines used are Methylenedioxy methamphetamine (MDMA) for PTSD.
Medicine days occur 2-3 times (depending on response to treatment) interspersed with psychotherapy for all arms of treatment:
ie for all arms: 3 Preparatory sessions/1 Medicine Day/3 Integration Sessions 1 week apart/ 1 Medicine Day/ 3 Integration Sessions 1 week apart/ Then an optional 3rd Medicine Day and 3 Integration Sessions 1 week apart, if there's an inadequate response to treatment
The usual dose of MDMA for arms 1 and 2, will be 120mg with 60mg top up 2 hours later as per the MAPS studies. The 80mg with 40mg top up will be if the higher dose option is not tolerated. If the patient is quite anxious we may dose the first medicine day at 80mg plus 40mg top up. Then move to 120mg plus 60mg top up for subsequent sessions.

Arm 1 active : MDMA (80-120mg + 40-60mg top up) given once in morning on 2-3 medicine days only through the treatment interspersed with usual supportive psychotherapy (as detailed below).

Psychotherapy (all sessions are 1 hour)
• Three preparation sessions held approximately a week apart.
Dr Ranil Gunewardene will conduct the first preparation session 1:1 in rooms or via Zoom for 60 minutes. During this session, further in depth assessment will take place and medical review.

The second and third preparation session will be with a HREC approved Psychologist/ psychotherapist 1:1 either in rooms or via Zoom for 1 hour each.

• One Dosing session ( approximately 6-7 hours face to face) where supportive, client centered psychotherapy is provided during the dosing experience at Northern Beaches Hospital Clinic Rooms. Psychiatrist Dr Ranil Gunewardene will conduct the administration of medicine, regular monitoring and medical supervision of the client. Dr Ranil Gunewardene will provide direct client time face to face as clinically required. The designated treating HREC approved Psychologist/ Psychotherapist will work face to face with the client throughout their dosing day providing client centered psychotherapy.

• Three Integration sessions conducted 1:1 by HREC approved the psychologist/ psychotherapist with the first one held the day after the dosing session and then held approximately a week apart.

Who:
HREC approved Psychologists/Psychotherapists conducting the preparation sessions, dosing and integration therapy sessions are all fully registered and have additional training in psychedelic assisted therapy.

Mode of Administration:
Preparation and Integration sessions will be 1:1 with a psychologist/ psychotherapist or psychiatrist and will be offered either face to face or via Zoom for 60 minutes.
Monitoring:
• The treatment dyad consisting of Dr Ranil Gunewardene and one of the HREC approved PAT trained psychologists/psychotherapists will be consistent across the course of the treatment and will ensure follow up any non attendance at appointments with telephone contact from the clinic to support adherence to the full therapy program.
• A spreadsheet that records client dates of sessions and disengagement from the therapy program prior to completion will be recorded along with action taken to re-engage the client.
• Adverse Events will be recorded and reported to HREC and TGA
• Pre and post psychometric measures will be administered.

Psychedelic Assisted Psychotherapy for both MDMA and Psilocybin is taught during Psychedelic Assisted Therapy training programs that have been completed by all of the psychologists/psychotherapists and the psychiatrist delivering the service.
In Summary the therapy approach for all sessions is simply supportive psychotherapy based. There is psychoeducation delivered and set setting and relationship building is undertaken. The therapist is encouraged to stay out of the way of the patient’s medicine guided realisations and perspective shifts. To be guided by the patient’s experiences not the therapist’s agenda. To encourage the rediscovering of the wiser self and to promote patient agency. The therapist is there to support the patient rediscovering and connecting to their “inner healing intelligence”. There are principles of emotional support, encouragement, validation of experiences and perspectives, exploration of feeling states, in a non directive and non judgmental therapist stance.


Control group
Active

Outcomes
Primary outcome [1] 336811 0
Change in clinican rated PTSD symptoms from baseline
Timepoint [1] 336811 0
Baseline and 2 weeks after treatment completed
Secondary outcome [1] 428824 0
Change in PTSD symptoms from baseline
Timepoint [1] 428824 0
At baseline and 2 weeks after therapy completed
Secondary outcome [2] 429343 0
Change in trauma from baseline
Timepoint [2] 429343 0
At baseline and 2 weeks after therapy completed
Secondary outcome [3] 429734 0
Change in adverse events from baseline
Timepoint [3] 429734 0
Baseline and 2 weeks post treatment
Secondary outcome [4] 429735 0
Change in personality disorder symptoms from baseline
Timepoint [4] 429735 0
Baseline and 2 weeks post treatment
Secondary outcome [5] 429736 0
Change in disability
Timepoint [5] 429736 0
baseline and 2 weeks post treatment
Secondary outcome [6] 429737 0
Change in connection from baseline
Timepoint [6] 429737 0
Baseline and 2 weeks post treatment
Secondary outcome [7] 429738 0
Change in relationships from baseline
Timepoint [7] 429738 0
Baseline and 2 weeks post treatment
Secondary outcome [8] 430200 0
Change in mystical experiences from baseline
Timepoint [8] 430200 0
Baseline and 2 weeks post treatment
Secondary outcome [9] 430201 0
Change in alcohol use from baseline
Timepoint [9] 430201 0
Baseline and 2 weeks post treatment
Secondary outcome [10] 430202 0
Change in drug use from baseline
Timepoint [10] 430202 0
Baseline and 2 weeks post treatment
Secondary outcome [11] 430203 0
Change in suicidal ideation from baseline
Timepoint [11] 430203 0
Baseline and 2 weeks post treatment
Secondary outcome [12] 430204 0
Change in clinician rated depression from baseline
Timepoint [12] 430204 0
Baseline and 2 weeks post treatment
Secondary outcome [13] 430205 0
Change in depression
Timepoint [13] 430205 0
Baseline and 2 weeks post treatment
Secondary outcome [14] 430779 0
Change in eating attitudes from baseline [Substudy for patients with symptoms of an eating disorder]
Timepoint [14] 430779 0
baseline and 2 weeks post treatment
Secondary outcome [15] 430780 0
Change in disordered eating from baseline [Substudy for patients with symptoms of an eating disorder]
Timepoint [15] 430780 0
baseline and 2 weeks post treatment
Secondary outcome [16] 430781 0
Change in eating disorder symptomology from baseline [Substudy for patients with symptoms of an eating disorder]
Timepoint [16] 430781 0
baseline and 2 weeks post treatment

Eligibility
Key inclusion criteria
Must suffer from: Post Traumatic Stress Disorder
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) Is not able to give adequate informed consent, or is under 18 or over 65 years old.
(2) Has uncontrolled hypertension or unstable diabetes.
(3) Has a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds [ms] corrected by Bazett's formula)1
(4) Has a history of additional risk factors for Torsade de pointes (e.g. heart failure, hypokalemia, family history of Long QT Syndrome).
(5) Has evidence or history of significant medical disorders e.g. epilepsy, stroke, unstable cardio vascular disease
(6) Has symptomatic liver disease.
(7) Has a history of hyponatremia or hyperthermia.
(8) Weighs less than 48 kg.
(9) Is pregnant or nursing or is of childbearing age and is not practicing an effective means of birth control.
10) Is currently abusing illegal drugs

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)
We will use and online randomiser to fairly allocate patients to one of 2 active arms: 1) Control: MDMA with usual supportive psychotherapy only 2) MDMA with mainly supportive psychotherapy but where 1 of the 3 integration session groups is an EMDR session. The rest of the sessions are supportive only
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
online computer generated randomiser
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
4/12/2023
Date of last participant enrolment
Anticipated
18/12/2028
Actual
Date of last data collection
Anticipated
5/01/2029
Actual
Sample size
Target
30
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 315208 0
Self funded/Unfunded
Name [1] 315208 0
Patients are self funded or may be funded by an organisation eg an Insurance company Armed Forces Department of Veterans Affairs etc
Country [1] 315208 0
Primary sponsor type
Individual
Name
Dr and A/ Professor Ranil Gunewardene
Address
Northern Beaches Hospital Mindlife Clinic Suite 18 Level 7, 105 Frenchs Forest Rd West Frenchs Forest NSW 2086
Country
Australia
Secondary sponsor category [1] 317241 0
None
Name [1] 317241 0
Address [1] 317241 0
Country [1] 317241 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314133 0
Townsville Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 314133 0
100 Angus Smith Drive Douglas QLD 4814
Ethics committee country [1] 314133 0
Australia
Date submitted for ethics approval [1] 314133 0
16/10/2023
Approval date [1] 314133 0
08/11/2023
Ethics approval number [1] 314133 0
HREC/2023/QTHS/103245

Summary
Brief summary
We intend to measure the effectiveness of psychedelic assisted medicines (methylene dioxy methamphetamine - MDMA) when combined with talking therapy; for the treatment of Post Traumatic Stress Disorder in real world patient groups

We will test how effective MDMA is for PTSD and treat patients who have had limited benefits with existing treatments for these hard to treat conditions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 130530 0
A/Prof Dr Ranil Gunewardene
Address 130530 0
Mindlife Clinic Northern Beaches Hospital Suite 18, Level 7, 105 Frenchs Forest Rd West Frenchs Forest NSW 2086
Country 130530 0
Australia
Phone 130530 0
+61 0466534211
Fax 130530 0
Email 130530 0
ranil0001@yahoo.com.au
Contact person for public queries
Name 130531 0
Ms Kitrina Heathcoate
Address 130531 0
Mindlife Clinic Northern Beaches Hospital Suite 18, Level 7, 105 Frenchs Forest Rd West Frenchs Forest NSW 2086
Country 130531 0
Australia
Phone 130531 0
+61 0424292306
Fax 130531 0
Email 130531 0
reception@mindlifeclinic.com
Contact person for scientific queries
Name 130532 0
Dr Ranil Gunewardene
Address 130532 0
Mindlife Clinic Northern Beaches Hospital Suite 18, Level 7, 105 Frenchs Forest Rd West Frenchs Forest NSW 2086
Country 130532 0
Australia
Phone 130532 0
+61 0466534211
Fax 130532 0
Email 130532 0
ranil0001@yahoo.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data is grouped into assessment scale scores for all patients


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.