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Trial registered on ANZCTR


Registration number
ACTRN12624000871549
Ethics application status
Approved
Date submitted
23/05/2024
Date registered
16/07/2024
Date last updated
16/07/2024
Date data sharing statement initially provided
16/07/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Pilot investigation of psychedelic-assisted psychotherapy for treatment of post-traumatic stress disorder (PTSD) in people diagnosed with co-occurring borderline personality disorder – a controlled before-and-after study
Scientific title
Pilot investigation of psychedelic-assisted psychotherapy for treatment of post-traumatic stress disorder (PTSD) in people diagnosed with co-occurring borderline personality disorder – a controlled before-and-after study
Secondary ID [1] 312205 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
borderline personality disorder (BPD) 333882 0
post-traumatic stress disorder (PTSD) 333884 0
Condition category
Condition code
Mental Health 330559 330559 0 0
Psychosis and personality disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A treatment that combines BPD-specific psychotherapy and 3,4-Methylenedioxymethamphetamine (MDMA) within the public mental health sector.

The initial recruitment effort will focus on identifying participants for the MDMA treatment arm. Once MDMA treatment arm participants have commenced treatment, recruitment will target psychotherapy-only participants who will be matched on sex, age (within 2 years), education, and similarity in clinical presentation. The comparator participants will receive the same psychological treatment without the MDMA sessions.

Following comprehensive assessment, all participants will participate in a pre-treatment module. This comprises one-hour individual psychotherapy sessions each week for six weeks which provide psychoeducation about PTSD and BPD, describe the course of treatment, role of the clinician, expectations of participants, likely challenges that will arise, co-development of treatment and crisis plans, and (if they are in the MDMA arm) preparatory sessions prior to the first administration of MDMA. The psychotherapy approach that will be used is ‘Good’ or ‘General Psychiatric Management’ (GPM), which has been shown in a large randomized control trial to be as efficacious as Dialectical Behavior Therapy (DBT) across different outcomes such as reducing symptomatic distress, suicidal behaviour, utilisation of disability benefits, and overall BPD pathology. This generalist psychotherapy approach to managing BPD is able to be individualised and is flexible in its application for patients who experience severe presentations of BPD.

For participants in the MDMA arm, between two and five MDMA sessions will be offered during a six-month course of GPM-Complex with at least one-month intervals between the sessions. According to the patient's response to MDMA and the psychiatrist's clinical judgement, the psychiatrist will decide on the number of MDMA sessions (two, three, four or five sessions). MDMA treatment sessions will last for up to eight hours. The starting dose for the first session will be 80mg, with a possible additional dose of 40mg as clinically indicated. Depending on each participant’s response to MDMA, the dosing schedule may vary in subsequent sessions. Blood pressure and heart rate will be measured at 1.5 to 2 hours after the initial dose. A session checklist will be used to record the adherence to the intervention components.

MDMA treatment sessions will take place in a dedicated space staffed with two therapists – one male and one female. One will be the principal therapist (a psychiatrist) who will prescribe the MDMA, and the other will be the co-therapist, an experienced DBT clinician. Both will be familiar to participants from previous treatment sessions. Informed consent will be requested prior to each MDMA session. MDMA in the form of an oral tablet will be administered at the beginning of the session. All sessions will be videotaped for review (if required) in case of conflict resolution or clinical supervision. The content of MDMA sessions will be guided by the participant rather than directed by the therapist. Therapists will provide an empathetic, safe, and validating environment to assist the participant in processing traumatic experiences. Therapists are able to provide more active support as needed.

Post-MDMA treatment sessions will continue weekly, focusing on integration of experiences arising from the MDMA session(s) using a GPM-Complex approach. The integration process helps the participant with meaning-making, creating awareness, and translating insights that the participant experienced during the MDMA treatment session. The comparator group will continue receiving one-hour weekly GPM-Complex sessions for six months. Apart from the integration sessions, the structure and content of GPM-Complex will be similar for participants in both treatment arms. The key study outcomes will be evaluated during and after six months for participants in both arms. Some evaluation instruments will be completed again at three and six months’ post-discharge. In the case that participants continue in treatment for an additional six months (DBT psychotherapy will be offered if clinically indicated), outcomes will continue to be measured after three and six months of DBT and then at three and six months’ post-treatment.

If at the end of six-month study period, further treatment is indicated for participants in either treatment arm, they will be offered an additional six months of dialectical behavior therapy (DBT) – the most widely used specialist manualised treatment for BPD. As a specialist public mental health service, Spectrum’s purpose is to support clients to meet their treatment goals. This usually entails achieving clinical remission from symptoms of BPD.

Two of Spectrum’s doctors (psychiatrists) have completed the specialist MDMA training (MAPS19) and have appropriate qualifications to prescribe MDMA. Several female DBT-trained Spectrum clinicians will be trained in-house to assist the study doctors with the MDMA psychological treatment sessions as co-therapists will be present for the pre-MDMA preparation sessions, during MDMA treatment days, at post-MDMA integration sessions, and available to facilitating regular psychotherapy sessions when the study doctors are unavailable. If required, the co-therapists will also facilitate the additional six months of psychological treatment using DBT once the 6 month study period has ended. Spectrum’s medical team will conduct all clinical assessments. Spectrum’s research team (led by study investigator) will oversee completion of the evaluation measures.
Intervention code [1] 328652 0
Treatment: Drugs
Intervention code [2] 328759 0
Treatment: Other
Comparator / control treatment
The comparator participants will receive BPD-specific psychotherapy without the MDMA sessions.
The psychotherapy approach that will be used is ‘Good’ or ‘General Psychiatric Management’ (GPM), which has been shown in a large randomized control trial to be as efficacious as Dialectical Behavior Therapy (DBT) across different outcomes such as reducing symptomatic distress, suicidal behaviour, utilisation of disability benefits, and overall BPD pathology. This generalist psychotherapy approach to managing BPD is able to be individualised and is flexible in its application for patients who experience severe presentations of BPD.

GPM is a therapeutic approach that helps patients with BPD manage their emotions and behaviours. It focuses on understanding how patients' hypersensitivity to relationship stressors impacts their emotions and behaviours.
GPM emphasizes the importance of relationships and how they can be a source of both stress and support. Therapists work with patients to identify and manage relationship stressors, improve communication skills, and build healthier relationships.

GPM incorporates practical tools and strategies such as problem-solving, education, and goal-setting to help patients manage their symptoms and improve their overall functioning
Control group
Active

Outcomes
Primary outcome [1] 338314 0
Safety
Timepoint [1] 338314 0
Adverse events will be assessed at every session throughout the 6 to 12-month intervention
Primary outcome [2] 338315 0
Feasibility from the perspectives of Spectrum clinicians
Timepoint [2] 338315 0
Feasibility will be assessed at every session throughout the 6 to 12-month intervention
Primary outcome [3] 338316 0
Cost
Timepoint [3] 338316 0
At the end of the intervention when the treatment arm completed the treatment course
Secondary outcome [1] 435403 0
State of mood
Timepoint [1] 435403 0
Two month intervals from admission to discharge; 3 and 6 months post-discharge
Secondary outcome [2] 435404 0
Dissociation
Timepoint [2] 435404 0
Two month intervals from admission to discharge; 3 and 6 months post-discharge
Secondary outcome [3] 435405 0
Dissociative symptoms
Timepoint [3] 435405 0
Two month intervals from admission to discharge; 3 and 6 months post-discharge
Secondary outcome [4] 435406 0
DSM-5 criteria for PTSD
Timepoint [4] 435406 0
Admission and discharge
Secondary outcome [5] 435407 0
Symptoms of PTSD
Timepoint [5] 435407 0
Admission and discharge; 3 and 6 months post-discharge
Secondary outcome [6] 435408 0
Composite core features of Post-Traumatic Stress Disorder (PTSD) and Complex PTSD (CPTSD)
Timepoint [6] 435408 0
Admission and discharge; 3 and 6 months post-discharge
Secondary outcome [7] 435409 0
Borderline Symptoms
Timepoint [7] 435409 0
Two-month intervals from admission to discharge; 3 and 6 months post-discharge
Secondary outcome [8] 435410 0
Self-compassion
Timepoint [8] 435410 0
Two-month intervals from admission to discharge; 3 and 6 months post-discharge
Secondary outcome [9] 435411 0
A composite measure for Suicidality/self-harm ideation/behaviours
Timepoint [9] 435411 0
Two-month intervals from admission to discharge; 3 and 6 months post-discharge
Secondary outcome [10] 435412 0
A composite measure for state guilt and shame
Timepoint [10] 435412 0
Two-month intervals from admission to discharge; 3 and 6 months post-discharge
Secondary outcome [11] 435413 0
Clinical review checklist completed by the principal therapist that includes a validated single-item psychiatric rating instrument for quantifying serial change during the course of clinical trials
Timepoint [11] 435413 0
Fortnightly while engaged in treatment
Secondary outcome [12] 435414 0
How participants' condition has changed
Timepoint [12] 435414 0
Fortnightly while engaged in treatment
Secondary outcome [13] 435415 0
A composite measure assessing the three key aspects of the therapeutic alliance: (a) agreement on the tasks of therapy, (b) agreement on the goals of therapy and (c) development of an affective bond
Timepoint [13] 435415 0
Monthly while engaged in treatment
Secondary outcome [14] 435416 0
Clinical supervisors' perceptions of therapist countertransference behaviour in a given session
Timepoint [14] 435416 0
Following MDMA sessions
Secondary outcome [15] 435417 0
Quality of life of people with different mental health conditions, focusing on the process of recovery for people using mental health services
Timepoint [15] 435417 0
Monthly from admission to discharge; 3 and 6 months post-discharge
Secondary outcome [16] 435418 0
Acceptability of a healthcare intervention
Timepoint [16] 435418 0
Monthly while engaged in treatment (and after MDMA sessions)
Secondary outcome [17] 435419 0
Suicidality
Timepoint [17] 435419 0
Monthly while engaged in treatment (and after MDMA sessions)
Secondary outcome [18] 435420 0
Treatment Engagement
Timepoint [18] 435420 0
Monthly while engaged in treatment
Secondary outcome [19] 435421 0
Acute psychologically insightful experiences that may occur during exposure to psychedelic medication
Timepoint [19] 435421 0
Following MDMA sessions
Secondary outcome [20] 436277 0
Feasibility from the perspectives of Spectrum clients (This is a primary outcome)
Timepoint [20] 436277 0
Feasibility will be assessed at every session throughout the 6 to 12-month intervention

Eligibility
Key inclusion criteria
• Female clients aged 18 years or older who are eligible for treatment from Spectrum’s Complex Care Team (reserved for clients with severe and high risk presentations for whom manualised specialised treatment programs are not indicated)
• Diagnosis of PTSD (or Complex PTSD)
• Diagnosis of BPD
• Effective method of contraception if of child-bearing age
• Fluent in written and spoken English language
Minimum age
18 Years
Maximum age
90 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
• Diagnosis of Narcissistic or Antisocial Personality Disorder (which lack the attachment pathology we believe is amenable to the actions of MDMA)
• Diagnosis or likely diagnosis of Autism Spectrum Disorder or traits
• Currently taking prescription medication for attention deficit hyperactivity disorder (ADHD)
• Intellectual disability severe enough to affect the provision of informed consent and preclude engagement in psychological treatment programs
• Serious medical illness (particularly those affecting the cardiovascular system)
• Pregnant or breast-feeding
• Medication prescribed to treat psychiatric symptoms. Contraindicated substances and medications include MDMA metabolites or analogues, anaesthetics, muscle relaxants, amphetamines and stimulants, benzodiazepines, ethanol, opioids, antidepressants (e.g. bupropion, sertraline, venlafaxine, moclobemide, and citalopram), olanzapine and any medication that increases the concentration of serotonin. Study participation will require cessation of these medications prior to commencing the study.22 In practice, a washout period will be required, generally two weeks for most psychotropic medications. The tapering and ceasing will only be initiated when a MDMA dosing date is determined and then the tapering start will be backdated from this. It is possible that a participant's symptoms will worsen during this tapering and ceasing phase. Cessation of medication will be carried out under clinical supervision where it is considered safe to do so. The decision to cease medications will be for the participant and their usual treating practitioner to determine.

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
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
26/07/2024
Actual
Date of last participant enrolment
Anticipated
25/07/2025
Actual
Date of last data collection
Anticipated
26/06/2026
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 42612 0
3121 - Richmond

Funding & Sponsors
Funding source category [1] 316581 0
Other
Name [1] 316581 0
Spectrum Personality Disorder Service for Victoria
Country [1] 316581 0
Australia
Primary sponsor type
Other
Name
Spectrum Personality Disorder Service for Victoria
Address
Country
Australia
Secondary sponsor category [1] 318761 0
None
Name [1] 318761 0
Address [1] 318761 0
Country [1] 318761 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315369 0
Eastern Health Human Research Ethics Committee
Ethics committee address [1] 315369 0
Ethics committee country [1] 315369 0
Australia
Date submitted for ethics approval [1] 315369 0
28/11/2023
Approval date [1] 315369 0
27/03/2024
Ethics approval number [1] 315369 0
E23-013-102057

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

Contacts
Principal investigator
Name 134482 0
A/Prof Sathya Rao
Address 134482 0
Spectrum - Personality Disorder and Complex Trauma Service, Eastern Health, 110 Church Street, Richmond, VIC 3121
Country 134482 0
Australia
Phone 134482 0
+61 417560979
Fax 134482 0
Email 134482 0
sathya.rao@easternhealth.org.au
Contact person for public queries
Name 134483 0
A/Prof Jillian Broadbear
Address 134483 0
Spectrum - Personality Disorder and Complex Trauma Service, Eastern Health, 110 Church Street, Richmond, VIC 3121
Country 134483 0
Australia
Phone 134483 0
+61 3 8413 8674
Fax 134483 0
Email 134483 0
jillian.broadbear@easternhealth.org.au
Contact person for scientific queries
Name 134484 0
A/Prof Jillian Broadbear
Address 134484 0
Spectrum - Personality Disorder and Complex Trauma Service, Eastern Health, 110 Church Street, Richmond, VIC 3121
Country 134484 0
Australia
Phone 134484 0
+61 3 8413 8674
Fax 134484 0
Email 134484 0
jillian.broadbear@easternhealth.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The whole psychotherapy will be tape-recorded, so the researchers have decided to make the data confidential at this stage.


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.