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Trial registered on ANZCTR


Registration number
ACTRN12623000832673
Ethics application status
Approved
Date submitted
3/04/2023
Date registered
3/08/2023
Date last updated
3/08/2023
Date data sharing statement initially provided
3/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Treatment Resistant Depression Intervention with Psilocybin-assisted Psychotherapy
Scientific title
Investigating the safety, feasibility and acceptability of psilocybin-assisted psychotherapy in treatment resistant depression.
Secondary ID [1] 309342 0
CT-2023-CTN-00313-1
Universal Trial Number (UTN)
U1111-1290-4632
Trial acronym
TRIP-D
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Treatment Resistant Depression 329546 0
Condition category
Condition code
Mental Health 326479 326479 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Psilocybin-assisted psychotherapy consisting of pre psilocybin psychotherapy session/s (preparation), a psilocybin dosing day and post dosing psychotherapy sessions/s (integration).

The initial dose of psilocybin to be administered to all participants will be a 15 mg oral capsule. Study clinicians will assess safety and tolerability post each dosing and only eligible participants will receive a subsequent dose/s (ranging from min 15 mg to maximum 45 mg psilocybin). Minimum number of dosing sessions during the study participation is 1 and maximum 5. Time between all dosing sessions will be at least one week. All dosing sessions will be supervised by a dyad of trained therapists for approximately 7-8 hours.

The psychotherapy sessions prior to dosing (preparation) and post dosing (integration) will occur face to face. The first dosing session is preceded by three preparation sessions and proceeded by two therapy sessions, each of 1 hour duration.

Preparation session/s will involve: building therapeutic alliance, psychological and practical preparation for dosing sessions, non-avoidance training, nature of and relationship to distress and anxiety management strategies, intention setting and planning for continuity of care.

Dosing session/s will involve: Delivery of psilocybin dose in the presence of a therapy dyad and non-directive supervision for 8 hours in the context of a safe and comfortable environment and a curated music playlist.

Integration session/s will involve: Assisting the participant in the formation of a narrative of the psychedelic experience, promoting meaning-centred integration of this narrative into the participants experience, encouraging and motivating behaviour change as a result of the above, encouraging ongoing engagement with emotional and somatic experiences and planning for ongoing support and return to usual care.


Intervention code [1] 325780 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 334319 0
Safety of psilocybin-assisted psychotherapy in treatment resistant depression patients assessed by changes in heart rate, blood pressure, temperature, and monitoring of adverse events. Blood pressure and heart rate will be measured using an automatic blood pressure monitor, and temperature will be assessed using an aural thermometer.

Vital signs (i.e., blood pressure, heart rate and temperature) are measured at baseline, immediately prior to dosing then every 30min for the first two hours following dosing then hourly for 6 hours. Vital signs are measured at all dosing visits. Adverse events are assessed at every study visit according to clinical interview and examination.
Timepoint [1] 334319 0
3 months post psilocybin dosing.
Primary outcome [2] 334546 0
Feasibility of psilocybin-assisted psychotherapy in treatment resistant depression patients by auditing study enrolment/withdrawal logs.
Timepoint [2] 334546 0
3 months post psilocybin dosing.
Secondary outcome [1] 420241 0
Examine the effect of psilocybin-assisted psychotherapy on mood by Montgomery-Asberg Depression Rating Scale (MADRS); response defined as greater or equal to 50% decrease in MADRS score and remission defined as a MADRS score of less or equal to 10.
Timepoint [1] 420241 0
6 months post psilocybin dosing.
Secondary outcome [2] 420242 0
The impact of psilocybin-assisted psychotherapy on quality of life as assessed by the Recovering Quality of Life (REQOL) scale.
Timepoint [2] 420242 0
6 months post psilocybin dosing.
Secondary outcome [3] 421058 0
The impact of psilocybin-assisted psychotherapy on function will be assessed by WHO Disability Assessment Schedule (WHODAS).
Timepoint [3] 421058 0
6 months post psilocybin dosing.
Secondary outcome [4] 424964 0
The impact of psilocybin-assisted psychotherapy on well-being as assessed using the Warwick Edinburgh Mental Well Being Scale (WEMWBS).
Timepoint [4] 424964 0
6 months post-psilocybin dosing

Eligibility
Key inclusion criteria
· Male and female participants 18 - 75 years of age.
· Have given written informed consent.
· Currently under the care of a psychiatrist who is able to provide a referral and willing to maintain ongoing oversight of their patient’s clinical care and treatment management throughout the duration of the study.
· Have a DSM-5 diagnosis of Major Depressive Disorder and currently experiencing a major depressive episode, as confirmed by the study psychiatrist.
· Failed to clinically respond to two different classes of antidepressant medication treatment (despite adequate dose compliance and minimum treatment duration of 6 weeks) during the current major depressive episode.
· Have baseline MADRS score greater than or equal to 20.
· On psychotropic medications at a stable dose for at least 4 weeks and not exceeding recommended upper dose limit according to Australian Medicines Handbook.
· Concurrent psychotherapy is allowed if the type and frequency of the therapy has been stable for at least 4 weeks prior to screening and is expected to remain stable during study participation.
· Will have accompanied transport home after treatment sessions and availability of a friend or family member and home-like environment for the 24 hours following psilocybin dosing.
· Able to engage with psychotherapy.
· Able to be followed up for entire duration of the study (i.e., planning to remain in Sydney for the duration of the study).
· In good general medical health as confirmed by study doctor assessment supported with information from GP/referring psychiatrist.
· Agree to refrain from using any alcoholic beverages or nicotine, within 24 hours of each drug administration. The exception is caffeine.
· Agree to only take medications on the mornings of drug sessions that have been approved by the study psychiatrist.
· Agree to refrain from taking any non-prescription drugs, nutritional supplements, or herbal supplements for one week before each psilocybin administration unless approved by the study psychiatrist.
· Have none or limited lifetime use of hallucinogens (none in last 12 months).
· Worked or studied in a context requiring some proficiency in spoken English (to ensure validity of neuropsychological testing).
· Adequate clinical, ongoing support from own treating psychiatrist and other mental health clinicians, including safety plan in the event of becoming acutely suicidal, as determined by the study psychiatrist.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
· Women who are pregnant, intend to become pregnant during the study or who are currently nursing.
· Have any significant cardiovascular conditions including uncontrolled hypertension.
· Have epilepsy or a history of seizures.
· Have history of any substance use disorder (except nicotine or caffeine) within the past 12 months.
· Currently taking MAOIs, lithium or any other medication that may interfere with the study drug as determined by the study psychiatrist.
· Current or lifetime history of meeting DSM-5 criteria for any psychotic disorders (including mood disorders with psychotic features), or bipolar I or II disorder.
· Have a known first or second-degree relative with any psychotic disorder, or bipolar I or II disorder.
· Significant suicide risk within the past year, as judged by study psychiatrist and informed by C-SSRS.
· Have any condition preventing establishment of rapport and safe psilocybin treatment, as determined by the study psychiatrist.

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
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2023
Actual
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/10/2025
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 25268 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 40017 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 313543 0
Charities/Societies/Foundations
Name [1] 313543 0
Black Dog Institute
Country [1] 313543 0
Australia
Primary sponsor type
Hospital
Name
St. Vincent's Hospital, Sydney
Address
390 Victoria Street,
Darlinghurst,
Sydney, NSW, Australia, 2010
Country
Australia
Secondary sponsor category [1] 315351 0
None
Name [1] 315351 0
Address [1] 315351 0
Country [1] 315351 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312725 0
St. Vincent's Hospital, Sydney Human Research Ethics Committee
Ethics committee address [1] 312725 0
St. Vincent's Hospital
390 Victoria Street,
Darlinghurst, Sydney, NSW, 2010
Ethics committee country [1] 312725 0
Australia
Date submitted for ethics approval [1] 312725 0
28/03/2022
Approval date [1] 312725 0
18/05/2022
Ethics approval number [1] 312725 0
2022/ETH00546

Summary
Brief summary
This is a single centre, single arm study primarily examining the the safety, feasibility and acceptability of psilocybin-assisted psychotherapy in treatment resistant depression patients who are on concurrent psychotropic medication.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125682 0
A/Prof Jonathan Brett
Address 125682 0
Clinical Therapeutics
Level 2 Xavier Building
St. Vincent's Hospital
390 Victoria Street, Darlinghurst
Sydney, NSW
2010
Country 125682 0
Australia
Phone 125682 0
+61 2 8382 1111
Fax 125682 0
Email 125682 0
jonathan.brett@svha.org.au
Contact person for public queries
Name 125683 0
A/Prof Jonathan Brett
Address 125683 0
Clinical Therapeutics
Level 2 Xavier Building
St. Vincent's Hospital
390 Victoria Street, Darlinghurst
Sydney, NSW
2010
Country 125683 0
Australia
Phone 125683 0
+61 2 8382 1111
Fax 125683 0
Email 125683 0
jonathan.brett@svha.org.au
Contact person for scientific queries
Name 125684 0
A/Prof Jonathan Brett
Address 125684 0
Clinical Therapeutics
Level 2 Xavier Building
St. Vincent's Hospital
390 Victoria Street, Darlinghurst
Sydney, NSW
2010
Country 125684 0
Australia
Phone 125684 0
+61 2 8382 1111
Fax 125684 0
Email 125684 0
jonathan.brett@svha.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


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.