Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000827639
Ethics application status
Approved
Date submitted
28/04/2023
Date registered
1/08/2023
Date last updated
16/10/2023
Date data sharing statement initially provided
1/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
PARTING: Psilocybin-Assisted suppoRtive psychoTherapy IN the treatment of prolonged Grief; a phase II feasibility safety trial
Scientific title
PARTING: Assessing the feasibility, acceptability and safety of Psilocybin-Assisted suppoRtive psychoTherapy IN the treatment of prolonged Grief in bereaved cancer carers.
Secondary ID [1] 309530 0
Nil known.
Universal Trial Number (UTN)
U1111-1291-8864
Trial acronym
PARTING
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prolonged grief disorder 329816 0
Condition category
Condition code
Mental Health 326713 326713 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This psilocybin-assisted psychotherapy intervention involves a combination of pharmacological and psychological treatment.
All participants will receive three psychotherapy sessions anticipated to take 1.5 hours each, 1, 2 and 3 days before the 8-hour psilocybin dosing session, then four psychotherapy sessions anticipated to take 1.5 hours, 1 day, then 1, 2 and 4 weeks after the dosing session.
The psychotherapy focuses on three distinct phases: (1) Preparation: emphasizing therapeutic alliance, non-avoidance training, psychological and practical preparation for dosing sessions, nature of and relationship to distress, anxiety management strategies, the importance of set and setting, and intention formation; (2) Dosing session: establishing suitable set and setting, non-directive support; (3) Integration: processing what came up in the psilocybin session including any memories of the death and loss (i.e. blocks) and rebuilding by teaching specific strategies in cognitive restructuring to reframe common maladaptive grief-related appraisals (e.g. hopelessness and guilt), communication with the deceased to manage unfinished business and goal setting and/or reintegration into a life that they actually want to live (i.e. beginning the process of making changes to their life following the experience and consider how these may be continued and expanded. The final session will include referral pathways for post-care).
The investigational product (WP002 psilocybin Trihydrate [3-[2-(dimethylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate) will be provided by Woke pharmaceuticals and the dose of the psilocybin tablet used in the study is 25 mg administered orally with water.
All participants will be seen by the same two therapists (a clinical psychologist and a nurse) in all the psychotherapy sessions and during the psilocybin session. A trial psychiatrist will oversee baseline medical assessments on dose day and be present in the building during the duration of the psilocybin dosing session in case medication and management of any severe adverse events is required.
The trial psychologists and trial nurses are qualified and experienced mental health professionals (including two clinical psychologists and two nurses with specialty training in bereavement counselling). The trial psychologists, nurses, psychiatrist and the lead investigator have undergone professional development training in psilocybin-assisted therapy and prolonged grief therapy order to facilitate this treatment approach safely and successfully. The intervention is supported by a therapy manual developed by the investigator team who are leading experts in psilocybin-assisted psychotherapy and prolonged grief therapy. Moreover, all clinicians on the trial will meet with CI Renee Harvey for ongoing clinical supervision.

Descriptive statistics assessing feasibility will include: (i) recruitment rate (enrolled/invited participants); (ii) retention rate (completed seven sessions/enrolled participants); (ii) fidelity to three follow-up questionnaires at 1 day and 6 and 12 weeks post dosing day (questionnaires completed/active participants). Should participants consent, treatment fidelity will also be monitored via video recordings of all intervention phases. Finally, REDCap session logs will also monitor fidelity to the manualized intervention.
Intervention code [1] 325958 0
Treatment: Drugs
Intervention code [2] 325959 0
Behaviour
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 334577 0
Feasibility as measured by: (i) recruitment rate (enrolled/invited participants), (ii) retention rate (completed seven sessions/enrolled participants), (ii) fidelity to follow-up assessments (surveys and clinical interviews completed/active participants).
All Measures will be assessed as a composite primary outcome. The source for feasibility data is an audit of study enrolment/withdrawal REDCap logs.
Timepoint [1] 334577 0
Cumulative data will be assessed at the conclusion of the study.
Primary outcome [2] 334578 0
Intervention acceptability: Following participants’ final intervention session (5 weeks after dose day), participants will be asked to take part in a semi-structured evaluation interview about their experience of the intervention acceptability. We will also ask the nurses and psychologists to complete an evaluation interview at the end of the trial.
All measures will be assessed as a composite primary outcome.
Timepoint [2] 334578 0
5 weeks after dose day
Primary outcome [3] 334579 0
Psilocybin safety as measured by: (i) adverse events and, a pre-post psilocybin comparison of: (ii) vital signs; (iii) biochemistry and haematology profile and; (iv) ECG findings.
All measures will be assessed as a composite primary outcome.

Psilocybin may cause small increases in blood pressure and heart rate or headaches. Both blood pressure and heart rate will be monitored and recorded throughout the session by the trial nurse.

Psilocybin can also cause temporary anxiety, nausea, impaired concentration, altered perception of time, altered visual perception, mild paranoia and a range of emotions. Anxiety sometimes occurs for people while the psilocybin is first taking effect. Very rarely people may experience agitation or severe anxiety that does not respond to supportive therapy. Observations about movements, expressions, vocalisations, requests, medications given or actions taken will be monitored and recorded throughout the session by the trial clinicians.

The rates of any lasting psychological symptoms are extremely rare (8 in 10,000 people or 0.08%). If any psychological effects persist after the psilocybin session, these will be managed in the following psychotherapy session(s).

Participants are provided with a self-reported events diary at the start of the intervention to record the dates and description of complications or difficult experiences at any time during the study follow-up. Our trial staff will ask about these events every time they are in contact with them.

Heart Rate is assessed using pulse oximeter and blood pressure is assessed automatic blood pressure monitor.

Full Blood count testing:
Haemoglobin Adult Male 130-180 g/l
Haemoglobin Adult female 115-165 g/l
White Cell Count Adult 3.6-11.0 x109/l
Platelet count Adult 140-400 x109/l
Timepoint [3] 334579 0
(i)From enrollment/baseline to end of follow-up (i.e. 12 weeks after psilocybin dosing day)
(ii)Enrolment/baseline and 1 days post-psilocybin dosing
(iii)Enrolment/baseline and 1 days post-psilocybin dosing
(iv)Enrolment/baseline and 1 days post-psilocybin dosing
Secondary outcome [1] 421271 0
Changes in the outcome measures of grief symptoms on the Prolonged Grief Disorder Scale (PG-13-Revised)
Timepoint [1] 421271 0
Enrolment/baseline, then 1 day, 6 weeks and 12 weeks after psilocybin dosing day.
Secondary outcome [2] 421720 0
Changes in the outcome measures of grief symptoms with the Clinical Interview developed by the Chief Investigator and mapped to diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders version 5.
Timepoint [2] 421720 0
Enrolment/baseline, then 1 day, 6 weeks and 12 weeks after Psilocybin dosing day
Secondary outcome [3] 421721 0
Changes in the outcome measures of grief symptoms of the Depression, Anxiety, Stress Scale (DASS 21).
Timepoint [3] 421721 0
Enrolment/baseline, then 1 day, 6 weeks and 12 weeks after Psilocybin dosing day
Secondary outcome [4] 421723 0
Changes in the outcome measures of grief symptoms of the Watts Connectedness Scale (WCS)
Timepoint [4] 421723 0
Enrolment/baseline, then 1 day, 6 weeks and 12 weeks after Psilocybin dosing day.
Secondary outcome [5] 421725 0
Changes in the outcome measures of grief symptoms of the SF-6D Quality Adjusted Life Year Measure
Timepoint [5] 421725 0
Enrolment/baseline, then 1 day, 6 weeks and 12 weeks after Psilocybin dosing day.

Eligibility
Key inclusion criteria
• Adult bereaved carer of a patient who died from cancer more than 12 months ago
• Meets the threshold for prolonged grief disorder as measured on the validated Prolonged Grief Disorder Scale (PG-13-Revised) and in a clinical interview.
• Under the care of a psychiatrist, psychologist, physician, or general practitioner
• Proficient in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires
• Living in Brisbane QLD or able to travel to Brisbane for the in-person intervention sessions
• Intention to complete all 8 intervention sessions
• Agree to have their drug dosing sessions recorded to video for treatment fidelity and clinical supervision.
• Able to swallow pills.
• Treating medical doctor can confirm patient has safely tapered and washed-out current antidepressant pharmacotherapy prior to baseline assessment.
• Agree to be abstinent from illicit drugs or medications outside of your usual and allowed prescribed medications and alcohol use for at least 2 days prior to psilocybin dosing.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Disorder with known central nervous system involvement
• In treatment in another clinical trial involving an investigational product
• Hepatic dysfunction
• Hypercalcaemia, Cushing's syndrome, hypoglycaemia, syndrome of inappropriate antidiuretic hormone secretion, or carcinoid syndrome.
• Cardiovascular conditions
• Currently on preventative medication for migraines
• Epilepsy
• Positive pregnancy test or trying to get pregnant
• Current hypothyroidism or hyperthyroidism as identified by blood test
• Weight less than 40 kg or has a body mass index <15.
• Use of any hallucinogen or psychedelic drug within the past 12 months
• Any significant adverse events after prior use of any hallucinogen or psychedelic
• Medications that may have interactions with psilocybin
• Diagnosed psychotic disorder or severe post-traumatic stress disorder
• First-degree family member with a diagnosed psychotic disorder
• History of suicide attempts or mania
• Moderate-severe drug or alcohol dependence
• Are unable to give adequate informed consent

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 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Based on sample size recommendations for pilot studies assessing feasibility and acceptability and our experience we plan to enroll 15 participants in the intervention to provide the sufficient range of experience for qualitative data saturation (i.e. the point where no new information is obtained in our qualitative evaluation interviews) and provide reliable information about the acceptability of the intervention.
Qualitative Analysis of Participants Experience (acceptability/potential efficacy)
The inductive, comparative, and cyclic analytic procedure will include initial coding of text into researcher-created codes (labels); comparable codes and their text grouped into research-created categories (potential themes); reviewing themes in relation to the coded extracts and the entire data set and generating a thematic ‘map’ of the analysis; defining and naming themes in relation to the overall story the analysis tells.
Quantitative Analysis of Psilocybin Experience Questions
Descriptive statistics (n,%; mean, SD) will be used to summarize questionnaire item results about mystical experience, meaning and challenge experienced in relation to taking psilocybin.



Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
13/11/2023
Actual
Date of last participant enrolment
Anticipated
29/01/2024
Actual
Date of last data collection
Anticipated
22/04/2024
Actual
Sample size
Target
15
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 313721 0
Other
Name [1] 313721 0
QIMR Berghofer Medical Research Institute
Country [1] 313721 0
Australia
Funding source category [2] 313722 0
Commercial sector/Industry
Name [2] 313722 0
Woke Pharmaceuticals
Country [2] 313722 0
Australia
Primary sponsor type
Other
Name
QIMR Berghofer Medical Research Institute
Address
300 Herston Rd, Herston QLD 4006
Country
Australia
Secondary sponsor category [1] 315536 0
None
Name [1] 315536 0
Address [1] 315536 0
Country [1] 315536 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312893 0
QIMR Berghofer Medical Research Institute Human Research Ethics
Ethics committee address [1] 312893 0
300 Herston Road, Herston QLD 4006
Ethics committee country [1] 312893 0
Australia
Date submitted for ethics approval [1] 312893 0
23/08/2021
Approval date [1] 312893 0
06/06/2023
Ethics approval number [1] 312893 0
P3801

Summary
Brief summary
While grief is a normal reaction to loss, 30% of cancer carers are reported to experience prolonged grief disorder. Patients with prolonged grief require grief-focused intervention in addition to the depression-focused treatment. Psilocybin-assisted psychotherapy is an experimental intervention that could reduce grief-related distress and suffering.

PARTING is a single-arm (open-label) study of a psilocybin-assisted psychotherapy trial. This study aims to determine whether this new treatment is acceptable to and safe for participants and to establish an initial impression of its effectiveness in treating people with prolonged grief. It will include approximately 15 participants.

Bereaved carers of people with cancer who meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) criteria for prolonged grief disorder will be invited to take part in PARTING. Potential participants will undergo rigorous screening before enrolment to meet general medicine and psychiatric eligibility criteria. The intervention will include three psychotherapy sessions in preparation for one psilocybin dosing session and then four post-experience psychotherapy integration sessions. All participants’ sessions will involve a trial psychologist and a trial nurse being present.

Baseline and follow-up survey and clinical assessments will measure prolonged grief symptoms i.e. the outcome for the future full-scale trial. Following participants’ final intervention session, participants will complete a semi-structured evaluation interview about their experience. Responses will be transcribed and qualitatively analysed using thematic analysis.

The 15 evaluation interviews with participants will provide information about intervention acceptability and a qualitative initial impression of efficacy and will be used to refine the intervention. As a secondary analysis of potential efficacy we will also explore changes in grief scores. We postulate that the treatment will be well tolerated and accepted and grief symptoms will be substantially reduced.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126246 0
A/Prof Vanessa Beesley
Address 126246 0
QIMR Berghofer
300 Herston Road, Herston QLD 4006
Country 126246 0
Australia
Phone 126246 0
+61 7 3362 0270
Fax 126246 0
Email 126246 0
Vanessa.Beesley@qimrberghofer.edu.au
Contact person for public queries
Name 126247 0
Ms Hanna Beebe
Address 126247 0
QIMR Berghofer
300 Herston Road, Herston QLD 4006
Country 126247 0
Australia
Phone 126247 0
+61 7 3362 0286
Fax 126247 0
Email 126247 0
PartingTrial@qimrberghofer.edu.au
Contact person for scientific queries
Name 126248 0
A/Prof Vanessa Beesley
Address 126248 0
QIMR Berghofer
300 Herston Road, Herston QLD 4006
Country 126248 0
Australia
Phone 126248 0
+61 7 3362 0270
Fax 126248 0
Email 126248 0
Vanessa.Beesley@qimrberghofer.edu.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.