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Trial registered on ANZCTR


Registration number
ACTRN12621000560897
Ethics application status
Approved
Date submitted
3/03/2021
Date registered
12/05/2021
Date last updated
15/04/2024
Date data sharing statement initially provided
12/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and tolerability of psilocybin-assisted physiotherapy in healthy volunteers
Scientific title
Safety and tolerability of psilocybin-assisted physiotherapy in healthy volunteers
Secondary ID [1] 303578 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Functional neurological disorder 320948 0
Condition category
Condition code
Mental Health 318755 318755 0 0
Other mental health disorders
Neurological 318756 318756 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This feasibility and pilot study will assess the safety and tolerability of performing basic movement tasks (prescribed by a physiotherapist) following administration of psilocybin in healthy volunteers. The findings from this study will be used to guide the dosage of psilocybin in the companion study (‘Psilocybin-assisted therapy for refractory Functional Neurological Disorder’).

12 healthy participants will be recruited on a volunteer basis for this study. Each participant will receive three separate doses of psilocybin (5mg, 10mg, 15mg or 20mg) according to a Williams study design. Six participants will receive 5, 10 & 15mg and six will receive 10, 15 & 20mg. Each dose will be randomly assigned and taken at least 1 week apart.

After providing written consent to participate in the study, participants will be assessed by a physician and psychiatrist to ensure study eligibility criteria is satisfied. If eligible, a preparation session facilitated by a mental health professional (for example, a psychiatrist or psychologist) will occur approximately one week before the participant’s first psilocybin dosing session. This will take place in dedicated room at the Austin Hospital where the dosing sessions will occur. The preparation session will consist of a discussion about drug administration, the psychoactive effects of psilocybin, and a trial of the movement tasks that will be performed during each dosing session (see below). Participants will be encouraged to raise any queries or concerns they have about the study which will be addressed by the mental health professional.

On the day of psilocybin administration, the participant will arrive approximately 1 hour before dosing so trial staff can re-confirm their eligibility (including review of medication status), and record baseline vital sign measurements (heart rate, blood pressure, pulse oximetry). Psilocybin will be administered orally (capsule form) with a glass of water under the supervision of trial staff. Vital signs will be checked at hourly intervals up to 5 hours after dosing. Throughout each dosing session, participants will be asked to complete a series of movement tasks adapted from the De Morton Mobility Index and the Physio4FMD randomised controlled trial (de Morton NA, Davidson M, Keating JL, 2008; Nielsen G, et al., 2019). The trial physiotherapist will assess the participant’s ability to complete each task following an assessment form created by the researchers for the purposes of this study.

At the end of each dosing session, the participant will be provided an opportunity to debrief with trial staff about their experiences, including adverse events. They will also be contacted by trial staff the following morning to assess for delayed side effects/adverse events since leaving the hospital.

In addition, participants will be asked to complete a resting state fMRI brain scan prior to their first and second dose of psilocybin (baseline and follow-up scans respectively).
Intervention code [1] 319869 0
Treatment: Drugs
Intervention code [2] 320173 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326705 0
Ability of participants to complete a series of physiotherapist-prescribed movement tasks (adapted from the de Morton Mobility Index (DEMMI) and the Physio4FMD trial) after receiving 3 separate doses of psilocybin (5mg, 10mg, 15mg and/or 20mg). Participants' ability to complete these tasks will be assessed by the trial physiotherapist during each dosing session, as well as rated by an independent physiotherapist (blinded to the participant's psilocybin dose) via review of de-identified video recordings.
Timepoint [1] 326705 0
During preparation session (1 week prior to receiving first dose of psilocybin), and 1, 2 and 4 hours following each administration of psilocybin.
Primary outcome [2] 326706 0
Participant reported and/or clinician observed adverse events following administration of each psilocybin dose (5mg, 10mg, 15mg and/or 20mg). Adverse events may include, but are not limited to, nausea, paraesthesia, dizziness, elevated blood pressure, fatigue, headache, and/or anxiety. Study staff will document all adverse events in a study specific adverse event form (which includes fields to capture AE severity, expectedness and outcome). All AEs will be reviewed by the medical investigators to determine causality to the investigational medicinal product and any required course of action.
Timepoint [2] 326706 0
i) during the psilocybin dosing session (during the acute effects of the drug)
ii) after the effects of the drug have subsided (before participant leaves the hospital)
iii) 24 hours after psilocybin was taken by the participant (trial staff will telephone participants the morning after psilocybin administration)
Secondary outcome [1] 392413 0
Participants' experiences of the intervention as outlined in a one-on-one in-depth interview with trial staff (qualitative data collection).
Timepoint [1] 392413 0
The feedback interview will be conducted within 1-week of the participant's final dose of psilocybin
Secondary outcome [2] 392414 0
Performance of healthy participants on a computer task to assess sense of motor agency.

The computer task has been used to assess sense of agency in mental health conditions such as schizophrenia and autism (see Zalla et al, Metacognition of agency and theory of mind in adults with high functioning autism, Conscious Cognit 2015). The code for this task has been provided free of charge by the authors.
Timepoint [2] 392414 0
Prior to each psilocybin dose (baseline), and after participants complete their first series of movement tasks (approx. 1 hour after drug administration)
Secondary outcome [3] 421515 0
Within-subject changes of resting state fMRI-derived measures of brain functional connectivity after 1st dose of psilocybin compared to baseline
Timepoint [3] 421515 0
Prior to the participant's first dose (baseline scan) and 2nd dose (follow-up scan) of psilocybin.

Eligibility
Key inclusion criteria
Adults aged 18 to 65 years, without a history of Functional Neurological Disorder (FND), who have volunteered for the study.

Capacity to provide informed consent
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
--- Medical exclusion criteria ---

Cardiovascular conditions: poorly-controlled hypertension, angina, ischemic heart disease, a clinically significant ECG abnormality (e.g. atrial fibrillation), transient ischemic attack (TIA), stroke, peripheral or pulmonary vascular disease (no active claudication).

A diagnosis of epilepsy or previous epileptic seizures.

Diagnosis of dementia

A history of Chronic Kidney Disease or Chronic Liver Disease

Known conditions putting the participant at risk for hypercalcaemia, Cushing's syndrome, hypoglycaemia, syndrome of inappropriate antidiuretic hormone secretion, or carcinoid syndrome.

Insulin-dependent diabetes; if taking oral hypoglycaemic agents, the participant is only excluded if they also have a history of hypoglycaemia.

Females who are pregnant, nursing or trying to conceive.

Use of medications contraindicated with psilocybin, that are inappropriate to cease for the necessary time period before/after the dosing session.

Patients enrolled in another clinical trial involving an investigational product.


--- Psychological exclusion criteria ---

Current or previous diagnosis of any psychotic disorder, including Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder, Brief Psychotic Disorder, Delusional Disorder, Schizotypal Personality Disorder, Substance/Medication-Induced Psychotic Disorder or Psychotic Disorder due to another medical condition.

Current or previous diagnosis of Bipolar disorder.

First degree relative with diagnosed Schizophrenia, Psychotic Disorder, or Bipolar Disorder.

A history of attempted suicide or mania.

Current or previous diagnosis of substance use disorder (excluding caffeine and nicotine).

Previous regular use, or current use of psychedelic agents.

Current diagnosis of other psychiatric conditions judged to be incompatible with safe exposure to psilocybin

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)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
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/efficacy
Statistical methods / analysis
A detailed statistical analysis plan describing all analyses to be performed will be finalised before the final analysis. The statistical analysis will be descriptive, no hypothesis will be tested. Any inferential testing or models will be considered exploratory in nature.

Data will be summarised. Summaries will consist of descriptive statistics whereby continuous variables will be summarized using n (non-missing sample size), mean, standard deviation, median, minimum, and maximum and categorical variables using counts and percentages (based on the non-missing sample size) of observed category levels. For the healthy participants, summaries will be presented by dose-level.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
9/06/2023
Actual
9/07/2023
Date of last participant enrolment
Anticipated
9/01/2024
Actual
17/01/2024
Date of last data collection
Anticipated
9/02/2024
Actual
28/02/2024
Sample size
Target
12
Accrual to date
Final
13
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 24667 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 24668 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment postcode(s) [1] 40287 0
3084 - Heidelberg
Recruitment postcode(s) [2] 40288 0
3081 - Heidelberg West

Funding & Sponsors
Funding source category [1] 307999 0
Hospital
Name [1] 307999 0
Austin Health
Country [1] 307999 0
Australia
Funding source category [2] 308005 0
University
Name [2] 308005 0
Melbourne School of Psychological Sciences, University of Melbourne
Country [2] 308005 0
Australia
Funding source category [3] 308006 0
Other Collaborative groups
Name [3] 308006 0
Usona Institute
Country [3] 308006 0
United States of America
Primary sponsor type
Hospital
Name
Austin Health
Address
145 Studley Road
PO Box 5555
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 308728 0
None
Name [1] 308728 0
None
Address [1] 308728 0
None
Country [1] 308728 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307993 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 307993 0
Ethics committee country [1] 307993 0
Australia
Date submitted for ethics approval [1] 307993 0
Approval date [1] 307993 0
22/02/2021
Ethics approval number [1] 307993 0

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

Contacts
Principal investigator
Name 109162 0
Prof Richard Kanaan
Address 109162 0
Department of Psychiatry, University of Melbourne
Level 10, Lance Townsend Building
Austin Hospital
PO Box 5555
Heidelberg VIC 3084
Country 109162 0
Australia
Phone 109162 0
+61 3 9496 3351
Fax 109162 0
Email 109162 0
[email protected]
Contact person for public queries
Name 109163 0
Alexander Bryson
Address 109163 0
Department of Neurology
PO Box 5555
145 Studley Road
Heidelberg VIC 3084
Country 109163 0
Australia
Phone 109163 0
+61 3 94965000
Fax 109163 0
Email 109163 0
[email protected]
Contact person for scientific queries
Name 109164 0
Alexander Bryson
Address 109164 0
Department of Neurology
PO Box 5555
145 Studley Road
Heidelberg VIC 3084
Country 109164 0
Australia
Phone 109164 0
+61 3 94965000
Fax 109164 0
Email 109164 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Our participant information and consent form does not ask for consent for IPD to be made publicly available. Data obtained in this pilot and feasibility study will be used to inform the development of a future project conducted by the researchers (Psilocybin assisted physiotherapy for refractory motor FND).


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.