Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000578808
Ethics application status
Approved
Date submitted
13/04/2021
Date registered
17/05/2021
Date last updated
29/07/2024
Date data sharing statement initially provided
17/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Psilocybin-assisted physiotherapy for refractory Functional Neurological Disorder
Scientific title
Efficacy and tolerability of psilocybin-assisted physiotherapy on motor symptoms in refractory Functional Neurological Disorder
Secondary ID [1] 303868 0
None
Universal Trial Number (UTN)
Trial acronym
PsyFND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Functional neurological disorder 321441 0
Condition category
Condition code
Mental Health 319201 319201 0 0
Other mental health disorders
Neurological 319202 319202 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This pilot and feasibility study will assess the safety and obtain preliminary evidence for the efficacy of psilocybin-assisted physiotherapy for refractory motor Functional Neurological Disorder. This is a single-centre trial and all intervention and assessments will be completed at either the Austin Hospital or Heidelberg Repatriation Hospital (Melbourne, Australia).

Twenty-four patients with refractory motor FND will be recruited for this trial. Twelve participants will be randomised to receive a single dose of oral Psilocybin (15mg). This comprises the “low dose” arm of the study. Twelve additional participants will be randomised to receive a single 25mg dose of oral psilocybin. This comprises the “standard dose” arm.

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 psilocybin dosing session. This will take place in a dedicated room at the Austin Hospital where Psilocybin administration will occur. The preparation session will consist of a discussion about drug administration, the psychoactive effects of psilocybin, and the rationale for combining Psilocybin with physiotherapy treatments. Participants will be encouraged to raise any queries or concerns they have about the study which will be addressed by the mental health professional.

Participants will complete 2 physiotherapy sessions with the trial physiotherapist in the days prior to receiving Psilocybin. These sessions will include an initial assessment to obtain an in-depth understanding of the participants movement problems; development of a treatment plan; and explaining the diagnosis of FND following a standardised explanatory model. Participants will complete (baseline) self-report questionnaires prior to their first session with the physiotherapist (see ‘Outcomes’).

On the day of drug administration, participants will arrive approximately 1½ hours before dosing. Trial staff will review the participant’s details and eligibility, and record baseline vital signs measurements. Psilocybin will be provided in capsule form (5mg per capsule) with a glass of water and taken orally under the supervision of trial staff in a room equipped with monitoring equipment (blood pressure, heart rate, pulse oximetry) and an emergency alarm. Vital signs will be checked at hourly intervals up to 5 hours after dosing. Any adverse events – as reported by the participant and/or observed by study staff – will be recorded. During the dosing session, participants in the “low dose” arm 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. Participants randomised to the “standard dose” arm will not be asked to complete these movement tasks.

At the end of the 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 day to assess for delayed side effects/adverse events since leaving the hospital.

All participants will be encouraged to resume their physiotherapy treatment within 24-48 hours after psilocybin administration. A further 3 to 6 sessions will be completed designed to relieve patients’ predominant functional motor complaints. The number of sessions will be determined collaboratively between the participant and trial physiotherapist, for example, informed by symptom improvement, and participants’ tolerance of the therapy. A physiotherapist experienced in treating patients with neurological conditions will provide the treatment face-to-face and one-to-one at the Austin Hospital. Each session will last approximately 60 minutes. During the course of the physiotherapy regime, a study-specific workbook will be completed by both the participant and trial physiotherapist to help guide the intervention, and to provide a record of the content of the sessions. Participants will be encouraged to complete all physiotherapy treatment sessions (i.e., 2 prior to psilocybin dosing, and 3-6 sessions thereafter) within a 3-week period.

Treatment fidelity to the physiotherapy regime will be measured by the following:
1. Fidelity at the level of the physiotherapist. The physiotherapist providing the treatment will complete a checklist for each participant. This checklist will be based on the TIDIER checklist description.
2. Fidelity at the level of the participant. The content, length and number of physiotherapy sessions by participant report will be monitored with a structured telephone survey. The survey will be conducted by study staff as soon as possible after completion of the physiotherapy treatment regime.
3. Independent assessment of fidelity. A random sample of completed physiotherapy workbooks will be assessed. The workbook guides the intervention and is completed during the treatment session by both the participant and physiotherapist. It therefore provides a record of the content of sessions. The workbooks will be assessed against a predetermined set of criteria to determine the extent to which treatment followed the intervention protocol.

Participants will be assessed immediately after; 1-week; and 1-month after their final physiotherapy session. The trial physiotherapist will reassess their motor symptoms, and participant self-report questionnaires will be provided. At 1-week follow-up, participants will be invited to attend a one-to-one, semi-structured interview with study staff so they can provide feedback about their experiences of the intervention.

In addition, participants will be asked to complete a resting state and task-based fMRI brain scan in the days prior their first physiotherapy session (baseline scan), and after they complete their final session (follow-up scan).
Intervention code [1] 320174 0
Treatment: Drugs
Intervention code [2] 326077 0
Rehabilitation
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327074 0
Participant-reported Clinical Global Impression of Severity of FND symptoms.

Clinical Global Impression is a 7 point scale denoting symptom severity (1 = normal; 7 = extremely ill) or symptom improvement (1 = very much improved; 7 = very much worse).
Timepoint [1] 327074 0
At baseline (prior to commencing physiotherapy treatment); after completion of participants' final physiotherapy treatment session; 1 week after intervention with psilocybin-assisted physiotherapy; 1 month after intervention with psilocybin-assisted physiotherapy
Primary outcome [2] 327075 0
Individualised scale of Functional Motor Disability according to motor symptoms:

Lower limb weakness & gait disturbance:
-10-meter walk test
-5 times sit-to-stand test

Upper limb weakness:
-9-hole peg test

Movement disorder:
-Simplified Functional Movement Disorder Rating Scale (Pick et al., Outcome measurement in functional neurological disorder: a systematic review and recommendations, JNNP 2020)
Timepoint [2] 327075 0
At baseline (prior to commencing physiotherapy treatment); after completion of participants' final physiotherapy treatment session; 1 week after intervention with psilocybin-assisted physiotherapy; 1 month after intervention with psilocybin-assisted physiotherapy
Primary outcome [3] 327480 0
Participant-reported Clinical Global Impression of Improvement of FND symptoms.

Clinical Global Impression is a 7 point scale denoting symptom severity (1 = normal; 7 = extremely ill) or symptom improvement (1 = very much improved; 7 = very much worse).
Timepoint [3] 327480 0
After completion of their final physiotherapy treatment session; 1 week after intervention with psilocybin-assisted physiotherapy; 1 month after intervention with psilocybin-assisted physiotherapy
Secondary outcome [1] 393687 0
Clinician-rated severity of functional motor symptoms graded through video assessment.

A clinical video based on a standardised protocol to assess functional motor symptoms will be used (Hinson et al, Rating scale for psychogenic movement disorders: Scale development and clinimetric testing, Movement Disorders 2005). The video will contain a full-body view, close-up to the head, hands and legs, and a functional assessment of speech, finger-nose testing, finger taps, repetitive hand movements, heel taps, standing/posture, walking and postural stability. All trial participants will be de-identified on video with facial blurring.
Timepoint [1] 393687 0
At baseline (prior to commencing physiotherapy treatment); after completion of participants' final physiotherapy treatment session; 1 week after intervention with psilocybin-assisted physiotherapy; 1 month after intervention with psilocybin-assisted physiotherapy
Secondary outcome [2] 393688 0
Clinician-reported Clinical Global Impression of Severity of FND Symptoms
Timepoint [2] 393688 0
At baseline (prior to commencing physiotherapy treatment); after completion of participants' final physiotherapy treatment session; 1 week after intervention with psilocybin-assisted physiotherapy; 1 month after intervention with psilocybin-assisted physiotherapy
Secondary outcome [3] 393689 0
Short Form 36 questionnaire to measure life impact of FND symptoms, as rated by the participant (Ware et al, The MOS 36-ltem Short-Form Health Survey (SF-36), Medical Care 1992)
Timepoint [3] 393689 0
At baseline (prior to commencing physiotherapy treatment); after completion of participants' final physiotherapy treatment session; 1 week after intervention with psilocybin-assisted physiotherapy; 1 month after intervention with psilocybin-assisted physiotherapy
Secondary outcome [4] 393690 0
FND-associated somatic symptoms measured through the Patient Health Questionnaire 15 (Carson et al, Somatic symptom count scores do not identify patients with symptoms unexplained by disease: A prospective cohort study of neurology outpatients, JNNP 2015)
Timepoint [4] 393690 0
At baseline (prior to commencing physiotherapy treatment); after completion of participants' final physiotherapy treatment session; 1 week after intervention with psilocybin-assisted physiotherapy; 1 month after intervention with psilocybin-assisted physiotherapy
Secondary outcome [5] 395287 0
Clinician-reported Clinical Global Impression of Improvement of FND Symptoms
Timepoint [5] 395287 0
At baseline (prior to commencing physiotherapy treatment); after completion of participants' final physiotherapy treatment session; 1 week after intervention with psilocybin-assisted physiotherapy; 1 month after intervention with psilocybin-assisted physiotherapy
Secondary outcome [6] 421891 0
Participant reported depression symptoms measured by the Patient Health Questionnaire 9-item
Timepoint [6] 421891 0
At baseline (prior to commencing physiotherapy treatment); after completion of participants' final physiotherapy treatment session; 1 week after intervention with psilocybin-assisted physiotherapy; 1 month after intervention with psilocybin-assisted physiotherapy
Secondary outcome [7] 421892 0
Participant reported anxiety symptoms measured by the GAD-7 Anxiety
Timepoint [7] 421892 0
At baseline (prior to commencing physiotherapy treatment); after completion of participants' final physiotherapy treatment session; 1 week after intervention with psilocybin-assisted physiotherapy; 1 month after intervention with psilocybin-assisted physiotherapy
Secondary outcome [8] 421893 0
Participant reported experiences of altered states of consciousness following Psilocybin administration measured by the 5-dimension altered states of consciousness scale (5D-ASC)
Timepoint [8] 421893 0
Completed by the participant at the end of the Psilocybin dosing session
Secondary outcome [9] 421894 0
Participant reported experience of ego-dissolution following Psilocybin administration measured by the 8-item Ego-dissolution inventory (EDI)
Timepoint [9] 421894 0
Completed by the participant at the end of the Psilocybin dosing session
Secondary outcome [10] 421895 0
Participant reported expectations of treatment assessed using the Stanford Expectations of Treatment Scale (SETS), a six-point scale that measures positive and negative expectancy of treatment .
Timepoint [10] 421895 0
Completed by participants prior to commencing the physiotherapy intervention (baseline)
Secondary outcome [11] 421896 0
**Primary outcome** safety of Psilocybin assisted physiotherapy measured by the presence of adverse events as reported by the participant and/or observed by trial staff.
Adverse effects may include, but are not limited to, the following:
o Worsening of motor FND symptoms
o Anxiety, headache, confusion, paranoia, nausea, or any other symptoms sufficient to cause distress to the participant
o Hypertension, tachycardia, hypoxia
Timepoint [11] 421896 0
During Psilocybin dosing session; the day after dosing (phone call with trial staff); during each physiotherapy treatment session; 1-week and 1-month post final physiotherapy session
Secondary outcome [12] 421897 0
**Primary outcome for low-dose arm participants only** Ability of participants in "low-dose" psilocybin arm to complete a series of physiotherapist-prescribed movement tasks (adapted from the de Morton Mobility Index (DEMMI) and the Physio4FMD trial). Participants' ability to complete these tasks will be assessed by the trial physiotherapist during the dosing session, as well as rated by an independent physiotherapist via review of a de-identified video recording.
Timepoint [12] 421897 0
Approximately 1 hour, 2 hours and 4 hours after receiving low-dose Psilocybin

Eligibility
Key inclusion criteria
Adults aged 18 to 65 years with a diagnosis of refractory motor FND. The diagnosis must be supported by relevant neurological investigations and independent assessment by a psychiatrist and neurologist. Refractory motor FND is defined as upper or lower limb motor weakness, gait disorder or movement disorder (e.g. tremor) of at least 6 months duration.

Participants must have previously received physiotherapy and psychiatry management.

Participants must demonstrate an understanding of their diagnosis of FND and capacity to provide informed consent for the study.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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 seizures.

A 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 I or II disorder.

First degree relative with diagnosed Schizophrenia, Psychotic Disorder, or Bipolar I or II 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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
31/05/2024
Actual
15/05/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/07/2025
Actual
Sample size
Target
24
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 24715 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 24716 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment postcode(s) [1] 40334 0
3084 - Heidelberg
Recruitment postcode(s) [2] 40335 0
3081 - Heidelberg West

Funding & Sponsors
Funding source category [1] 308263 0
Hospital
Name [1] 308263 0
Austin Health
Country [1] 308263 0
Australia
Funding source category [2] 308266 0
University
Name [2] 308266 0
Melbourne School of Psychological Sciences, University of Melbourne
Country [2] 308266 0
Australia
Funding source category [3] 308267 0
Other Collaborative groups
Name [3] 308267 0
Usona Institute
Country [3] 308267 0
United States of America
Primary sponsor type
Hospital
Name
Austin Health
Address
Level 8, Harold Stokes Building
Austin Hospital
145 Studley Rd
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 309055 0
None
Name [1] 309055 0
None
Address [1] 309055 0
None
Country [1] 309055 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308241 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 308241 0
Ethics committee country [1] 308241 0
Australia
Date submitted for ethics approval [1] 308241 0
Approval date [1] 308241 0
22/02/2021
Ethics approval number [1] 308241 0

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

Contacts
Principal investigator
Name 110038 0
Prof Richard Kanaan
Address 110038 0
Department of Psychiatry
Austin Health
PO Box 5555
145 Studley Road
Heidelberg VIC 3084
Country 110038 0
Australia
Phone 110038 0
+61 3 9496 3351
Fax 110038 0
Email 110038 0
[email protected]
Contact person for public queries
Name 110039 0
Chiranth Bhagavan
Address 110039 0
Department of Psychiatry, Austin Health
145 Studley Road
PO Box 5555
Heidelberg VIC 3084
Country 110039 0
Australia
Phone 110039 0
+61 3 9496 3351
Fax 110039 0
Email 110039 0
[email protected]
Contact person for scientific queries
Name 110040 0
Alexander Bryson
Address 110040 0
Department of Neurology
Austin Health
PO Box 5555
145 Studley Road
Heidelberg VIC 3084
Country 110040 0
Australia
Phone 110040 0
+61 3 94965000
Fax 110040 0
Email 110040 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


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.