CompletedPhase 2ACTRN12621000578808

Psilocybin-assisted physiotherapy for refractory Functional Neurological Disorder

Efficacy and tolerability of psilocybin-assisted physiotherapy on motor symptoms in refractory Functional Neurological Disorder

Sponsor

Austin Health

Enrollment

24 participants

Start Date

May 15, 2024

Study Type

Interventional

Conditions

Functional neurological disorder

Summary

Functional Neurological Disorder is a common neuropsychiatric condition which is often chronic and results in debilitating symptoms such as weakness or sensory impairment. The symptoms of Functional Neurological Disorder are not caused by structural abnormalities within the brain or nervous system, and unfortunately no effective therapy currently exists. It is thought that drugs belonging to a class known as psychedelics, when administered in conjunction with a physiotherapy regime, may be particularly effective in the treatment of Functional Neurological Disorder but this therapeutic intervention has not previously been investigated in a clinical trial. Therefore, this study will assess the safety and obtain preliminary evidence for efficacy of psilocybin-assisted physiotherapy for patients with refractory motor Functional Neurological Disorder.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 65 Yearss

Inclusion Criteria3

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.

Exclusion Criteria16

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.
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

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Interventions

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).