Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000492459p
Ethics application status
Submitted, not yet approved
Date submitted
2/05/2025
Date registered
21/05/2025
Date last updated
21/05/2025
Date data sharing statement initially provided
21/05/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Study of Transcranial Magnetic Stimulation Enhanced Physiotherapy for people with Functional Movement Disorder.
Scientific title
A phase 2a, single arm study of Transcranial Magnetic Stimulation Enhanced Physiotherapy to Restore Movement Agency and Walking Independence in people with Functional Movement Disorder.
Secondary ID [1] 314014 0
None
Universal Trial Number (UTN)
U1111-1318-9170
Trial acronym
STEP-FMD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Functional Movement Disorder 336751 0
Condition category
Condition code
Neurological 333242 333242 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single session of transcranial magnetic stimulation (TMS) and distal limb pressure feedback will be used immediately prior to a specialist physiotherapy session.

Participants will receive up to 25 single-pulse stimulations of TMS per affected hemisphere, delivered by a researcher. Stimulations are delivered in blocks of 3 or 4, at 100% maximum stimulator output (MSO) over each affected hemispheres primary motor cortex, while the participant attempts voluntary movement of their affected lower limb. Distal limb pressure from a researcher's hands will be used concurrently with stimulations. Contemporary neuroscientific explanations of Functional Movement Disorder (FMD) and educational components will be delivered throughout. Explanations will include using the ‘software-hardware’ analogy and a conversation about using TMS as a way of boosting the brain signal to their affected limb(s). Participants will be shown their TMS traces, identifying motor evoked potentials (MEPs). A researcher will explain basic features of the TMS traces and relate these to the participant's individual presentation. TMS and discussions are expected to take 30 minutes.

Immediately following TMS, participants will start a single individualised physiotherapy session, delivered face-to-face by a neurological physiotherapist with at least 10 years experience. Physiotherapy will use established FMD treatment principles and will be delivered in a gym or clinic. FMD physiotherapy treatment-based principles include: building trust before challenging the patient, projecting confidence, creating an expectation for improvement, limiting ‘hands-on’ treatment and focusing attention away from impairment and towards function, by use of distraction. Examples include conversational distraction, or throwing and catching a rugby ball, while standing. The physiotherapy session may last for a maximum of 3 hours total, and will include rest periods as needed. Family or supporters will be encouraged to join in the treatment session and will be included in educational moments. Participants will be encouraged to use their individualised distraction strategies after the session. Physiotherapy sessions may also include discussion of key topics: beliefs about symptoms and diagnosis, fatigue, distraction, self-management principles, and how to manage an unexpected dramatic recovery.

To meet the intervention protocol, participants must have: a minimum of 10 stimulations above 70% MSO, with pressure feedback, per side affected; and a minimum of 20 minutes of time spent active during physiotherapy interventions.
Intervention code [1] 330593 0
Treatment: Devices
Intervention code [2] 330594 0
Rehabilitation
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 340809 0
The difference between pre- and post-intervention total Tinetti Performance Oriented Mobility Assessment (Tinetti POMA) score.
Timepoint [1] 340809 0
Pre-Intervention and immediately post-intervention.
Secondary outcome [1] 445113 0
Change in functional movement symptoms will be calculated as the difference between pre- and post-intervention Simplified Functional Movement Disorders Rating Scale (S-FMDRS) score.
Timepoint [1] 445113 0
Pre-Intervention and immediately post-intervention.
Secondary outcome [2] 445411 0
Change in participant reported severity of all functional motor symptoms will be calculated as the difference between pre-intervention and 12-week follow up, assessed using a Likert Scale.
Timepoint [2] 445411 0
Pre-intervention and 12-weeks post-intervention.
Secondary outcome [3] 445412 0
Change in participant reported overall severity of functional motor symptoms will be calculated as the difference between pre-intervention and 12-week follow up, assessed using a Likert Scale.
Timepoint [3] 445412 0
Pre-intervention and 12-weeks post-intervention.
Secondary outcome [4] 445414 0
Change in overall lower limb strength will be calculated as the difference between total pre- and post-intervention strength grades for out of 40.
Timepoint [4] 445414 0
Pre-intervention and immediately post-intervention.
Secondary outcome [5] 445415 0
Participant self-rated improvement will be assessed using the Clinical Global Impression – Improvement scale (CGI-I). The percentage of participants in each rating category will be calculated at each follow-up timepoint.
Timepoint [5] 445415 0
Immediately post-intervention, 1-week, 4-weeks, and 12-weeks post-intervention.
Secondary outcome [6] 445611 0
Participant walking independence will be assessed using the Functional Ambulation Categories (FAC). The percentage of participants who are independent (FAC score >3) will be calculated at each follow-up timepoint.
Timepoint [6] 445611 0
Immediately post-intervention, 1-week, 4-weeks, and 12-weeks post-intervention.
Secondary outcome [7] 445874 0
Change in sense of agency will be calculated as the difference between pre-intervention and 12-week follow up Sense of Agency Scale (SoAS) scores.
Timepoint [7] 445874 0
Pre-intervention and 12-weeks post intervention.
Secondary outcome [8] 445875 0
Change in quality of life will be calculated as the difference between pre-intervention and 12-week follow up Short-Form 12 (SF-12) survey scores.
Timepoint [8] 445875 0
Pre-intervention and 12-weeks post intervention.
Secondary outcome [9] 445876 0
The frequency and type of adverse events will be recorded at each follow up timepoint. Adverse events may include reactions to transcranial magnetic stimulation, falls, pain or worsening of functional symptoms, as defined by the study protocol.
Timepoint [9] 445876 0
Every hour during the intervention, and at 1-week, 4-weeks, and 12-weeks post-intervention.
Secondary outcome [10] 446213 0
Change in upper limb function will be calculated as the difference between pre- and post-intervention Box and Blocks Test score.
Timepoint [10] 446213 0
Pre-intervention and immediately post-intervention.
Secondary outcome [11] 447068 0
Psychosocial effects of intervention will be assessed using a custom survey with 8 statements regarding their relationships, identity, emotions and activities of daily living. They will indicate their level of agreement using a 5-point Likert scale for each statement and a total score will be calculated out of 40 points.
Timepoint [11] 447068 0
1-week post-intervention
Secondary outcome [12] 447069 0
Semi-structured interviews will explore participant experiences of the intervention and effects on biopsychosocial aspects of wellbeing.
Timepoint [12] 447069 0
4-weeks post-intervention.
Secondary outcome [13] 447499 0
Perceived comfort with the intervention will be assessed using a custom survey.
Timepoint [13] 447499 0
1-week post-intervention.
Secondary outcome [14] 447500 0
Perceived tolerability with the intervention will be assessed using a custom survey.
Timepoint [14] 447500 0
1-week post-intervention.
Secondary outcome [15] 447501 0
Perceived safety with the intervention will be assessed using a custom survey.
Timepoint [15] 447501 0
1-week post-intervention.
Secondary outcome [16] 447502 0
Participant satisfaction with the intervention will be assessed using a custom survey.
Timepoint [16] 447502 0
1-week post-intervention.

Eligibility
Key inclusion criteria
i. At least 18 years old
ii. Clinically established diagnosis of functional neurological disorder (or equivalent term)
iii. Investigations were accepted as complete by the patient and treating physician
iv. No contraindications to non-invasive brain stimulation (NIBS) as determined using the TMS safety screening checklist
v. Functional Ambulation Category score <3 without the use of a walking aid for more than 4 out of the last 7 days
vi. Lower limb functional weakness
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i. Medical instability precluding safe participation in physiotherapy as determined by the study physician
ii. Cognitive or communication impairment precluding informed consent
iii. Untreated and severe psychiatric illness affecting their ability to safely participate, determined by the study physician
iv. Coexisting non-FND neurological or musculoskeletal impairments restricting walking independence
v. Pain or fatigue limiting walking, determined by an average pain or fatigue rating of >4/10 over the previous week

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
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Sample size:
a. The primary outcome measure is the change in the Tinetti POMA score between pre-intervention and immediately after the intervention. The minimum detectable change for this scale is 4.2 points for older adults and 6 points for chronic stroke patients. The minimal clinically important difference for this scale is 10.83 for chronic stroke patients and mean change for participants who rated their improvement as ‘very improved’ was 10.77 ± 1.23 points.
b. With no available literature for FMD, we estimated the extent of expected improvement for the intervention based on five clinical cases previously treated with TMS-enhanced physiotherapy. All five made greater than or equal to a 12 point improvement in Tinetti POMA immediately after the intervention. This magnitude of improvement relates to an effect size of approximately 2.0.
c. Sample size was calculated based on a conservative estimate of an effect size of 1.0. A sample of 13 participants is required for a one-tailed comparison with a = 0.05 and 1-ß = 95%. A long duration of symptoms is considered a poor prognostic feature for people with FMD. Treatment effects may differ depending on the chronicity of functional symptoms, with those greater than 12 months being potentially less responsive. Therefore, we aim to recruit 13 participants with symptom durations greater than 12 months and 13 participants with symptom durations less than 12 months. Allowing for 4 participants to be lost to follow-up, we therefore plan to recruit up to 30 participants.

Primary outcome analysis:
The difference between pre-intervention and immediately post-intervention Tinetti POMA scores will be calculated for all participants. If the differences are normally distributed, a one-sample t test against a difference of zero will be used. A Cohen’s d effect size will be estimated with 95% confidence intervals.

If the differences are not normally distributed a Wilcoxon signed-rank test for related samples will be used to compare pre-intervention and immediately post-intervention Tinetti POMA scores.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/06/2025
Actual
Date of last participant enrolment
Anticipated
31/05/2027
Actual
Date of last data collection
Anticipated
6/09/2027
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment outside Australia
Country [1] 26907 0
New Zealand
State/province [1] 26907 0

Funding & Sponsors
Funding source category [1] 318518 0
Government body
Name [1] 318518 0
Health Research Council of New Zealand
Country [1] 318518 0
New Zealand
Primary sponsor type
University
Name
Waipapa Taumata Rau, University of Auckland
Address
Country
New Zealand
Secondary sponsor category [1] 320910 0
None
Name [1] 320910 0
Address [1] 320910 0
Country [1] 320910 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 317208 0
Northern A Health and Disability Ethics Committee 
Ethics committee address [1] 317208 0
Ethics committee country [1] 317208 0
New Zealand
Date submitted for ethics approval [1] 317208 0
28/04/2025
Approval date [1] 317208 0
Ethics approval number [1] 317208 0

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

Contacts
Principal investigator
Name 140074 0
Prof Cathy Stinear
Address 140074 0
Faculty of Medical and Health Sciences, University of Auckland, 28 Park Ave, Grafton, Auckland, 1023
Country 140074 0
New Zealand
Phone 140074 0
+64 099233779
Fax 140074 0
Email 140074 0
[email protected]
Contact person for public queries
Name 140075 0
Cathy Stinear
Address 140075 0
Faculty of Medical and Health Sciences, University of Auckland, 28 Park Ave, Grafton, Auckland, 1023
Country 140075 0
New Zealand
Phone 140075 0
+64 099233779
Fax 140075 0
Email 140075 0
[email protected]
Contact person for scientific queries
Name 140076 0
Cathy Stinear
Address 140076 0
Faculty of Medical and Health Sciences, University of Auckland, 28 Park Ave, Grafton, Auckland, 1023
Country 140076 0
New Zealand
Phone 140076 0
+64 099233779
Fax 140076 0
Email 140076 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.