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Trial registered on ANZCTR


Registration number
ACTRN12622000525785
Ethics application status
Approved
Date submitted
25/03/2022
Date registered
4/04/2022
Date last updated
24/03/2024
Date data sharing statement initially provided
4/04/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The effectiveness and acceptability of Breathing Control Training (BCT) for Functional Seizures (FS)
Scientific title
Breathing Control Training (BCT) as a Treatment for Functional Seizures (FS) - a multi-centre, assessor blinded, randomised controlled efficacy and acceptability trial
Secondary ID [1] 306768 0
NHMRC APP2000376
Universal Trial Number (UTN)
Trial acronym
BREATHS trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Functional Seizures 325783 0
Condition category
Condition code
Mental Health 323121 323121 0 0
Other mental health disorders
Neurological 323175 323175 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Breathing Control Training (BCT) teaches appropriate rate and depth of breathing and the development of a pattern of breathing appropriate to a person's current physical activity level. The elimination of dysfunctional breathing patterns, including hyperinflation and hyperventilation, is discussed. Diaphragmatic breathing is taught, and emphasis is placed on calm, slow, nasal expiration. Education on stress responses and their interactions with breathing patterns is given. The integration of appropriate breathing and relaxation techniques into daily living activities is encouraged. Initially exercises are taught in a semi-recumbent position, progressing to sitting, then standing, then during everyday activities. Finally, the integration of breathing and relaxation techniques into speech is taught and practiced.

In this project, BCT will be delivered by a respiratory physiotherapist with specific training in this technique at the participant’s primary care hospital, or via Telehealth if required. The physiotherapist will conduct a 60min initial session with the participant (one-on-one) and a 30min refresher (‘booster’) session (one-on-one) 4-weeks later. Participants will be encouraged to practice the learnt BCT techniques daily (5-10 minutes, twice daily) and record their adherence in a calendar style diary. The diary will be be reviewed by the physiotherapist at the booster session and compliance recorded in the participant's case report form, as well if they attended both treatment sessions (initial and booster).
Intervention code [1] 323220 0
Treatment: Other
Comparator / control treatment
The control condition, Befriending, is specifically designed to be the control intervention for clinical trials of psychology-based or ‘talking’ therapies. It offers the same clinician contact, and involves meeting and talking with the participant in a supportive, friendly, but non-directive manner. Topics of discussion should be those that are interesting to the participant, and ones that do not bring up negative associations or conflict, for example, talking about movies they like, pets, holidays, cooking, sport, music etc. Befriending has been manualised and its outcomes formally assessed to allow it to serve as a theoretically justified ’placebo’ arm. It has become the standard control arm in therapy trials for mental health, as it matches for expectancy, acceptability, enjoyment and engagement, while delivering no specific benefit on most outcomes.

In this project, the Befriending will be administered by the same clinicians (physiotherapists) at intervals and duration matching the BCT sessions (60min initial one-on-one session and 30min one-on-one 'booster' session 4-weeks later, conducted at the participant's primary care site). The physiotherapist will record the date of attendance (or if the participant failed to attend) for both Befriending sessions in the participant's case report form.
Control group
Active

Outcomes
Primary outcome [1] 330888 0
Participant self-reported seizure remission, defined as seizure frequency of zero in the preceding 4-weeks.
Timepoint [1] 330888 0
Measured 12-weeks post initial treatment session of BCT/Befriending
Secondary outcome [1] 407929 0
Change in hyperventilation from baseline, measured by the Nijmegen scale of hyperventilation
Timepoint [1] 407929 0
Nijmegen scale of hyperventilation provided at baseline, and 4-weeks, 12-weeks & 24-weeks post the initial treatment (BCT/Befriending) session
Secondary outcome [2] 407946 0
Acceptability of BCT assessed by a tailored participant self-report questionnaire
Timepoint [2] 407946 0
Provided after attending the ‘booster’ BCT treatment session approx. 4-weeks after their baseline session
Secondary outcome [3] 407947 0
Changes in healthcare utilisation from baseline, measured via a tailored self-report resource use questionnaire (RUQ), as well as changes in health service use obtained from Services Australia (the latter for consenting participants based in Australia) and The Centre for Victorian Data Linkage (CVDL) (for consenting Victorian participants), assessed as a composite secondary outcome where possible.
Timepoint [3] 407947 0
The RUQ will be provided to participants at baseline, and 12-weeks & 24-weeks post the initial treatment (BCT/Befriending) session. Services Australia data will be requested for the period 12-weeks prior to the participant's randomisation into the trial until the final assessment date (24-weeks post the initial BCT/Befriending treatment session).
Secondary outcome [4] 407948 0
Changes in quality of life from baseline, measured by the Assessment of Quality of Life Eight Dimension (AQoL 8D)
Timepoint [4] 407948 0
Provided at baseline, and 4-weeks, 12-weeks & 24-weeks post the initial treatment (BCT/Befriending) session.
Secondary outcome [5] 407949 0
Changes in depression and anxiety symptoms from baseline, measured by the Hospital Anxiety and Depression Scale (HADS)
Timepoint [5] 407949 0
Provided at baseline, and 4-weeks, 12-weeks & 24-weeks post the initial treatment (BCT/Befriending) session.
Secondary outcome [6] 407952 0
Changes in occupational and social functioning from baseline, measured by the Work and Social Adjustment Scale (WSAS)
Timepoint [6] 407952 0
Provided at baseline, and 4-weeks, 12-weeks & 24-weeks post the initial treatment (BCT/Befriending) session.
Secondary outcome [7] 407953 0
Safety of BCT assessed by the occurrence of adverse events (AEs). From the investigator's own pilot data (unpublished at present), and randomised-controlled trials of breathing exercises for asthma, BCT’s excellent safety and tolerability profile is evident. Nonetheless, AEs will be reviewed and monitored throughout the trial to further explore BCT’s safety profile in Functional Seizures specifically. Thus, participant's will be asked the following questions:
-If they have received a diagnosis of a new medical condition/disease since baseline
-If they have experienced a worsening in a pre-existing medical condition since baseline
-If any new symptoms have occurred since baseline
-If they have been informed of any abnormal laboratory findings which are identified after randomisation into the trial
Timepoint [7] 407953 0
AEs will be reviewed 4-weeks, 12-weeks and 24-weeks post the initial treatment (BCT/Befriending) session via an online self-report questionnaire. After reviewing their responses, the research assistant will contact the participant if they require any further information (for example, clarifying onset, duration, severity of the AE) before reporting all AEs to an independent Data and Safety Monitoring Board (DSMB) comprising an epileptologist, psychiatrist and researcher/statistician for review.

Eligibility
Key inclusion criteria
i) 16 years of age or above
ii) Able to provide written, informed consent
iii) Diagnosis of Functional Seizures (FS; clinically established by an Epileptologist)
iv) Self-reported FS frequency of at least 2 per month
v) English sufficient to complete questionnaires and understand the treatment intervention
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i) Co-morbid epilepsy (supported by minimum 24 hours of video-EEG)
ii) Currently engaging in other breathing therapy treatments/clinical trials

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be allocated sequentially following the randomisation schedule. The randomisation schedule will be stored by an independent statistician, as well as on REDCap, with access permitted to the trial physiotherapists providing the treatment (and who are unblinded during the trial).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be individually randomised 1:1 to the BCT or the control arm (Befriending). A randomly permuted block randomisation list will be computer-generated by an independent statistician, stratified by site and hyperventilation (Nijmegen score >23 vs <22).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A formal detailed statistical analysis plan for the study will be written prior to unblinding of the database. All analyses will be performed on an intention-to-treat basis and include all randomised participants. Analysis and reporting of the findings may take between 3-6 months.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/01/2023
Actual
20/02/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
220
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 22039 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 22040 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [3] 22041 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [4] 22042 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 37153 0
3004 - Melbourne
Recruitment postcode(s) [2] 37152 0
3050 - Parkville
Recruitment postcode(s) [3] 37151 0
3065 - Fitzroy
Recruitment postcode(s) [4] 37150 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 24685 0
New Zealand
State/province [1] 24685 0
Christchurch

Funding & Sponsors
Funding source category [1] 311107 0
Government body
Name [1] 311107 0
National Health & Medical Research Council (NHRMC)
Country [1] 311107 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
Parkville VIC 3010
Country
Australia
Secondary sponsor category [1] 312442 0
None
Name [1] 312442 0
Address [1] 312442 0
Country [1] 312442 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310637 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 310637 0
Level 8, Harold Stokes Building
Austin Hospital
145 Studley Rd
Heidelberg VIC 3084
Ethics committee country [1] 310637 0
Australia
Date submitted for ethics approval [1] 310637 0
16/02/2022
Approval date [1] 310637 0
27/06/2022
Ethics approval number [1] 310637 0

Summary
Brief summary
We do not understand very clearly what causes Functional Seizures (FS; also known as Non-Epileptic Seizures, or Psychogenic Non-epileptic Seizures) or how to treat them. Previous research suggests that rapid breathing (called hyperventilating) can provoke an episode in some people who have FS. We think that if these people could learn to control their breathing so that they didn’t breathe too quickly this might stop them having seizures. We have tested this on a few people with FS by teaching them something called Breathing Control Training (or ‘BCT’ for short) and found that most of their seizures either stopped or became much less frequent.

BCT is a treatment provided by physiotherapists for people with asthma so they can manage their hyperventilation symptoms, but we want to see if it works for people who experience Functional Seizures (FS). In this research project, we will provide BCT, or a comparison treatment known as 'Befriending', to 220 people with FS so we can determine how many people BCT works for, and which people it does help (so we know who to recommend the treatment to in future). We will also assess if BCT is safe for FS (i.e. does it cause any side effects); if it is acceptable (i.e. do people like it, and find it easy to implement); and if it is an affordable treatment option for people with FS.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 118350 0
Prof Richard Kanaan
Address 118350 0
Level 10, Lance Townsend Building
Austin Health
145 Studley Rd
Heidelberg VIC 3084
Country 118350 0
Australia
Phone 118350 0
+61 394963351
Fax 118350 0
Email 118350 0
richard.kanaan@unimelb.edu.au
Contact person for public queries
Name 118351 0
Prof Richard Kanaan
Address 118351 0
Level 10, Lance Townsend Building
Austin Health
145 Studley Rd
Heidelberg VIC 3084
Country 118351 0
Australia
Phone 118351 0
+61 394963351
Fax 118351 0
Email 118351 0
richard.kanaan@unimelb.edu.au
Contact person for scientific queries
Name 118352 0
Prof Richard Kanaan
Address 118352 0
Level 10, Lance Townsend Building
Austin Health
145 Studley Rd
Heidelberg VIC 3084
Country 118352 0
Australia
Phone 118352 0
+61 394963351
Fax 118352 0
Email 118352 0
richard.kanaan@unimelb.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Non-identifiable participant self-report questionnaire data, and clinical characteristics (for those participants who provide specific consent for data sharing).
When will data be available (start and end dates)?
Immediately following publication; no end date determined
Available to whom?
Projects that have obtained approval from a registered HREC committee
Available for what types of analyses?
Analyses that have obtained approval from a registered HREC committee
How or where can data be obtained?
Please contact the PI, Prof Richard Kanaan via email: richard.kanaan@unimelb.edu.au


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15567Clinical study report  richard.kanaan@unimelb.edu.au



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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