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Trial registered on ANZCTR


Registration number
ACTRN12617000487314
Ethics application status
Approved
Date submitted
28/03/2017
Date registered
4/04/2017
Date last updated
10/07/2019
Date data sharing statement initially provided
10/07/2019
Date results information initially provided
10/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Theta Burst Stimulation in fibromyalgia
Scientific title
A double-blind randomized sham-controlled trial to evaluate the effect of prefrontal Theta Burst Stimulation on severity and impact of pain in patients with fibromyalgia
Secondary ID [1] 291109 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fibromyalgia 301936 0
Condition category
Condition code
Musculoskeletal 301589 301589 0 0
Other muscular and skeletal disorders
Neurological 302241 302241 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Theta Burst Stimulation (TBS).

Participants will undergo 32 treatment sessions across 4 weeks administered by a research nurse. Each TBS procedure will take approximately 3 minutes and you will complete two TBS treatments at each visit (total of 6 minutes of TBS treatment per visit, 15 minutes between each treatment). During the initial two weeks of treatment, participants will attend daily (Monday-Friday) treatment. During the final two weeks of treatment, participants will attend treatment on Mondays, Wednesdays and Fridays only.

TBS will be administered with a NeuroSoft-MS/D or Magventure Magpro magnetic stimulator using a figure-of-8 coil, dependent on patient scheduling. Prior to the commencement of rTMS treatment, single pulse TMS will be used to measure the resting motor thresholds (RMT) in all subjects using standard methods. The RMT is used to determine the intensity of the rTMS treatment and is a means of tailoring the stimulus intensity for each participant.

Participants will be randomly allocated to receive either active or sham TBS via a computer generated sequence by a study investigator who is not involved in treatment or assessment. In active TBS treatment, participants will receive 3-pulse 50Hz bursts applied at 5Hz. Stimulation intensity will be set at up to 120% RMT and will be applied to the left dorsolateral prefrontal cortex.

To assess fidelity of blinding we will be conducting blinding questionnaires with participants at the end of their treatment..The above protocol is in compliance with current published TBS safety guidelines.
Intervention code [1] 297098 0
Treatment: Devices
Comparator / control treatment
Participants allocated to the sham condition will be administered sham TBS that will be identical to the active condition (described above) except no stimulation will be applied.
Control group
Placebo

Outcomes
Primary outcome [1] 300995 0
Change in severity and impact of pain as measured by the Brief Pain Inventory (Short-form).
Timepoint [1] 300995 0
Baseline versus 4 weeks versus 8 weeks
Primary outcome [2] 302691 0
Multifaceted Fatigue Inventory
Timepoint [2] 302691 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [1] 331360 0
A Numerical Pain Rating Scale of pain intensity and pain unpleasantness (NPRS 0-10)
Timepoint [1] 331360 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [2] 331361 0
Short-Form McGill Pain Questionnaire
Timepoint [2] 331361 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [3] 331362 0
Self-reported health assessed by Short-Form 36 Version 2
Timepoint [3] 331362 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [4] 331363 0
Fibromyalgia Impact Questionnaire
Timepoint [4] 331363 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [5] 331364 0
Beck Depression Inventory-II
Timepoint [5] 331364 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [6] 331365 0
Beck Anxiety Inventory
Timepoint [6] 331365 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [7] 331366 0
State-Trait Anxiety Index
Timepoint [7] 331366 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [8] 331367 0
Multifaceted Fatigue Inventory
Timepoint [8] 331367 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [9] 331368 0
Pain Catastrophisation Index
Timepoint [9] 331368 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [10] 331369 0
Depression, Anxiety, and Stress Scale 21
Timepoint [10] 331369 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [11] 331370 0
Posttraumatic Stress Disorder Checklist
Timepoint [11] 331370 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [12] 331371 0
Medical Outcomes Study Sleep Outcomes
Timepoint [12] 331371 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [13] 331372 0
Pittsburg Sleep Quality Index
Timepoint [13] 331372 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [14] 331373 0
Pain Self-Efficacy Questionnaire
Timepoint [14] 331373 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [15] 331374 0
Pain Vigilance and Awareness Scale
Timepoint [15] 331374 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [16] 331375 0
Pain Anxiety Symptom Scale
Timepoint [16] 331375 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [17] 331376 0
Pain Beliefs and Perceptions Inventory
Timepoint [17] 331376 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [18] 331377 0
Adverse Events will be recorded via self report. This may include head-ache or neck-ache, and, although very unlikely, seizure.
Timepoint [18] 331377 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [19] 331380 0
Patient Global Impression of Change
Timepoint [19] 331380 0
End of treatment course (week 4) and 8 weeks
Secondary outcome [20] 333243 0
Cortical function via Transcranial magnetic stimulation (TMS) with concurrent electroencephalogram (EEG) recording (TMS-EEG)
Timepoint [20] 333243 0
Baseline versus 4 weeks versus 8 weeks
Secondary outcome [21] 336761 0
Childhood Trauma Questionnaire (CTQ) and the Life Events Checklist (LEC)
Timepoint [21] 336761 0
Baseline vs 4 weeks vs 8 weeks

Eligibility
Key inclusion criteria
Inclusion Criteria: patients will be included if they:
- have a current diagnosis of fibromyalgia
- aged between 18 and 75 years
- have had no increase or initiation of new medication therapy in the four weeks prior to study screen
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria: Participants who:
- Patients who have an unstable medical condition, neurological disorder or any history of seizure disorder or are currently pregnant or lactating
- The presence of metal anywhere in the head, except the mouth, which may interfere with the magnetic field
- Have a current DSM-V diagnosis of Substance Abuse or Dependence disorder, or another psychiatric condition. This excludes depression, PTSD or anxiety unless they are the primary disorder (i.e. fibromyalgia is not the primary disorder).

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 295550 0
University
Name [1] 295550 0
Monash University
Address [1] 295550 0
Monash Alfred Psychiatry Research Center,
Level 4, 607 St Kilda Road
Melbourne 3004 VIC
Country [1] 295550 0
Australia
Primary sponsor type
Individual
Name
Dr Bernadette Fitzgibbon
Address
Monash Alfred Psychiatry Research Center,
Level 4, 607 St Kilda Road
Melbourne 3004 VIC
Country
Australia
Secondary sponsor category [1] 294372 0
None
Name [1] 294372 0
Address [1] 294372 0
Country [1] 294372 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296870 0
Alfred Health Ethics Committee
Ethics committee address [1] 296870 0
55 Commercial Rd, Melbourne VIC 3004

Ethics committee country [1] 296870 0
Australia
Date submitted for ethics approval [1] 296870 0
01/02/2017
Approval date [1] 296870 0
23/03/2017
Ethics approval number [1] 296870 0
33/17
Ethics committee name [2] 297352 0
Monash Ethics
Ethics committee address [2] 297352 0
Monash Research Office. Monash Research Office Chancellery Building D 26 Sports Walk Monash University, Clayton, Victoria 3800.
Ethics committee country [2] 297352 0
Australia
Date submitted for ethics approval [2] 297352 0
30/03/2017
Approval date [2] 297352 0
30/03/2017
Ethics approval number [2] 297352 0
8790

Summary
Brief summary
The proposed study aims to conduct a double-blind, randomized, sham-controlled proof of principle trial to establish the efficacy of Theta Burst Stimulation (TBS) treatment in fibromyalgia. Fibromyalgia and related disorders present a substantial health problem, with current treatments limited in their efficacy and associated with a number of side effects. This study will explore for the first time in fibromyalgia a novel non-pharmaceutical intervention, TBS; a non-invasive brain stimulation method. TBS is a powerful new alternative to standard non-invasive brain stimulation methods as it can be applied in a much more time efficient manner and may result in greater clinical benefit. If successful, the application of this method for fibromyalgia may be applicable to related disorders such as Chronic Fatigue Syndrome.

This is a randomised sham-controlled trial study, in which 52 participants with a diagnosis of fibromyalgia will be recruited. Participants will be randomised into one of two conditions- (1) Active TBS condition and (2) Sham (or ‘placebo’) TBS condition. Participants will have two weeks of twice daily stimulation followed by a tapered two week dose of twice daily treatments on Monday, Wednesday and Friday only. Participants will be asked to a number of self-report questionnaires at baseline, at the end of each treatment week (weeks 1-4) and at the 1 month follow up appointment, as well as will undergo the collection of neurobiological data (TMS-EEG) at baseline, end of week 4 and follow-up.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72286 0
Dr Bernadette Fitzgibbon
Address 72286 0
Monash Alfred Psychiatry Research Centre
Level 4, 607 St Kilda Road
Melbourne VIC 3004
Country 72286 0
Australia
Phone 72286 0
+61 3 9076 9860
Fax 72286 0
Email 72286 0
bernadette.fitzgibbon@monash.edu
Contact person for public queries
Name 72287 0
Dr Bernadette Fitzgibbon
Address 72287 0
Monash Alfred Psychiatry Research Centre
Level 4, 607 St Kilda Road
Melbourne VIC 3004
Country 72287 0
Australia
Phone 72287 0
+61 3 9076 9860
Fax 72287 0
Email 72287 0
bernadette.fitzgibbon@monash.edu
Contact person for scientific queries
Name 72288 0
Dr Bernadette Fitzgibbon
Address 72288 0
Monash Alfred Psychiatry Research Centre
Level 4, 607 St Kilda Road
Melbourne VIC 3004
Country 72288 0
Australia
Phone 72288 0
+61 3 9076 9860
Fax 72288 0
Email 72288 0
bernadette.fitzgibbon@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We do not have ethical approval to share patient data.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary