Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000064707
Ethics application status
Approved
Date submitted
2/12/2021
Date registered
20/01/2022
Date last updated
29/05/2024
Date data sharing statement initially provided
20/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase II trial examining the safety and preliminary efficacy of repetitive transcranial magnetic stimulation (rTMS) for people living with multiple sclerosis
Scientific title
A phase II trial examining the safety and preliminary efficacy of repetitive transcranial magnetic stimulation (rTMS) for people living with multiple sclerosis
Secondary ID [1] 305292 0
Nil
Universal Trial Number (UTN)
Trial acronym
TAURUS 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 323595 0
Condition category
Condition code
Neurological 321138 321138 0 0
Multiple sclerosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A low-intensity repetitive transcranial magnetic stimulation (rTMS) for 3 minutes (600 pulses) on each hemisphere of the brain at 50Hz. MBS will be delivered daily, Monday to Friday, for one month (20 sessions). The MBS will be delivered by trained personnel. This will include Clinical Research Fellow and PhD candidates.
Attendance, adherence to intervention and other data will be recorded in REDCap.
Intervention code [1] 321695 0
Treatment: Devices
Comparator / control treatment
Placebo (Sham coil stimulation)
Control group
Placebo

Outcomes
Primary outcome [1] 328929 0
Change in Multiple Sclerosis functional composite score (includes timed 25-foot walk, 9-hole peg test and Symbol Digit Modalities Test) between rTMS and placebo groups
Timepoint [1] 328929 0
From baseline to 4 weeks post randomization. The assessment will be made once at baseline, visit 10 (2 weeks post randomization) and visit 20 (4 weeks post randomization).
Secondary outcome [1] 400887 0
The incidence of treatment emergent adverse events & serious adverse events Examples of known/possible adverse reactions/events include: (a) Expected adverse events headaches, dizziness, tingling of fascial muscles, scalp discomfort (b) Expected serious adverse events
Timepoint [1] 400887 0
from baseline to 4 months post randomization. Adverse events will be recorded at each study visit and their severity & causal relationship assessed by the Principal Investigator AE Severity Assessment Grade 1- Mild, asymptomatic or mild symptoms, clinical or diagnostic observations only; intervention not indicated Grade 2 - Moderate, minimal, local or non-invasive interventions indicated; limiting age appropriate instrumental activity of daily living (ADL) Grade 3 - Severe or medically significant but not immediately life threatening; hospitalisation or prolongation of hospitalisation indicated, disabling, limiting self-care ADL Grade 4- Life threatening consequences; urgent intervention necessary Grade 5 – Death related to AE Causal relationship Related – The AE is known to occur with the study intervention, there is a reasonable possibility that the study intervention caused the AE, or there is a temporal relationship between the study intervention and event. Reasonable possibility means that there is evidence to suggest a causal relationship between the study intervention and the AE. Not Related – There is not a reasonable possibility that the administration of the study intervention caused the event, there is no temporal relationship between the study intervention and event onset, or an alternate aetiology has been established.
Secondary outcome [2] 404635 0
Change in anxiety measured using Hospital anxiety and depression score (HADS)
Timepoint [2] 404635 0
from baseline to 4 months post randomization. This will be assessed three times at Visit 1 (baseline visit), Visit 20 (end of the 4th week) and Visit 21 (3months after visit 20)
Secondary outcome [3] 404636 0
Change in depression measured using Hospital anxiety and depression score (HADS)
Timepoint [3] 404636 0
from baseline to 4 months post randomization. This will be assessed three times at Visit 1 (baseline visit), Visit 20 (end of the 4th week) and Visit 21 (3months after visit 20)
Secondary outcome [4] 404637 0
Change in quality of life assessed by the AQoL-8D’s health state utilities and dimensional scores.
Timepoint [4] 404637 0
from baseline to 4 months post randomization. This will be assessed three times at Visit 1 (baseline visit), Visit 20 (end of the 4th week) and Visit 21 (3months after visit 20)
Secondary outcome [5] 405118 0
Change in fatigue score using the fatigue severity scale (FSS)
Timepoint [5] 405118 0
from baseline to 4 months post randomization. This will be assessed three times at Visit 1 (baseline visit), Visit 20 (end of the 4th week) and Visit 21 (3months after visit 20)
Secondary outcome [6] 405119 0
Change in sleep quality using PSQI and NRS
Timepoint [6] 405119 0
from baseline to 4 months post randomization. This will be assessed three times at Visit 1 (baseline visit), Visit 20 (end of the 4th week) and Visit 21 (3months after visit 20)
Secondary outcome [7] 405120 0
Change between baseline MRI and post-intervention MRI metrics of sham and rTMS intervention groups, including metrics for whole brain, lobe-specific, and lesion locations.
Timepoint [7] 405120 0
From baseline to 4 weeks post randomization. MRI will be performed two times: Within 2 weeks before visit 1 (baseline visit/intervention) and within 2 weeks after visit 20 (week 4).

Eligibility
Key inclusion criteria
Diagnosed of Multiple Sclerosis (MS) by a neurologist,
Has been stable (on or off MS treatment) and relapse free for 6 months
Extended Disability Status Scale (EDSS) between 1.5 and 6
Has capacity to provide informed consent
Able to travel to site every weekday for 4 weeks
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Have metal inside their head or body (i.e. cardiac pacemaker)
Pregnant or intend to become pregnant
Have a history of seizures, epilepsy, serious head trauma*, substance abuse*, stroke, brain surgery, bipolar, mania, claustrophobia or migraines
Have an EDSS < = 1 and > = 6.5
Previously received rTMS therapy
English illiterate** (to enable completion of follow up questionnaires)
Currently involved in another interventional clinical trial

*Note: participants with minor/moderate head trauma, previous substance abuse and/or well controlled or rare migraines may be included on PI discretionary basis, e.g. these conditions are prevalent in the community and may not be clinically significant. **English illiterate participants who can provide a suitable translator/interpreter for the duration of the study (including phone calls, questionnaires, and visits) may be included.

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)
Central randomisation by computer software (REDCap)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (REDCap). Participants were stratified by gender (2:1 to the active rTMS group or SHAM control)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
1. MS Functional composite score (MSFC) will be derived from three components: 1. Symbol Digit Modality (SDMT) scores, 2. Nine-Hole Peg Test (9HPT) scores, and 3. Timed 25 Foot Walk (T25-FW). The MSFC score is calculated as the mean of the z-scores of the three components, with the means and SDs that are required to derive the z-scores for the components taken from a suitable reference population.
Change in z-score will be compared between the rTMS and sham groups by estimating the effect size of the treatment-time interaction term in a linear mixed effects regression model.
2..The incidence of treatment emergent adverse events & serious adverse events. A Fisher’s exact test will be used to compare the proportions of people in the sham group compared to the rTMS group who experience any treatment-emergent AEs.
3. Continuous outcomes (AQol8D, HADS, FSS) will be compared between rTMS and SHAM groups with linear mixed effects regression models. The treatment-time interaction term will be used to estimate the effect of treatment on change in outcomes, as described for the primary outcome.
4. Absolute changes in MRI metrics.Continuous MRI measures will also be analysed with linear mixed effects models. Separate measures for different tissue type and brain regions will be analysed depending on distributions of overall measures.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/06/2022
Actual
24/11/2022
Date of last participant enrolment
Anticipated
31/05/2024
Actual
Date of last data collection
Anticipated
31/08/2024
Actual
Sample size
Target
108
Accrual to date
102
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,WA,VIC
Recruitment hospital [1] 22542 0
John Hunter Hospital - New Lambton
Recruitment hospital [2] 22544 0
Perron Institute for Neurological and Translational Science - Nedlands
Recruitment hospital [3] 22545 0
Launceston General Hospital - Launceston
Recruitment hospital [4] 22546 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [5] 24124 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 37781 0
2305 - New Lambton
Recruitment postcode(s) [2] 37783 0
6009 - Nedlands
Recruitment postcode(s) [3] 37784 0
7250 - Launceston
Recruitment postcode(s) [4] 37785 0
4101 - South Brisbane
Recruitment postcode(s) [5] 39632 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 309663 0
Government body
Name [1] 309663 0
Australian Department of Health - Medical Research Future Fund (MRFF)
Country [1] 309663 0
Australia
Funding source category [2] 309665 0
Government body
Name [2] 309665 0
Australian Department of Health - Emerging Priorities Consumer Driven Research
Country [2] 309665 0
Australia
Funding source category [3] 309666 0
Charities/Societies/Foundations
Name [3] 309666 0
Irene Phelps Charitable Trust
Country [3] 309666 0
Australia
Primary sponsor type
University
Name
University of Tasmania
Address
College of Health and Medicine Research Hub
Office of Research Services, Private Bag 23, Hobart TAS 7001,
Advocate House Level 1, 15 Liverpool Street,
Hobart TAS 7000
Country
Australia
Secondary sponsor category [1] 310682 0
None
Name [1] 310682 0
Nil
Address [1] 310682 0
Nil
Country [1] 310682 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309430 0
Health and Medical Human Research Ethics Committee (HMHREC) University of Tasmania
Ethics committee address [1] 309430 0
Ethics committee country [1] 309430 0
Australia
Date submitted for ethics approval [1] 309430 0
26/11/2021
Approval date [1] 309430 0
18/01/2022
Ethics approval number [1] 309430 0
H0026359
Ethics committee name [2] 311086 0
Hunter New England Human Research Ethics Committee (HNEHREC)
Ethics committee address [2] 311086 0
Ethics committee country [2] 311086 0
Australia
Date submitted for ethics approval [2] 311086 0
01/06/2022
Approval date [2] 311086 0
Ethics approval number [2] 311086 0
2022_ETH01012

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

Contacts
Principal investigator
Name 114138 0
Prof Bruce Taylor
Address 114138 0
Menzies Institute for Medical Research, University of Tasmania
Medical Science Precinct, Level 3
19 Liverpool St, Hobart, TAS 7000
Country 114138 0
Australia
Phone 114138 0
+61 36226 7765
Fax 114138 0
Email 114138 0
[email protected]
Contact person for public queries
Name 114139 0
Kate Probert
Address 114139 0
Menzies Institute for Medical Research, University of Tasmania
Medical Science Precinct, Level 3
19 Liverpool St, Hobart, TAS 7000
Country 114139 0
Australia
Phone 114139 0
+61 36226 7746
Fax 114139 0
Email 114139 0
[email protected]
Contact person for scientific queries
Name 114140 0
Vincent Chigozie Ezegbe
Address 114140 0
Menzies Institute for Medical Research, University of Tasmania
Medical Science Precinct, Level 3
19 Liverpool St, Hobart, TAS 7000
Country 114140 0
Australia
Phone 114140 0
+61 36226 4236
Fax 114140 0
Email 114140 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.