Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000008426
Ethics application status
Approved
Date submitted
3/12/2024
Date registered
8/01/2025
Date last updated
8/01/2025
Date data sharing statement initially provided
8/01/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
The Transcranial Magnetic stimulation for Chemotherapy-induced pain Study (TMaC Study)
Scientific title
Effectiveness of repetitive Transcranial Magnetic stimulation (rTMS) for pain from chemotherapy-induced peripheral neuropathy (CIPN) measured with the Visual Analogue Scale (VAS) in bowel cancer patients treated with oxaliplatin.
Secondary ID [1] 313513 0
Nil known
Universal Trial Number (UTN)
U1111-1315-2622
Trial acronym
TMaC Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chemotherapy-induced peripheral neuropathy 335944 0
Condition category
Condition code
Neurological 332534 332534 0 0
Other neurological disorders
Cancer 332533 332533 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Repetitive transcranial magnetic stimulation (rTMS) applied by the experimenter on each participant’s pain-associated cortex once a week for a total of four weeks in the Integrative Neurophysiology Lab within the University of Adelaide.
Using a figure-8 coil connected to two Magstim 2002 magnetic stimulators through a Bistim module (Magstim, Dyfed, UK) in a posterior/anterior orientation, the experimenter will apply rTMS over the primary somatosensory cortex (S1), contralateral to the side of the most-affected extremity identified by each patient. S1 in participants will be delimited at a point 2 cm posterior to the hotspot of the first dorsal interosseous (FDI) muscle. The hotspot is defined at the position on S1 with the largest and most consistent response elicited by TMS for the FDI muscle. The intensity of the stimulation will be set to produce a paired-pulse motor evoked potential of 0.5-1.5 mV.
To ensure ensuring intervention fidelity, Neuronavigation system (Brainsight, UK) will be used to enhance the precision and accuracy of TMS by providing real-time guidance to the target brain area.
rTMS intervention consists of 180 paired pulses with the interstimulus interval (ISI) set at 1.5 milliseconds, applied every 5 seconds for a total of 15 minutes. The total duration of each experimental session is estimated to be approximately 1 hour. This includes time for determining the appropriate stimulation intensity and target, administering the rTMS intervention, collecting data, and addressing any potential technical difficulties. Adherence to the intervention will be monitored by recording each session time, duration and the stimulation intensity. Additionally, the application of the rTMS intervention, including the delivery of 180 pulses per session, will be logged and stored on disk for each session.
Intervention code [1] 330087 0
Treatment: Devices
Comparator / control treatment
Control group will receive sham stimulation. A sham coil (identical in appearance as the active coil) will be used, but there are no active pulses delivered through the sham coil.
Control group
Placebo

Outcomes
Primary outcome [1] 340051 0
Pain intensity
Timepoint [1] 340051 0
The primary outcome is measured at baseline, before and after each session, at 8 weeks follow up and at 6 months follow up. The primary timepoint is 8 weeks follow up.
Secondary outcome [1] 442470 0
dysesthesia intensity
Timepoint [1] 442470 0
Baseline, before and after each session, at 8 weeks follow up and at 6 months follow up.
Secondary outcome [2] 442472 0
patients’ perspectives and acceptance of rTMS
Timepoint [2] 442472 0
first follow-up session (i.e. 8 weeks after completion of all treatment sessions)
Secondary outcome [3] 442471 0
CIPN-associated pain
Timepoint [3] 442471 0
beginning of the four intervention sessions, and the two follow-up sessions (i.e. 8 weeks and 6 months after completion of all treatment sessions)

Eligibility
Key inclusion criteria
1. Adults (18 to 85 years old) experiencing CIPN following treatment with oxaliplatin-containing chemotherapy for bowel cancer will be eligible.
2. Patients meet inclusion criteria if they have patient-reported symptoms as moderate or above according to the NCI PRO-CTCAE scale item 39, and 30 mm or greater score on a visual analogue scale (VAS) of pain or dysesthesia intensity.
3. Chemotherapy must have been completed at least 6 months prior to study enrolment.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. participants with a history of epilepsy, implanted cardiac pacemakers, implanted neurostimulators and metallic implants will be excluded (As determined by TMS screening questionnaire will be administered).
2. Any pre-existing neuropathic condition present prior to cancer treatment and any other reasonable cause for a painful neuropathy (such as diabetes or alcohol dependence/misuse) or continuing use of axonal neurotoxic medications.

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)
allocation involves contacting the holder of the allocation schedule who is not involved in the recruitment process and experimentation in the lab
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised block randomisation (blocks of 4) stratified by baseline neuropathy scores and chemotherapy regimen.
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
Efficacy
Statistical methods / analysis
Sample size : Sample size was calculated using Stata, with parameters derived from prior research. An analysis of covariance (ANCOVA) approach was chosen to control for baseline VAS scores, which were predicted to be strongly correlated with post-treatment VAS scores (r = 0.7; Karabis et al., 2016). The minimally clinically meaningful change in VAS scores has been reported to range between 5mm and 20mm (Delgado et al., 2018). In the current study, a 12mm between-group difference in post-treatment VAS scores was considered sufficient to reflect a clinically significant improvement in chronic CIPN-associated pain and to inform clinical practice. The standard deviation was estimated to be 23mm in the rTMS group and 25mm in the sham group, based on the variability in VAS scores observed in pilot rTMS trials for CIPN (Goto et al., 2020, Yan et al., 2023). To achieve 80% power at the 0.05 significance level, a total of 36 participants were needed (18 per arm). The sample size was adjusted to 40 (20 per arm) to account for an anticipated 10% dropout rate, considering each participant will be receive four sessions of treatment each separated by a minimum of one week.

Analysis: Mixed-effects linear regression analyses will be run in Stata to assess main and interaction effects of time and treatment group (sham vs. rTMS) on each of the pain and dysesthesia measurements. The analyses will be adjusted for the corresponding baseline values of each outcome variable, due to strong correlations between the baseline and post-treatment values, to enhance veracity and reliability. Post hoc Bonferroni tests corrected for multiple comparisons will be used to determine where significant differences originate.


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/01/2025
Actual
Date of last participant enrolment
Anticipated
30/03/2026
Actual
Date of last data collection
Anticipated
30/11/2026
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 317962 0
Charities/Societies/Foundations
Name [1] 317962 0
The Hospital Research Foundation
Country [1] 317962 0
Australia
Primary sponsor type
University
Name
The University of Adelaide
Address
Country
Australia
Secondary sponsor category [1] 320298 0
None
Name [1] 320298 0
Address [1] 320298 0
Country [1] 320298 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316634 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 316634 0
Ethics committee country [1] 316634 0
Australia
Date submitted for ethics approval [1] 316634 0
26/07/2024
Approval date [1] 316634 0
31/10/2024
Ethics approval number [1] 316634 0
2024/HRE00199

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

Contacts
Principal investigator
Name 138482 0
Prof Joanne Bowen
Address 138482 0
School of Biomedicine, University of Adelaide, South Australia 5005
Country 138482 0
Australia
Phone 138482 0
+61 8 83131374
Fax 138482 0
Email 138482 0
[email protected]
Contact person for public queries
Name 138483 0
Dr Simran Sidhu
Address 138483 0
School of Biomedicine, University of Adelaide, South Australia, 5005
Country 138483 0
Australia
Phone 138483 0
+61 83131235
Fax 138483 0
Email 138483 0
[email protected]
Contact person for scientific queries
Name 138484 0
Dr Simran Sidhu
Address 138484 0
School of Biomedicine, University of Adelaide, South Australia, 5005
Country 138484 0
Australia
Phone 138484 0
+61 8 83131235
Fax 138484 0
Email 138484 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.