Network-Guided Theta Burst Stimulation for Breast Cancer With Chemotherapy-Induced Peripheral Neuropathy: Clinical and fMRI Biomarker Evidence (CIPN TBS)

July 6, 2026 updated by: Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating complication among breast cancer survivors, frequently associated with chronic neuropathic pain that remains inadequately controlled by pharmacological treatments. Emerging evidence suggests that CIPN pain is related to maladaptive reorganization of pain-related brain networks, highlighting the potential of non-pharmacological, brain-based neuromodulation strategies.

Among the variants of theta burst stimulation (TBS), both prolonged constant theta burst stimulation (pcTBS) and intermittent theta burst stimulation (iTBS) have facilitating effects of cortical excitability. The treatment time for pcTBS (1 min and 44 s, 1200 pulses) is much shorter than that of iTBS and traditional repetitive transcranial magnetic stimulation (rTMS); therefore, pcTBS seems to be a promising neuromodulation method for chronic pain and head-to-head comparison between pcTBS and iTBS has never been done before.

The aim of this two-year randomized, cross-over trial project is 1) to compare the effects of pcTBS and iTBS and determine the optimal TBS paradigm for alleviating CIPN pain a sequential focus on distinct cortical targets; 2) to implement a prospectively defined, network-guided framework using fMRI to characterize sensorimotor and pain-related brain connectivity and to examine whether baseline network features and stimulation-induced connectivity changes moderate clinical outcomes.

In Year 1, 20 breast cancer patients with CIPN will be recruited and randomly assigned to two groups: Group I will initially receive pcTBS over M1 for 5 consecutive days and then iTBS over M1 after a 8-week "wash-out" period. Group II will initially receive iTBS over M1 for 5 consecutive days and then pcTBS over M1 after a 8-week "wash-out" period. In year 2, the stimulation target will be changed to dorsolateral prefrontal cortex (DLPFC) to evaluate analgesic effects, and associated brain network changes related to cognitive-affective pain modulation.

MRI-based neuronavigation will be used to ensure precise and reproducible stimulation targeting. Both resting-state and task-based functional MRI will be acquired before stimulation and used prospectively to identify individualized pain-relevant cortical hotspots within predefined anatomical regions (M1 or DLPFC). Resting-state fMRI will be repeated within 24 hours after the final stimulation session to evaluate treatment-related changes in brain networks. Pain intensity measured by the visual analog scale will serve as the primary outcome, with secondary outcomes including Neuropathic Pain Symptom Inventory, Depression Anxiety Stress Scale 21 and pressure pain threshold testing. Primary and secondary outcomes will be evaluated immediately after the last stimulation session and again at 4-week follow-up.

By integrating a clinically efficient trial design with network-informed neuroimaging, this project is expected to provide target-specific evidence for TBS in CIPN pain and to establish a foundation for future precision-guided neuromodulation studies.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • a. breast cancer patients aged between ２０- and 80-years-old with CIPN b. history of receiving chemotherapy including taxane-based neurotoxic agents c. with neuropathic pain, score≥3 in a 0-10 VAS pain scale. d. with fair cognition and can cooperate to evaluate pain severity. e. neither at end-stage cancer nor at the estimated survival time less than 6 months.

Exclusion Criteria:

  • a. brain tumor or history of epilepsy b. intracranial metallic devices, artificial cochleae, pacemakers, or any other metal device c. recent myocardial ischemia or unstable angina d. severe cognitive dysfunction or pregnancy e. injuries or fractures in the part of neuropathic pain

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group I
Group I will initially receive pcTBS over M1 for 5 consecutive days and then iTBS over M1 after a 8-week "wash-out" period
Other: pcTBS
Intermittent TBS (iTBS) applies 2 s of TBS trains repeated every 10 s for a total of 20 cycles (600 pulses, total 190 s) and increases cortical excitability for at least 20 min. pcTBS consisted of three pulses at 50 Hz (i.e., 60 ms) repeated 400 times at intervals of 200 ms (a total of 1,200 pulses in 1 min and 44 s)
Active Comparator: Group 2
Group II will initially receive iTBS over M1 for 5 consecutive days and then pcTBS over M1 after a 8-week "wash-out" period
Other: pcTBS
Intermittent TBS (iTBS) applies 2 s of TBS trains repeated every 10 s for a total of 20 cycles (600 pulses, total 190 s) and increases cortical excitability for at least 20 min. pcTBS consisted of three pulses at 50 Hz (i.e., 60 ms) repeated 400 times at intervals of 200 ms (a total of 1,200 pulses in 1 min and 44 s)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visual analogue pain scale (VAS)
Time Frame: before the first and after the fifth rTMS session in each treatment period
Patients will be instructed to rate their mean daily pain on a 0-100 visual analogue pain scale (VAS).
before the first and after the fifth rTMS session in each treatment period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neuropathic Pain Symptom Inventory
Time Frame: before and after 5-day treatment section
NPSI is comprised of five subscales for assessing the diverse symptoms of neuropathic pain, including burning spontaneous pain (burning), pressing spontaneous pain (pressing), paroxysmal pain (paroxysmal), evoked pain (evoked), and paresthesia/dysesthesia.
before and after 5-day treatment section

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 1, 2026

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

December 31, 2029

Study Registration Dates

First Submitted

July 6, 2026

First Submitted That Met QC Criteria

July 6, 2026

First Posted (Actual)

July 10, 2026

Study Record Updates

Last Update Posted (Actual)

July 10, 2026

Last Update Submitted That Met QC Criteria

July 6, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-IRB011

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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