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

NCT07695415 | Not Yet Recruiting

• 1 other identifier: 15-IRB011
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

CIPN - Chemotherapy-Induced Peripheral Neuropathy; Breast Cancer

Keywords

CIPN; breast cancer; theta burst stimulation

Outcome Measures

Primary Outcomes (1)

• Visual analogue pain scale (VAS)

  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 Outcomes (1)

• Neuropathic Pain Symptom Inventory

  before and after 5-day treatment section

Study Arms (2)

Group I

EXPERIMENTAL

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

Group 2

ACTIVE COMPARATOR

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

Interventions

pcTBS OTHER

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)

Group 2; Group I

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation: lead

Study Sites (1)

Taipei Tzuchi Hospital

New Taipei City, Taiwan

Location

Related Links

• doi: 10.1177/20503121231209088

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Yi-shiung Horng, MD., PhD.

CONTACT

886-2-66289779; yshorng2015@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 10, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)