TENS and Compression for Established Oxaliplatin-Induced Peripheral Neuropathy

NCT07409987 | Completed

• 1 other identifier: CumhuriyetU-SBE-SÖ-1
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

Chemotherapy-induced peripheral neuropathy is a clinically important adverse effect of oxaliplatin-based chemotherapy that may cause sensory symptoms, neuropathic pain, functional limitations, and reduced quality of life. This randomized, open-label, four-arm parallel-group study evaluated the comparative effects of transcutaneous electrical nerve stimulation (TENS), compression, sequential TENS followed by compression, and usual care in 140 adults with metastatic gastrointestinal cancer who developed Grade 2 or higher chemotherapy-induced peripheral neuropathy after the first cycle of oxaliplatin-based chemotherapy. Participants were allocated in a 1:1:1:1 ratio. The primary outcome was the EORTC QLQ-CIPN20 total score evaluated longitudinally across the post-baseline treatment-period assessments before Cycles 3-6, with the score obtained before Cycle 2 included as the baseline covariate. The overall Group×Time interaction represented the primary treatment effect, and the baseline-adjusted between-group comparison before Cycle 6 represented the primary endpoint comparison. Secondary outcomes included the EORTC QLQ-CIPN20 sensory, motor, and autonomic domain scores; EORTC QLQ-C30 scale scores; DN4 total score and DN4-defined neuropathic pain positivity; and clinician-rated NCI-CTCAE v5.0 peripheral sensory neuropathy grade. A separate exploratory follow-up assessment was conducted 6 months after Cycle 6.

Conditions

CIPN - Chemotherapy-Induced Peripheral Neuropathy; Gastrointestinal Cancers

Keywords

Chemotherapy ınduced peripheral neuropathy; Nursing; compression; Oxaliplatin; Transcutaneous electrical nerve stimulation; Randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Baseline-Adjusted EORTC QLQ-CIPN20 Total Score Trajectory Across T1-T4

  The EORTC QLQ-CIPN20 is a 20-item patient-reported questionnaire assessing sensory, motor, and autonomic symptoms associated with chemotherapy-induced peripheral neuropathy. Scores are linearly transformed to a 0-100 scale, with higher scores indicating greater CIPN-related symptom burden. The primary outcome was the baseline-adjusted post-baseline trajectory of the EORTC QLQ-CIPN20 total score across T1-T4. The assessments before Cycles 3-6 (T1-T4) were modelled jointly, with the score obtained before Cycle 2 (T0) included as the baseline covariate. The overall Group-by-Time interaction constituted the primary treatment-effect test. Baseline-adjusted between-group contrasts at T4 constituted the primary endpoint pairwise comparisons.

  Before Cycles 3, 4, 5, and 6 (T1-T4), corresponding to 2, 4, 6, and 8 weeks after the T0 assessment before Cycle 2; each chemotherapy cycle lasted 14 days.

Secondary Outcomes (3)

• Baseline-Adjusted EORTC QLQ-C30 Scale Score Trajectories Across T1-T4

  Before Cycles 3, 4, 5, and 6 (T1-T4), corresponding to 2, 4, 6, and 8 weeks after the T0 assessment before Cycle 2; each chemotherapy cycle lasted 14 days.

• NCI-CTCAE v5.0 Peripheral Sensory Neuropathy Grade Across T1-T4

  Before Cycles 3, 4, 5, and 6 (T1-T4), corresponding to 2, 4, 6, and 8 weeks after the T0 assessment before Cycle 2; each chemotherapy cycle lasted 14 days.

• DN4 Total Score Trajectory and DN4-Defined Neuropathic Pain Positivity Across T1-T4

  Before Cycles 3, 4, 5, and 6 (T1-T4), corresponding to 2, 4, 6, and 8 weeks after the T0 assessment before Cycle 2; each chemotherapy cycle lasted 14 days.

Other Outcomes (4)

• Exploratory QLQ-CIPN20 Total Scores at 6-Month Follow-up

  At 6 months after completion of Cycle 6 (T5 exploratory follow-up assessment); each chemotherapy cycle lasted 14 days.

• Exploratory EORTC QLQ-C30 Scale Scores at 6-Month Follow-up

  At 6 months after completion of Cycle 6 (T5 exploratory follow-up assessment); each chemotherapy cycle lasted 14 days.

• Exploratory NCI-CTCAE v5.0 Peripheral Sensory Neuropathy Grade at 6-Month Follow-up

  At 6 months after completion of Cycle 6 (T5 exploratory follow-up assessment); each chemotherapy cycle lasted 14 days.

Study Arms (4)

TENS Group

EXPERIMENTAL

Participants received the TENS intervention at each scheduled session from Cycle 2 through Cycle 6 during oxaliplatin-based chemotherapy, in addition to usual care.

Device: TENS

Compression group

EXPERIMENTAL

Participants received the compression intervention at each scheduled session from Cycle 2 through Cycle 6 during oxaliplatin-based chemotherapy, in addition to usual care.

Device: Compression Garments

Sequential TENS Plus Compression Group

EXPERIMENTAL

Participants received TENS followed by compression at each scheduled intervention session from Cycle 2 through Cycle 6 during oxaliplatin-based chemotherapy, in addition to usual care.

Device: Sequential TENS Plus Compression

Usual Care Control Group

NO INTERVENTION

Participants received usual care from Cycle 2 through Cycle 6 and received no study-specific TENS or compression intervention.

Interventions

TENS DEVICE

TENS was delivered using the F. Bosch FB2405 TENS+EMS dual-channel device with four 5 × 5-cm surface electrodes placed bilaterally over PC6 and KI1. Program 4 provided a modulated pulse rate of 2-60 Hz and a pulse width of 156-260 microseconds. The device output was adjustable from 0-80 mA per channel into a 500-Ω load, but no fixed mA value was used. Intensity was individually titrated to a strong, comfortable, non-painful sensory level without visible muscle contraction. Each session lasted 180 minutes: 30 minutes before, throughout the 120-minute oxaliplatin infusion, and 30 minutes after the infusion. Sessions were administered every 14 days from Cycle 2 through Cycle 6, for five sessions.

TENS Group

Compression Garments DEVICE

Bilateral compression of the hands and feet was applied using Beybi Sensitive surgical gloves one size smaller than the participant's measured glove size and knee-high Varimed CCL II graduated compression stockings providing 23-32 mmHg. Each session lasted 180 minutes: 30 minutes before, throughout the 120-minute oxaliplatin infusion, and 30 minutes after the infusion. Sessions were administered every 14 days from Cycle 2 through Cycle 6, for five sessions. All applications were individually fitted and directly supervised by the same research nurse.

Compression group

Sequential TENS Plus Compression DEVICE

Participants received 90 minutes of TENS followed immediately by 90 minutes of bilateral hand-and-foot compression, using the same devices, parameters, electrode placement, gloves, and stockings as in the monotherapy groups. TENS began 30 minutes before the oxaliplatin infusion and continued during the first 60 minutes of the 120-minute infusion. After TENS was stopped and the electrodes were removed, compression was applied during the remaining 60 minutes of the infusion and for 30 minutes afterward. The total sequential intervention lasted 180 minutes. Sessions were administered every 14 days from Cycle 2 through Cycle 6, for five sessions.

Sequential TENS Plus Compression Group

Eligibility Criteria

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

You may qualify if:

• Aged 18 years or older
• Diagnosed with metastatic gastrointestinal cancer, including gastric, pancreatic, colon, or rectal cancer
• Scheduled to receive six cycles of oxaliplatin-based chemotherapy with FOLFOX or FOLFIRINOX
• Having received one cycle of oxaliplatin-based chemotherapy
• Having Grade 2 or higher chemotherapy-induced peripheral neuropathy according to NCI-CTCAE v5.0 before the Cycle 2 intervention
• Eastern Cooperative Oncology Group performance status of 0-2
• Having provided written informed consent to participate

You may not qualify if:

• Having a diagnosed psychiatric disorder that could interfere with informed consent, communication, or adherence to the study procedures
• Having a cardiac pacemaker or another implanted electronic device contraindicating TENS
• Having pre-existing peripheral neuropathy before the initiation of oxaliplatin-based chemotherapy or neuropathy attributable to another cause
• Having diabetes mellitus
• Having peripheral vascular disease or another clinically significant circulatory disorder affecting the hands or feet
• Having a skin lesion or other skin condition at the sites where TENS electrodes or compression garments would be applied

Sponsors & Collaborators

• Cumhuriyet University: lead

Study Sites (1)

Sivas Cumhuriyet University Health Services Application and Research Hospital

Sivas, Sivas, 58010, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Interventions

Transcutaneous Electric Nerve Stimulation

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Physical Therapy Modalities; Rehabilitation; Analgesia; Anesthesia and Analgesia

Study Officials

• Şerife KARAGÖZOĞLU, Proff.

  Cumhuriyet University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Because of the physical nature of the interventions, participants and intervention providers could not be blinded; therefore, the study was open-label. Group allocation was concealed from the enrolling researcher until assignment by the independent nurse. Coded group identities were concealed from the independent statistician until the statistical analyses were completed.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Participants were randomized in a 1:1:1:1 ratio to four parallel groups: usual care, compression, TENS, and sequential TENS followed by compression. Randomization was stratified by prespecified age categories (\<65 and \>=65 years) and sex. Within each stratum, a computer-generated fixed-block randomization sequence with a fixed block size of four was used. Each block contained one allocation to each of the four study groups, and the order of allocations was randomly permuted within each block. The allocation sequence was prepared and maintained by an independent oncology nurse. Participants remained in their originally assigned groups throughout the study.

Study Record Dates

• First Submitted: January 31, 2026
• First Posted: February 13, 2026
• Study Start: August 2, 2024
• Primary Completion: July 28, 2025
• Study Completion: January 28, 2026
• Last Updated: September 9, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)