TENS, Compression, and Cryotherapy for Paclitaxel-Induced Peripheral Neuropathy in Women With Breast Cancer

NCT07817979 | Completed

• 1 other identifier: CumhuriyetU-SBE-SÖ-2
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

This single-center, four-arm, parallel-group randomized controlled trial evaluates transcutaneous electrical nerve stimulation (TENS), compression, and cryotherapy for the management of chemotherapy-induced peripheral neuropathy (CIPN) in women with breast cancer receiving weekly adjuvant paclitaxel. A total of 140 participants with NCI-CTCAE Version 5.0 Grade 2 peripheral sensory neuropathy before the third weekly paclitaxel infusion were randomized in a 1:1:1:1 ratio to TENS, compression, cryotherapy, or routine care. The interventions were administered during weekly paclitaxel sessions from weeks 3 through 12. Outcomes were assessed at baseline before the third weekly infusion and before the sixth, ninth, and twelfth weekly infusions. The primary outcome is the EORTC QLQ-CIPN20 total score during the treatment period.

Conditions

Breast Cancer; Chemotherapy-Induced Peripheral Neuropathy

Keywords

nursing; breast cancer; electrostimülation; compression therapy; cryotherapy

Outcome Measures

Primary Outcomes (1)

• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 Total Score

  The EORTC QLQ-CIPN20 is a patient-reported questionnaire assessing chemotherapy-induced peripheral neuropathy symptoms experienced during the previous week. Item responses are used to calculate a total score that is linearly transformed to a 0-to-100 scale. Higher scores indicate greater peripheral neuropathy symptom burden. Follow-up scores at T1, T2, and T3 are evaluated jointly in a baseline-adjusted longitudinal model, with the T0 score included as the baseline covariate.

  Baseline before the third weekly paclitaxel infusion and first study intervention, and before the sixth, ninth, and twelfth weekly infusions, approximately 3, 6, and 9 weeks after baseline

Secondary Outcomes (3)

• Douleur Neuropathique 4 Questions (DN4) Total Score

  Baseline before the third weekly paclitaxel infusion and first study intervention, and before the sixth, ninth, and twelfth weekly infusions, approximately 3, 6, and 9 weeks after baseline

• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Global Health Status/Quality of Life Score

  Baseline before the third weekly paclitaxel infusion and first study intervention, and before the sixth, ninth, and twelfth weekly infusions, approximately 3, 6, and 9 weeks after baseline

• Peripheral Sensory Neuropathy Grade Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0

  Baseline before the third weekly paclitaxel infusion and first study intervention, and before the sixth, ninth, and twelfth weekly infusions, approximately 3, 6, and 9 weeks after baseline

Other Outcomes (3)

• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 Sensory Subscale Score

  Baseline before the third weekly paclitaxel infusion and first study intervention, and before the sixth, ninth, and twelfth weekly infusions, approximately 3, 6, and 9 weeks after baseline

• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 Motor Subscale Score

  Baseline before the third weekly paclitaxel infusion and first study intervention, and before the sixth, ninth, and twelfth weekly infusions, approximately 3, 6, and 9 weeks after baseline

• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 Autonomic Subscale Score

  Baseline before the third weekly paclitaxel infusion and first study intervention, and before the sixth, ninth, and twelfth weekly infusions, approximately 3, 6, and 9 weeks after baseline

Study Arms (4)

Transcutaneous Electrical Nerve Stimulation (TENS)

EXPERIMENTAL

Participants randomized to this arm received transcutaneous electrical nerve stimulation (TENS) once weekly during weekly paclitaxel sessions from week 3 through week 12, for a total of 10 planned sessions. TENS was delivered using a dual-channel, battery-powered portable digital Bosch TENS device and four self-adhesive hypoallergenic surface electrodes (5 × 5 cm or 5 × 9 cm, as appropriate). Electrodes were placed bilaterally over the PC6 region on the inner wrists and on the soles of the feet. Conventional high-frequency TENS was administered at 80 Hz with a pulse duration of 200-250 microseconds. Intensity was increased to produce a strong but comfortable tingling sensation without pain or visible muscle contraction, typically 10-30 mA and up to 60 mA according to tolerance. Each session lasted 120 minutes: 30 minutes before, 60 minutes during, and 30 minutes after the paclitaxel infusion.

Device: Transcutaneous Electrical Nerve Stimulation

Compression Therapy

EXPERIMENTAL

Participants randomized to this arm received compression therapy once weekly during weekly paclitaxel sessions from week 3 through week 12, for a total of 10 planned sessions. For the lower extremities, bilateral Varimed CCL II knee-high graduated compression stockings were selected according to ankle and calf measurements. The stockings provided 23-32 mmHg pressure at the ankle, with pressure decreasing gradually toward the calf. For the upper extremities, each participant's standard glove size was determined by hand measurement, and two layers of Beybi Gloves surgical gloves one size smaller were applied bilaterally. Hand pressure was not measured directly; the application was standardized using the same sizing procedure and double-glove technique. Each session lasted 120 minutes: 30 minutes before, 60 minutes during, and 30 minutes after the paclitaxel infusion.

Other: Compression Therapy

Cryotherapy

EXPERIMENTAL

Participants randomized to this arm received bilateral local cryotherapy once weekly during weekly paclitaxel sessions from week 3 through week 12, for a total of 10 planned sessions. Cryotherapy was applied to both hands and feet using glycerin-containing DETAMED Coolcare Chemotherapy Neuropathy Set cooling gel gloves and socks that completely covered the distal extremities and remained flexible when frozen. The gel gloves and socks were stored for at least 3 hours before each application in a freezer maintained at -20°C to -30°C. Cotton liners were worn under the gloves and socks, and the cooling sets were replaced at standardized intervals. Each session lasted 120 minutes: 30 minutes before, 60 minutes during, and 30 minutes after the paclitaxel infusion. Skin condition, peripheral circulation, and participant tolerance were monitored throughout each session.Cotton liners were worn under the gloves and socks, and the cooling sets were replaced every 30 minutes to maintain the cooli

Other: Cryotherapy

Routine Care Control

NO INTERVENTION

Participants randomized to this arm received routine oncological care and monitoring throughout the study and did not receive TENS, compression therapy, or cryotherapy. Routine care included clinical assessment before each weekly paclitaxel infusion, monitoring of treatment-related toxicities, standard patient education on recognizing and reporting chemotherapy-induced peripheral neuropathy symptoms, and pharmacological or supportive treatment prescribed by the responsible medical oncologist when clinically indicated. Routine nursing and medical care was provided by the same chemotherapy unit team regardless of randomized group. EORTC QLQ-CIPN20, DN4, NCI-CTCAE Version 5.0, and EORTC QLQ-C30 assessments were performed at the same time points as in the intervention arms: before the third, sixth, ninth, and twelfth weekly paclitaxel infusions.

Interventions

Transcutaneous Electrical Nerve Stimulation DEVICE

Conventional high-frequency transcutaneous electrical nerve stimulation (TENS) was administered once weekly from the third through the twelfth weekly paclitaxel infusion, for a total of 10 planned sessions. TENS was delivered using a dual-channel, battery-powered portable digital Bosch TENS device and four self-adhesive hypoallergenic surface electrodes. Electrodes were placed bilaterally over the PC6 region on the inner wrists and on the soles of the feet. The device was set to a frequency of 80 Hz and a pulse duration of 200-250 microseconds. Current intensity was increased gradually to produce a strong but comfortable tingling sensation without pain or visible muscle contraction, typically 10-30 mA and up to 60 mA according to participant tolerance. Each session lasted 120 minutes: 30 minutes before, 60 minutes during, and 30 minutes after the paclitaxel infusion.

Transcutaneous Electrical Nerve Stimulation (TENS)

Cryotherapy OTHER

Bilateral local cryotherapy was administered once weekly from the third through the twelfth weekly paclitaxel infusion, for a total of 10 planned sessions. Cryotherapy was applied to both hands and feet using glycerin-containing DETAMED Coolcare Chemotherapy Neuropathy Set cooling gel gloves and socks that completely covered the distal extremities and remained flexible when frozen. The gel gloves and socks were stored for at least 3 hours before each application in a freezer maintained at -20°C to -30°C. Cotton liners were worn under the gloves and socks, and the cooling sets were replaced at standardized intervals. Each session lasted 120 minutes: 30 minutes before, 60 minutes during, and 30 minutes after the paclitaxel infusion. Skin condition, peripheral circulation, and participant tolerance were monitored throughout each session.

Cryotherapy

Compression Therapy OTHER

Compression therapy was administered once weekly from the third through the twelfth weekly paclitaxel infusion, for a total of 10 planned sessions. For the lower extremities, bilateral Varimed CCL II knee-high graduated compression stockings were selected according to each participant's ankle and calf measurements. The stockings provided 23-32 mmHg pressure at the ankle, with pressure decreasing gradually toward the calf. For the upper extremities, each participant's standard glove size was determined by hand measurement, and two layers of Beybi Gloves surgical gloves one size smaller were applied bilaterally. Hand pressure was not measured directly; application was standardized using the same sizing procedure and double-glove technique. Each session lasted 120 minutes: 30 minutes before, 60 minutes during, and 30 minutes after the paclitaxel infusion. Fit, skin condition, peripheral circulation, and participant tolerance were monitored throughout each session.

Compression Therapy

Eligibility Criteria

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

You may qualify if:

• Female and 18 years of age or older.
• Diagnosed with early-stage or locally advanced breast cancer.
• Receiving 12 weeks of weekly paclitaxel as adjuvant treatment.
• Clinically confirmed National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0 Grade 2 peripheral sensory neuropathy during the third week of paclitaxel treatment, before the third weekly infusion and randomization.
• Eastern Cooperative Oncology Group performance status of 0-2 and Karnofsky Performance Status greater than 70.
• Able to communicate and complete the study procedures.
• Provided written informed consent to participate.

You may not qualify if:

• Peripheral neuropathy present before initiation of paclitaxel treatment.
• Diabetic neuropathy or another neurological disorder that could affect the assessment of peripheral neuropathy.
• Receiving paclitaxel as neoadjuvant, metastatic, or palliative treatment.
• Cardiac pacemaker or another implanted electronic device contraindicating transcutaneous electrical nerve stimulation.
• Active infection, open wound, serious skin lesion, or clinically significant peripheral circulatory impairment in the upper or lower extremities where the interventions would be applied.
• Raynaud phenomenon, cryoglobulinemia, cold urticaria, or another clinical condition contraindicating cryotherapy.
• Regularly receiving another physical intervention for chemotherapy-induced peripheral neuropathy outside the study at enrollment or planning to receive such an intervention during the study.

Sponsors & Collaborators

• Cumhuriyet University: lead

Study Sites (1)

CumhuriyetU

Merkez, Sivas, 58010, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Transcutaneous Electric Nerve Stimulation; Cryotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Participants, the intervention provider, the outcome assessor, and the analyst were not masked to group assignments. Because TENS, compression, and cryotherapy were visible and physically perceptible, masking of participants and the intervention provider was not feasible. Patient-reported outcomes were completed by participants who were aware of their assigned groups. NCI-CTCAE peripheral sensory neuropathy grading and the clinical examination components of the DN4 were performed before the weekly paclitaxel infusion and study intervention using standardized assessment procedures. Therefore, the study was conducted as an open-label trial.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Oncology Nurse

Model Details: Participants were randomized in a 1:1:1:1 ratio to four parallel groups: transcutaneous electrical nerve stimulation, compression, cryotherapy, or routine care.

Study Record Dates

• First Submitted: August 6, 2026
• First Posted: September 14, 2026
• Study Start: April 27, 2025
• Primary Completion: August 15, 2026
• Study Completion: August 15, 2026
• Last Updated: September 14, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)