Comparative Effects of Transcutaneous Electrical Nerve Stimulation, Compression, and Sequential TENS Plus Compression on Established Oxaliplatin-Induced Peripheral Neuropathy in Patients With Metastatic Gastrointestinal Cancer: A Four-Arm Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 140
- 试验地点
- 2
- 主要终点
- Change in EORTC QLQ-CIPN20 Total Score From Before Cycle 2 to Before Cycle 6
研究概览
简要总结
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.
详细描述
This randomized, open-label, four-arm parallel-group study evaluated supportive interventions for the management of established chemotherapy-induced peripheral neuropathy in patients receiving oxaliplatin-based chemotherapy. Eligible participants were adults with metastatic gastrointestinal cancer who had received one cycle of FOLFOX or FOLFIRINOX and had Grade 2 or higher peripheral sensory neuropathy according to NCI-CTCAE v5.0 before the Cycle 2 intervention.
A total of 140 participants were randomly allocated in a 1:1:1:1 ratio to TENS, compression, sequential TENS followed by compression, or usual care, with 35 participants in each group. Participants remained in their assigned parallel groups throughout the study. Intervention sessions were administered at 14-day intervals from Cycle 2 through Cycle 6, resulting in five sessions per participant.
The prespecified peri-infusion intervention window lasted 180 minutes, comprising 30 minutes before, 120 minutes during, and 30 minutes after the oxaliplatin infusion. In the TENS group, transcutaneous electrical nerve stimulation was administered throughout this 180-minute window. TENS was delivered using Program 4 of the F. Bosch FB2405 TENS+EMS device. Program 4 provided frequency- and pulse-width-modulated stimulation, with pulse rates ranging from 2 to 60 Hz and pulse widths ranging from 156 to 260 microseconds. The 40-Hz value informed the original intervention rationale; however, the actual stimulation was not a fixed 40-Hz, 100-microsecond output. Intensity was individually titrated to produce a strong but comfortable and non-painful sensory sensation without visible muscle contraction.
In the compression group, bilateral compression of the hands and feet was applied throughout the same 180-minute peri-infusion window. Surgical gloves one size smaller than each participant's individually determined size and Class II graduated compression stockings providing 23-32 mmHg were used.
Because no established combined TENS-plus-compression dosing protocol was available, participants in the sequential intervention group received 90 minutes of TENS followed by 90 minutes of compression within the same 180-minute peri-infusion window. TENS began 30 minutes before the oxaliplatin infusion and continued during the first 60 minutes of the 120-minute infusion. After TENS was discontinued and the electrodes were removed, compression was initiated and maintained during the remaining 60 minutes of the infusion and for 30 minutes after its completion. The usual-care control group received routine clinical care without a study-specific TENS or compression intervention.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None (Participant)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
This study is a four-group study. The severity of neuropathy will be compared in Compression
Compression
干预措施: compression (Other)
This study is a four-group study. The efficacy and severity of neuropathy will be compared in TENS,
TENS
干预措施: TENS (Device)
This study is a four-group study. The efficacy and severity of neuropathy will be compared in TENS,
TENS
干预措施: compression (Other)
This study is a four-group study. The efficacy and severity of neuropathy will be compared in TENS,
TENS
干预措施: TENS+Compression interventions (Device)
This study is a four-group study. The severity of neuropathy will be compared in Compression
Compression
干预措施: TENS+Compression interventions (Device)
This study is a four-group study. The severity of neuropathy will be compared in Compression
Compression
干预措施: TENS (Device)
This study is a four-group study. The severity of neuropathy will be compared in TENS+Compression
TENS+Compresion
干预措施: TENS (Device)
This study is a four-group study. The severity of neuropathy will be compared in TENS+Compression
TENS+Compresion
干预措施: compression (Other)
This study is a four-group study. The severity of neuropathy will be compared in TENS+Compression
TENS+Compresion
干预措施: TENS+Compression interventions (Device)
This study is a four-group study. The severity of neuropathy will be compared in Control
Control group
干预措施: TENS+Compression interventions (Device)
This study is a four-group study. The severity of neuropathy will be compared in Control
Control group
干预措施: TENS (Device)
This study is a four-group study. The severity of neuropathy will be compared in Control
Control group
干预措施: compression (Other)
TENS Group
Participants received the TENS intervention at each scheduled session from Cycle 2 through Cycle 6 during oxaliplatin-based chemotherapy, in addition to usual care.
干预措施: TENS (Device)
Usual Care Control Group
Participants received usual care from Cycle 2 through Cycle 6 and received no study-specific TENS or compression intervention.
Sequential TENS Plus Compression Group
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.
干预措施: Sequential TENS Plus Compression (Device)
Compression group
Participants received the compression intervention at each scheduled session from Cycle 2 through Cycle 6 during oxaliplatin-based chemotherapy, in addition to usual care.
干预措施: Compression Garments (Device)
结局指标
主要结局
Change in EORTC QLQ-CIPN20 Total Score From Before Cycle 2 to Before Cycle 6
时间窗: From baseline before Cycle 2 to before Cycle 6, with assessments every 14 days (five assessments over approximately 8 weeks [56 days]).
The EORTC QLQ-CIPN20 is a 20-item patient-reported questionnaire assessing sensory, motor, and autonomic symptoms and functional limitations associated with chemotherapy-induced peripheral neuropathy. Scores were linearly transformed to a 0-100 scale, with higher scores indicating greater CIPN-related symptom burden. The primary outcome was the between-group difference in change in the total score from baseline before Cycle 2 to Cycle 6.
Baseline-Adjusted EORTC QLQ-CIPN20 Total Score Trajectory Across T1-T4
时间窗: 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.
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.
EORTC QLQ-C30 Quality of Life Scale
时间窗: 10 weeks
EORTC QLQ-C30 Version 3.0 (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3.0) is a widely used scale for evaluating the quality of life of cancer patients, developed by Aaronson et al. (2017). The Cronbach's alpha coefficient of the scale was determined to be ≥ 0.70. EORTC QLQ-C30 consists of 3 sub-dimensions and a total of 30 questions.
次要结局
- Change in EORTC QLQ-C30 Scale Scores From Before Cycle 2 to Before Cycle 6(From baseline before Cycle 2 to before Cycle 6, with assessments every 14 days (five assessments over approximately 8 weeks [56 days]).)
- NCI-CTCAE v5.0 Peripheral Sensory Neuropathy Grade From Before Cycle 2 to Before Cycle 6(From baseline before Cycle 2 to before Cycle 6, with assessments every 14 days (five assessments over approximately 8 weeks [56 days]).)
- Change in DN4 Total Score From Before Cycle 2 to Before Cycle 6(From baseline before Cycle 2 to before Cycle 6, with assessments every 14 days (five assessments over approximately 8 weeks [56 days]).)
- 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.)
- EORTC QLQ-CIPN20(10 weeks)
研究者
Sevcan Özkan
Principal Investigator
Cumhuriyet University