Electro-acupuncture for the Prevention and Treatment of Oxaliplatin-induced Neurotoxicity in Colorectal Cancer Patients

Study Overview
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Brief Summary
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In this study, a 24-week randomized, sham-controlled, single-blind, multicenter clinical trial will be conducted to explore the effect of electroacupuncture for prevention and treatment of both acute and chronic neurotoxicity through both clinical and biological indicators.

Detailed Description
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This is a prospective, randomized, sham-controlled, double-blinded and multiple center trial on electro-acupuncture for preventing and treating symptoms of chemotherapy-induced neurotoxicity in patients with colorectal cancer. A total of 150 candidates will be recruited in this study four weeks before chemotherapy for best preventive effect. They will be assigned randomly into either the electro-acupuncture or the sham-control group with 1:1 ratio. Both groups will receive a total of 24 sessions of interventions (4 weeks before chemotherapy and 8 weeks during chemotherapy, with 2 session per week), and will be followed up regularly for up to 12 weeks after completion of the acupuncture.

Official Title
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Electro-acupuncture for the Prevention and Treatment of Oxaliplatin-induced Neurotoxicity in Colorectal Cancer Patients: a Prospective, Randomized, Sham-controlled, Double-blinded and Multicenter Study

Conditions
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Oxaliplatin, Colorectal Cancer, Electro-acupuncture, Neurotoxicity

Intervention / Treatment
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* Device: Acupuncture
* Device: Sham-acupuncture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: are aged ≥18 years old; are newly diagnosed with stage II to IV colorectal cancer; going to receive adjuvant oxaliplatin-based chemotherapy within 4 weeks; had not received any acupuncture in the previous 3 months and had a life expectancy ≥ of six months. Exclusion Criteria: are not able to comprehend and communicate; are not able to read Chinese; have prior peripheral neuropathy caused by other diseases including diabetes, stroke, cardiovascular diseases such as arrhythmia, heart failure, myocardial infarction, and patients with cardiac pacemakers; have a bleeding tendency; are pregnant or breastfeeding; have impaired hepatic or renal function; using any pharmaceutical agents e.g., vitamin B6 and vitamin E, or herbal medication. All the above medication prescribed by physicians or Chinese medicine practitioners during the study will be recorded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Electro-acupuncture group<br>The electro-acupuncture intervention will be conducted for 2 sessions per week for 4 consecutive weeks before and 8 weeks during the chemotherapy. In this study eight acupoints are chosen: he gu (LI4), nei guan (PC6), qu chi (LI12), ba xie (EX-UE9), zu san li (ST36), san yin jiao (SP6), tai chung (LV3) and ba feng (EX-LE10). The use of ba xie (EX-UE9) and ba feng (EX-LE10) will be optional if skin lesions of hands and feet occur due to Capecitabine (Xeloda). Disposable acupuncture needles (verum acupuncture needles Hwato 0.25 x 25mm matching the Streiterger sham needles) will be inserted at a depth of 10-25mm into the points. Electrical stimulation will be delivered with continuous waves at 2 Hz, at an intensity of each patient's minimum sensation of stimulation through the electrical acupuncture stimulation instrument. The needles will be retained in position for 25 minutes. | Device: Acupuncture<br>* Disposable acupuncture needles (0.25 mm in diameter and 25 mm in length) are straightly into body acupuncture points (he gu (LI4), nei guan (PC6), qu chi (LI12), ba xie (EX-UE9), zu san li (ST36), san yin jiao (SP6), tai chung (LV3) and ba feng (EX-LE10)). The use of ba xie (EX-UE9) and ba feng (EX-LE10) will be optional if skin lesions of hands and feet occur due to Capecitabine (Xeloda). Electrical stimulation will be delivered with continuous waves at 2 Hz, at an intensity of each patient's minimum sensation of stimulation through the electrical acupuncture stimulation instrument. The needles will be retained in position for 25 minutes.<br>|
| Sham Comparator: sham-acupuncture group<br>For subjects assigned to the sham control group, Streitberger's non-invasive acupuncture needles (Gauge 8 x 1.2/ 0.30 x 30mm) will be applied to serve as a sham control at the same acupoints with the same stimulation modality, and the stimulation will be a pseudo stimulation, which will be given by connecting the needle to the incorrect output socket of the electrical acupuncture stimulation instrument.The credibility and validity of this system have been well demonstrated. | Device: Sham-acupuncture<br>* Streitberger's non-invasive acupuncture needles (Gauge 8 x 1.2/ 0.30 x 30mm) will be applied to serve as a sham control at the same acupoints with the same stimulation modality and then connecting the needle to the incorrect output socket of the electrical acupuncture stimulation instrument. The sham points are pseudo stimulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score Changes on the FACT/GOG-Ntx questionnaire | The questionnaire includes 11 questions covering sensory neuropathy, motor neuropathy, hearing neuropathy, and dysfunction associated with neuropathy, which results in a cumulative score ranging from 0 to 44, with the lower scores reflecting worse neuropathy symptoms. | 0-24 weeks; weekly | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| numerical rating scale (NRS) | Patients will be asked to rate their average neuropathy symptoms within one week, on an 0 to 10 scale (0=no symptoms; 10=worst possible symptoms), those <4 of 10 NRS will be considered as mild neuropathy while ≥4 of 10 NRS will be considered as moderate to severe neuropathy. | 0-24 weeks; weekly | 
| European Organization for Research and Treatment of Cancer (EORCTC) quality of life questionnaire QLQ-C30 | A 30-items questionnaire assessing five functional scales (physical, role, cognitive, emotional and social), three symptoms scales (fatigue, pain, nausea and vomiting), and other symptoms and problem in cancer patients (dyspnoea, appetite loss, insomnia, constipation, diarrhoea, and financial difficulties). | 0,3,6,9,12,15,18,21,24 weeks | 
| Constitution of Chinese Medicine Questionnaire (CCMQ) | CCMQ has 60 items measuring the 9 body constitution types: gentleness, Qi-deficiency, Yang-deficiency, Yin-deficiency, phlegm-wetness, wetness-heat, blood-stasis, Qi-depression, and special diathesis. | 0,12,24 weeks | 
| Vibration sense test | It will be assessed using the graduated Rydel-Seiffer tuning fork (U.S. Neurologicals, Poulsbo, WA), with printed directions for use and its normative data. Readings will be averaged and recorded as the vibration value. | 0-12 week; weekly | 
| Light touch test | It will be assessed with standard 10g monofilaments, contained within the Neuropen (Owen Mumford, Woodstock, UK). During testing, the fiber will be applied perpendicular to the plantar surface of the great toe and the palmar surface of the index finger until the fiber begins to bend and will be held in place for 1 second and then removed. This procedure will be repeated 3 times and the patient will be asked to report the ability to feel the fibe. | 0-12 week; weekly | 
| Short Form 12 item(version 2) Health Survey (SF-12V2) | The SF-12V2 is a widely used generic HRQoL instrument, and its Chinese version has been validated and normed in the general Chinese population in Hong Kong. It consists of 12 questions measuring eight domains of health, including physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The scores are generated using an algorithm to generate a combined physical and mental health score for comparison with normative data. In the normative data: 1) the mean score was set to 50; 2) a score > 50 indicated better physical or mental health than the mean; 3) a score < 50 indicated worse physical or mental health than the mean. | 0-12 week; weekly |