Clinical trial NCT03626220: Acupuncture on Chemotherapy-induced Peripheral Neuropathy
Official title: Evaluation the Efficacy of Acupuncture in Chemotherapy Induced Peripheral Neuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Randomized Controlled Trial
Breast Cancer
Chemotherapy-induced Peripheral Neuropathy
Acupuncture
Keywords: acupuncture
chemotherapy-induced peripheral neuropathy
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
First posted: 2018-08-10
Enrollment: 20
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1. The acupuncture group: Acupuncture treatment will be performed for 9 weeks. The frequency of acupuncture will be twice a week for the first six weeks, and once a week for the following three weeks. 30 minutes needling at each treatment. Acupuncture points include Baihui(GV20), Qihai(CV6), Quchi(LI11), Hegu(LI4), Neiguan(P6), or Shenmen(HT7) for upper limbs. For plantar numbness, choose two acupoints to use in turn; use Weizhong(BL40), Sanyinjiao(SP6), or Zusanli(ST36) for lower limbs. If severe numbness occurred, Taixi(KI3) or Yongquan(K1) should be added for feet numbness. "De qi" sensation, such as soreness, numbness, pain, etc. will be achieved at each acupoints .
2. The Controlled group: Acupuncture with superficial needling 0.5 cun (estimated 1cm with deviation depends on the body size of each participants) away from the acupoints, which only superficially penetrated the skin without feeling of "De Qi" sensation.
Primary purpose: TREATMENT

Brief summary: Peripheral neuropathy is currently the second most common side effect after chemotherapy, second only to the side effects of blood toxicity. A variety of chemotherapy drugs may induce peripheral neurotoxicity and cause by the cumulative dose of chemotherapy drugs. Symptoms include sensory paresthesia, feeling dullness or numbness, glove-like feeling distributed in the palm. The currently most effective way is to interrupt the treatment or adjust the dose of chemotherapeutic drugs, but it is easy to make patients discontinue chemotherapy. The purpose of this study is to explore the impact of acupuncture on neurological symptoms and quality of life. Three kinds of questionnaires will be used:(1) Brief pain inventory- short form to assess the extent of pain, and the impact of daily life. (2) the Functional Assessment of Cancer Therapy/ Gynecologic Oncology Group- Neurotoxicity(FACT/GOG-NTX)-13 (Version 4) to assess changes in neurological symptoms; (3) World Health Organization Quality of Life Scale-(WHOQOL-BREF) to assess changes in the quality of life of patients. The course of treatment was evaluated for nine weeks. Changes in neurological function and quality of life will be evaluated before treatment, the third week of treatment, the sixth week of treatment, till the ninth week. The aim of this study is to confirm that acupuncture can improve peripheral neuropathy after chemotherapy, in order to enhance breast cancer patients' quality of life, and provide the new opportunity for integrative therapy between Chinese and Western medicine.

Keywords：acupuncture , chemotherapy-induced peripheral neuropathy

Detailed description: (I) Background of the research A variety of neurotoxic chemotherapeutic agents, including platinums (e.g. cisplatin, carboplatin, and oxaliplatin), taxanes (e.g. paclitaxel and docetaxel), and vinca alkaloids (e.g. vincristine and vinblastine), thalidomide and bortezomib, may induce peripheral neuropathy. Generally speaking, sensory nerve dysfunction is more common than motor involvement. It causes hands and feet to feel tingling, dullness or numbness symmetrically, which will be a glove-like ("glove-and-stocking type") sensation distributed in palms and soles. Patient's touch, vibration, and proprioception senses may be impaired under clinical examinations.

chemotherapy-induced peripheral neuropathy(CIPN) relates to the cumulative doses of chemotherapeutic agents. Sometimes, when chemotherapy is stopped, neuropathy symptoms may continue or worsen, which is called a "costing phenomenon". Nerve damaging usually starts from ends of the extremities, while individual doses were accumulated, it gradually extends to proximal joints or ganglions. CIPN is currently the second most common side, next to hematotoxicity. Within thirty days after chemotherapy, 68.1% of patients may develop CIPN, most of which can be relieved or improved, but there are still 30-83% symptoms persist over 6 months.

At present, the most effective way to treat CIPN is to stop the treatment protocol or adjust doses of chemotherapy; however, it affects the effect of chemotherapy in degrading tumor growth. Plenty of pharmacological or non-pharmacological treatments are still under investigation, such as antioxidant medication (e.g. Acetyl-L-carnitine, glutamine, vit B12, fish oil, etc.), anxiolytics (e.g. venlafaxine), neuroprotective agents (e.g. infusion of calcium ions, magnesium ions), food supplements, acupuncture, light stimulation, etc. Acupuncture with the advantages of clinically effective, easy-practice and relatively safe, few studies revealed its effect on CIPN, however, there is still a lack of large clinical trials to evaluate its effectiveness.

(ii) Purpose of the research To investigate the efficacy of acupuncture on peripheral neuropathy after chemotherapy administration in patients with breast cancer.

(iii) Importance of the research Current studies revealed that acupuncture might be effective on CIPN, however, insufficient number of participants or lack of control groups limit the quality of clinical studies. Therefore, the aim of our study to conduct a randomized controlled clinical trial to evaluate the efficacy of acupuncture on peripheral neuropathy caused by chemotherapy.

Eligibility criteria: The inclusion criteria will be: female more than 20 years of age; breast cancer with early stage at I-III; had completed chemotherapy; the neurotoxic chemotherapeutic agents included taxanes, platinums, or others; less than grade three in the Eastern Cooperative Oncology Group (ECOG) status; higher than grade one in National Cancer Institute-common terminology criteria for adverse events(NCI-CTCAE) scale.

The exclusion criteria will be: having less than three months in mean survival time, history of diabetic neuropathy before chemotherapy administration, history of other preexisting peripheral neuropathy, other inflammatory or metabolic arthritis, severe blood coagulation diseases or with latent bleeding tendency, unstable cardiovascular diseases, or other preexisting muscle-skeletal diseases.

Primary outcomes:
measure: The Average Pain Severity in the Brief Pain Inventory-Short Form(BPI-SF)
timeFrame: We measured the average pain severity 4 times within 9 weeks [at baseline (before the first treatment) and week 3, week 6, and week 9 during the protocol].
Secondary outcomes:
measure: Functional Assessment of Cancer Therapy/ Gynecologic Oncology Group- Neurotoxicity(FACT/GOG-NTX)-13
timeFrame: 4 times within 9 weeks: at baseline (before the first treatment) and week 3, week 6, and week 9 during the protocol
measure: World Health Organization Quality of Life Scale(WHOQOL)-BREF (Taiwan Version)
timeFrame: We measured 2 times within 9 weeks: before and after treatment
measure: Touch Test Sensory Evaluator
timeFrame: 2 times within 9 weeks: before and after treatment
Other outcomes:
measure: Explore the Neuroprotective Mechanism of Acupuncture
timeFrame: 2 times within 9 weeks: before and after treatment
Locations:
city: Tainan
country: Taiwan
facility: An Nan Hospital, China Medical University
Study officials:
affiliation: An Nan Hospital, China Medical University, Tainan, Taiwan, R.O.C.
name: Chien-Chen Huang, M.S.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Franconi G, Manni L, Schroder S, Marchetti P, Robinson N. A systematic review of experimental and clinical acupuncture in chemotherapy-induced peripheral neuropathy. Evid Based Complement Alternat Med. 2013;2013:516916. doi: 10.1155/2013/516916. Epub 2013 Jul 24.
citation: Park SB, Goldstein D, Krishnan AV, Lin CS, Friedlander ML, Cassidy J, Koltzenburg M, Kiernan MC. Chemotherapy-induced peripheral neurotoxicity: a critical analysis. CA Cancer J Clin. 2013 Nov-Dec;63(6):419-37. doi: 10.3322/caac.21204.
citation: Greenlee H, Crew KD, Capodice J, Awad D, Buono D, Shi Z, Jeffres A, Wyse S, Whitman W, Trivedi MS, Kalinsky K, Hershman DL. Randomized sham-controlled pilot trial of weekly electro-acupuncture for the prevention of taxane-induced peripheral neuropathy in women with early stage breast cancer. Breast Cancer Res Treat. 2016 Apr;156(3):453-464. doi: 10.1007/s10549-016-3759-2. Epub 2016 Mar 25.
citation: Wong R, Major P, Sagar S. Phase 2 Study of Acupuncture-Like Transcutaneous Nerve Stimulation for Chemotherapy-Induced Peripheral Neuropathy. Integr Cancer Ther. 2016 Jun;15(2):153-64. doi: 10.1177/1534735415627926. Epub 2016 Apr 29.