Evaluating the Effects of Acupuncture in the Treatment of Taxane Induces Peripheral Neuropathy

Study Overview
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Brief Summary
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Taxane Induced Peripheral Neuropathy (TIPN) is a major dose limiting side effect of taxane chemotherapies and it often reduces the success of the patient treatment. Treating TIPN is difficult and at this time conventional treatment is primarily limited to the global use of antidepressants and anticonvulsants. Acupuncture treatment has been used for symptom improvement in patients with peripheral neuropathy caused by HIV and diabetes mellitus; however, few studies have evaluated acupuncture as a viable treatment for taxane induced peripheral neuropathy. This study will enroll female breast cancer survivors at the Greenville Health System Cancer Institute Center for Integrative Oncology and Survivorship to assess whether acupuncture holds any therapeutic benefit for TIPN and how it influences the mechanisms underlying resolution of TIPN. This would provide critical validation of acupuncture and increase potential for other forms of chemotherapy induced peripheral neuropathy.

Detailed Description
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Taxane induced peripheral neuropathy (TIPN) affects many female breast cancer survivors treated with taxane chemotherapies. This condition can include symptoms ranging from minor loss of sensory function, numbness and mild paresthesia to frank pain including burning or tingling sensation or shooting neuropathic pain. Treating TIPN is difficult and at this time conventional treatment is primarily limited to the use of antidepressants and anticonvulsants, both of which have significant efficacy and safety issues with often little reduction in TIPN. The mechanisms of taxane induced peripheral tissue damage are becoming clearer allowing for the potential to develop specific interventions to resolve pain associated with this class of drug. Acupuncture treatment has been used for symptom improvement in patients with peripheral neuropathy caused by HIV and diabetes mellitus; however, few studies have evaluated acupuncture as a viable treatment for taxane induced peripheral neuropathy. Moreover, there has been little research considering the biological effect of acupuncture treatment related to the mechanisms of pain resolution. This study will enroll female breast cancer survivors at the Greenville Health System Cancer Institute Center for Integrative Oncology and Survivorship undergo an acupuncture protocol consisting of traditional acupuncture points used for neuropathic pain. This is a prospective, randomized, controlled trial that will consist of two arms. The two arms will consist of 1) acupuncture plus conventional therapy and 2) conventional therapy only (n= 9 participants in each arm). Arm 1 will receive a traditional manual acupuncture protocol twice a week for 6 weeks and once a week for 6 weeks in conjunction with standard of care treatment. Arm 2 will receive standard of care treatment only; acupuncture will be offered to these individuals after a 12 week waitlist. The 18 participants will start an individualized 12 week study schedule and will be recruited over a 4 month time period. This study will assess severity of pain, inflammatory biomarkers, and circulating levels of mitochondrial DNA at baseline, 6 weeks, and 12 weeks for both arms through questionnaires and blood tests. Results of the study will further clarify acupuncture's role as a therapeutic modality for managing pain induced by TIPN while providing evidence that could help unlock a better understanding of its actions.

Official Title
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Evaluating the Effects of Acupuncture in the Treatment of Taxane Induces Peripheral Neuropathy (TIPN)

Conditions
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Peripheral Neuropathy

Intervention / Treatment
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* Other: Acupuncture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed primary invasive carcinoma of the breast (stage I, II, or III) Completed active chemotherapeutic with taxane therapy (taxotere, Taxol, Abraxane) within the last 24 months Established diagnosis of motor and sensory neuropathy greater or equal to 2 according to the CTCAE v 4.03 scale in spite of previous treatment with Neurontin, Cymbalta and/or Lyrica Read, understand, and speak English Exclusion Criteria: Currently undergoing active treatment with chemotherapy (not including TKI's or other targeted therapy) Any acupuncture treatment for any indication within the 30 days of enrollment Cardiac Pacemaker Deformities that interfere with accurate acupuncture point locations Local infection at or near the acupuncture site Pregnant or currently lactating Medical History of chronic alcohol use Mental incapacitation or significant emotional or psychological disorder

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>The nine participants in the intervention arm will receive 18 acupuncture treatments over the course of 12 weeks (2 treatments per week for 6 weeks and 1 treatment per week for 6 weeks). They will undergo assessments at baseline, 6 weeks, and 12 weeks through the use of questionnaires and blood tests. The participants will also be allowed to continue their conventional therapy for TIPN. | Other: Acupuncture<br>* Acupuncture uses tiny needles to promote blood flow, nervous system signaling, and brings the body back into homeostasis which the state of optimum functioning. Treatment for taxane induced peripheral neuropathy will consist of traditional acupuncture and will use points located in the foot (SP 3, ST 41, LR 3, K 3, GB 41), knee (SP 9, ST 36, K 10, GB 34), and arm (LI 11). Participants will continue to take their conventional therapy. Each acupuncture treatment will take place at Oriental Medicine Associates with trained acupuncturist, William Hendry. Each session should last about 30 minutes.<br>|
| No Intervention: Control<br>The nine participants in this arm will undergo the same assessments as the intervention arm at baseline, 6 weeks, and 12 weeks. They will not receive any acupuncture treatments during this time, but will be allowed to continue their conventional therapy. The control arm will be offered the same 18 acupuncture treatments after a wait of at least 12 weeks. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in taxane induced peripheral neuropathy symptoms measured by the Patients' Global Impression of Change (PGIC) scale. | All 18 participants will complete the PGIC scale at 6 weeks and 12 weeks. This scale will ask questions about the participants' change in activity limitations, symptoms, emotions, and overall quality of life related to their peripheral neuropathy since the beginning of treatment. | 12 Weeks | 
| Evaluate the mechanism of acupuncture as a treatment of TIPN through quantification of inflammatory biomarkers and circulation levels of mitochondrial DNA (mtDNA) | Approximately 8ml of blood will be collected from each participant at baseline, 6 weeks, and 12 weeks. The samples will be collected in purple top BD vacutainers. | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quality of life using the FACT/GOG-NTX questionnaire | Participants will complete the FACT/GOG-NTX questionnaire at baseline, 6 weeks, and 12 weeks. The questionnaire includes questions about the participants' physical, social/family, emotional, and functional well-being. | 12 Weeks | 
| Evaluate if neuropathic mechanisms are contributing to pain measured by the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale | Participants will complete the LANSS Pain Scale at baseline, 6 weeks, and 12 weeks. This pain scale involves a pain questionnaire and sensory testing to determine to determine if neuropathic mechanisms are still contributing to the participant's pain. | 12 Weeks | 
| Change in taxane induced peripheral neuropathy related pain measured by the Brief Pain Inventory (BPI). | Participants will complete the BPI at baseline, 6 week, and 12 week. The BPI will ask questions to detail how the pain interferes with the participants' general activity, mood, walking ability, relationships, sleep, and enjoyment of life. | 12 Weeks |