Auricular Point Acupressure to Manage Chemotherapy Induced Neuropathy

Study Overview
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Brief Summary
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The proposed randomized control trial will evaluate auricular point acupressure (APA) on chemotherapy-induced neuropathy (CIN), rigorously considering point specificity and placebo effects by integrating self-report measures, psychophysical measures (QST), endogenous biomarkers (cytokines), and neuro-imaging to investigate APA's efficacy and underlying mechanism(s). The investigators will use a randomized control trial, three-group design: (1) APA Group, (2) Sham APA Control, and (3) Usual Care Control. A smartphone application for ecological momentary assessment (EMA) will be used to monitor APA adherence and capture momentary CIN severity and analgesic use.

Detailed Description
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Chemotherapy-induced neuropathy (CIN)-pain, numbness, or tingling distributed in the hands and feet-produces persistent symptoms affecting sensation and balance in cancer survivors. Up to 50% of cancer survivors still suffer CIN 6 years after treatment. Duloxetine, the only recommended drug by the American Society of Clinical Oncology, was found to be superior to placebo but improved CIN by only 0.73 points (0-10 scale). No effective treatment for CIN has been established except exercise, with an effect size of <0.508. Opioids relieve CIN pain, but long-term use is strongly discouraged due to opioid overuse. The investigators propose to test auricular point acupressure (APA), an innovative and scalable solution developed from auricular acupuncture. APA is a non-invasive (needleless) and active treatment for patients with pain, whereas acupuncture is an invasive (using needles) and passive treatment (administered by a licensed practitioner). In APA, small seeds are taped on specific ear points by a skilled provider and patients press on the seeds to stimulate ear points three times daily, three minutes per time, for a total of nine minutes per day. APA provides pain relief within 1-2 minutes after ear stimulation and sustains pain relief for one month after a 4-week APA intervention. APA is popular in Taiwan, China, and Europe. Though its use is sparse in the U.S., a limited number of clinical trials have supported APA in pain management.

Official Title
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Auricular Point Acupressure to Manage Chemotherapy Induced Neuropathy

Conditions
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Chemotherapy-induced Neuropathy

Intervention / Treatment
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* Other: Virtual Auricular Point Acupressure (APA)
* Other: In-Person Training
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: cancer patients ages ≥18 years have received a medication in one of the following categories: platinum-based, vinca alkaloids, bortezomib, eribulin, and/or taxanes have completed their course of chemotherapy three months or more before enrollment have CIN due to receiving neurotoxic chemotherapy for cancer or have pre-existing peripheral neuropathy of another etiology that worsened after chemotherapy have one of the average intensity of pain, or numbness, or tingling on their extremities the previous week due to CIN ≥ 4 on a 11-point numerical scale. Exclusion Criteria: use of an investigational agent for pain control concurrently or within the past 30 days use of an implantable drug delivery system, e.g. Medtronic SynchroMed® prior celiac plexus block or other neurolytic pain control treatment other identified causes of painful paresthesia existing prior to chemotherapy (e.g., radiation or malignant plexopathy, lumbar or cervical radiculopathy,) allergy to latex (the tapes for the APA include latex).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: This prospective randomized controlled study will randomly assign participants into three groups: (1) APA Group (Self-Learn APA), (2) In-Person Group (In person training), and (3) Usual Care Control. During intervention phase, participants in the APA and In-Person groups will receive four in-person seed placement with weekly cycles, while Usual Care Group will receive counseling related how to self-manage their CIN to control time and attention. Participants in Usual Care will be re-randomized to APA or In-Person groups after completion of the study assessment. This proposed trial will evaluate the APA sustained effects for CIN up to a 3-month follow-up. The data will be collected at pre-intervention (T1), post-completion of the 4-week APA treatment (T2), and follow-ups at monthly post-completion of treatment for 3 months (T3-T5), for a total of 5 assessments. The primary endpoint is at 1-month follow-up.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APA Group<br>A self-guided smartphone application to self-administered APA | Other: Virtual Auricular Point Acupressure (APA)<br>* Participants will learn how to self-administer APA by themselves.<br>|
| Experimental: Virtual APA group<br>A virtual APA (vAPA): APA app+ plus secure zoom sessions for APA coaching with questions and answers | Other: In-Person Training<br>* Participants will receive in-person training to self-administer APA.<br>|
| Active Comparator: Usual Care Control<br>Wait-List Usual Care Control (UC) | Other: Usual Care<br>* Participants will continue to do whatever they are receiving from their oncologist.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain severity as assessed by the Brief Pain Inventory | Pain severity will be assessed using the revised Brief Pain Inventory (BPI). The scale ranges from 0 (no pain) to 10 (severe pain). | Up to 4 months | 
| Change in numbness as assessed by the Brief Pain Inventory | Numbness will be assessed using the revised Brief Pain Inventory (BPI). The scale ranges from 0 (no numbness) to 10 (severe numbness). | Up to 4 months | 
| Change in tingling as assessed by the Brief Pain Inventory | Tingling will be assessed using the revised Brief Pain Inventory (BPI). The scale ranges from 0 (no tingling) to 10 (severe tingling). | Up to 4 months | 
| Change in physical function as assessed by Patient-Reported Outcomes Measurement Information System (PROMIS) 29 | Physical function will be assessed using the subscale of physical function, Patient-Reported Outcomes Measurement Information System (PROMIS) 29. The subscale of physical function has a range of 5 (unable to function) to 20 (able to function without difficulty). | Up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of pain sensitivity as assessed by Qualitative Sensory Testing (QST) | Pain sensitivity will be measured by QST. The QST battery consists of light touch sensation as assessed by the Semmes-Weinstein Monofilament Test (SWMT), threshold and tolerance, temporal summation, and conditioned pain modulation (CPM). The threshold responses will be conducted in randomized and counterbalanced order; CPM will always occur last. Temporal summation measures, CPM, and after-sensation responses to these measures will be combined to create the central sensitization index for use in statistical analyses. | Up to 4 months | 
| Change of brain activity as assessed by fMRI Neuroimaging | All Functional magnetic resonance imaging (fMRIs) will be acquired on a 3.0 Tesla Siemens Prisma System (Siemens Medical Solutions, Erlangen, Germany) at The Johns Hopkins Hospital Radiology Building, Baltimore. Blood Oxygen Level Dependent functional images will be acquired using 2D gradient echo echo-planar imaging to cover the whole head [repetition time (TR)=2000ms, echo time (TE)=30ms, flip angle 90 degrees, acquisition matrix 64x64x40, slice thickness 4mm]; 300 volumes will be acquired for each fMRI data point. All imaging systems are connected to the hospital picture archiving and communication system. Each scan will take approximately 20 minutes. The investigator will report the functional connectivity networks of the Pearson correlation coefficient which ranges from 0 (no correlation) to 100 (perfect correlation). | Up to 1 month | 
| Change in anti-inflammatory cytokines as assessed by serum cytokine biomarkers | A 15-mL blood sample will be drawn at each time point and blood samples will be collected using standard phlebotomy procedures and will be transferred and processed at the Johns Hopkins School of Nursing (JHSON) basic science laboratory (coagulation and serum separation by centrifugation). Serum will be stored at -80 °C at the JHSON. Once the study collection is completed, a panel of cytokines will be measured in diluted samples using the bio-plex pro-human chemokine panel. The investigator will report the number of participants that have a change in any anti-inflammatory cytokines level greater than 50 percent of baseline | Up to 4 months | 
| Change in pro-inflammatory cytokines as assessed by serum cytokine biomarkers | A 15-mL blood sample will be drawn at each time point and blood samples will be collected using standard phlebotomy procedures and will be transferred and processed at the Johns Hopkins School of Nursing (JHSON) basic science laboratory (coagulation and serum separation by centrifugation). Serum will be stored at -80 °C at the JHSON. Once the study collection is completed, a panel of cytokines will be measured in diluted samples using the bio-plex pro-human chemokine panel. The investigator will report the number of participants that have a change in any pro-inflammatory cytokine level greater than 50 percent of baseline | Up to 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acupressure, chemotherapy induced neuropathy, auricular acupressure