Acupuncture for Chemo-Induced Peripheral Neuropathy (CIPN) in Multiple Myeloma (MM) Patients- A Randomized Controlled Trial
Phase: NA
Conditions: Chemotherapy-induced Peripheral Neuropathy
Sponsor: Wake Forest University Health Sciences

 
Protocol: LCI-SUPP-MYE-ACUP-001 
Version 4: 04/21/2023 
 
Protocol #: LCI-SUPP-MYE-ACUP-001 
TITLE: Acupuncture for Chemo-Induced Peripheral Neuropathy (CIPN) in Multiple 
Myeloma (MM) Patients- A Randomized Controlled Trial 
 
Coordinating Center: 
Levine Cancer Institute 
1021 Morehead Medical Drive 
Charlotte NC, 28204 
 
Sponsor-Investigator: 
Shamille Hariharan, MD 
Department of Supportive Oncology 
Levine Cancer Institute 
1021 Morehead Medical Drive 
Charlotte NC, 28204 
Phone: 980-442-2500 
Shamille.Hariharan@atriumhealth.org 
 
Statistician: 
Jim Symanowski, PhD 
Department of Cancer Biostatistics 
Levine Cancer Institute 
1021 Morehead Medical Drive 
Charlotte NC, 28204 
Phone: 980-442-2371 
James.Symanowski@atriumhealth.org 
 
 
Trial Supported by: 
Carolinas Myeloma Research Fund  
 
The study will be conducted in compliance with the protocol, ICH/GCP and any applicable 
regulatory requirements. 
 
 
 
Throughout this document, symbols indicating proprietary names (®, TM) are not displayed. 
Hence, the appearance of product names without these symbols does not imply that these names 
are not proprietary. 
 
Confidential 
The information provided in this document is strictly confidential and is intended solely for the 
guidance of the clinical investigation. Reproduction or disclosure of this document - whether in part 
or in full - to parties not associated with the clinical investigation, or its use for any other purpose, 
without the prior written consent of the Sponsor-Investigator is not permitted. 

 
Protocol: LCI-SUPP-MYE-ACUP-001 
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PROTOCOL SIGNATURE PAGE 
 
PROTOCOL TITLE: LCI-SUPP-MYE-ACUP-001: Acupuncture for Chemo-Induced 
Peripheral Neuropathy (CIPN) in Multiple Myeloma (MM) Patients- A Randomized, 
Controlled Trial 
  
 
  
 
The signature below constitutes the approval of this protocol and the attachments and provides 
the necessary assurances that this trial will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable U.S. federal regulations and ICH guidelines. 
 
 
 
 
 
 
 
___________________________________  
_____________________ 
Signature of Sponsor-Investigator 
 
 
Date 
 
 
_____Shamille Hariharan, MD____________ 
 
Sponsor-Investigator Name (printed) 
 
 
 
 
 

 
Protocol: LCI-SUPP-MYE-ACUP-001 
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II
 
SYNOPSIS 
TITLE 
Acupuncture for Chemo-Induced Peripheral Neuropathy (CIPN) in Multiple 
Myeloma (MM) Patients- A Randomized, Controlled Trial 
STUDY POPULATION 
Adult Multiple Myeloma patients with CIPN  
SUMMARY OF STUDY 
RATIONALE 
Multiple Myeloma (MM) is a blood cancer of the plasma cells. Treatment for 
MM includes bortezomib and bortezomib combination chemotherapy which 
causes Chemotherapy-Induced Peripheral Neuropathy (CIPN) in 
approximately 30% of patients. CIPN is characterized by sensory symptoms 
including tingling, numbness, burning, weakness, pain, and aching in the 
hands and/or feet. Individuals with CIPN experience reduced quality of life 
(QOL) due to poor physical function, greater disability, falls, reduced 
functioning, and dose limiting or early discontinuation of anti-cancer 
treatment. Treatments for CIPN typically include concomitant medications, 
(e.g., gabapentin, duloxetine) yet these approaches have limited evidence to 
support clinical use, have side effects, and are not universally effective. 
Previous research suggests acupuncture is effective in treating CIPN in other 
populations with few side effects, yet the effect of acupuncture on CIPN 
among MM patients is poorly understood. 
STUDY DESIGN  
This study is a randomized, controlled trial in which subjects will be assigned 
2:1- 2 to acupuncture intervention to 1 standard subject care. Those assigned to 
acupuncture will receive a total of 12 sessions over approximately 10 weeks. 
During the first two weeks, acupuncture will occur twice per week and during 
weeks 3-10 acupuncture will occur once per week. All subjects will be 
assessed for sociodemographic and medical characteristics, neuropathy on a 
scale from 0=no neuropathy– 10=worst possible neuropathy, the FACT-GOG-
NTX scale on CIPN symptoms, physical, social/family, emotional, and 
functional well-being, other specific symptoms, quality of life, and opioid and 
concomitant medication intake. Assessments will occur at Baseline, Midpoint, 
and Endpoint over the approximately 10 weeks subjects will be on study. 
Comparisons will be made between the intervention and control groups.  
 
OBJECTIVES 
Primary Objective: 
To evaluate the effectiveness of acupuncture plus standard subject 
management versus standard subject management in terms of reduction of 
neuropathy in multiple myeloma subjects being actively treated with 
bortezomib diagnosed with CIPN or multiple myeloma subjects who have 
discontinued bortezomib within the past 12 months but continue to have 
CIPN (even if they have started new therapy that could cause neuropathy).  
Neuropathy will be subject reported using an 11-point scale from 0-No 
Neuropathy to 10-Worst Possible Neuropathy.  
 
Secondary Objectives: 
• To compare subjects with and without acupuncture for the following 
symptoms assessed by the FACT-GOG-NTX questionnaire: 

 
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III
• Specific features of CIPN utilizing the NTX sub-scale (e.g. 
numbness, tingling) 
• Nausea 
• Sadness 
• Nervousness 
• Sleep quality 
• Lack of energy 
• Pain. 
 
• To compare subjects with and without acupuncture for the following 
symptoms assessed by an adaptation of the FACT-GOG-NTX 
questionnaire: 
• Constipation 
• Dizziness 
• Dry mouth. 
 
• To compare Quality of Life in subjects with and without acupuncture 
using the CDC HRQoL-4 questionnaire. 
 
Safety Objective: 
• To summarize adverse events of special interest for subjects receiving 
acupuncture intervention 
 
Exploratory Objectives: 
To compare subjects with and without acupuncture for:  
• Opioid use, defined by Morphine Equivalent Daily Dose 
(MEDD) 1 
• Concomitant medication use, including gabapentin, duloxetine, 
pregabalin, etc.   
• To evaluate whether there is a dose response based on the 
amount of acupuncture delivered, defined by the number of 
attended acupuncture sessions from 0 to 12 for those 
randomized to the acupuncture arm.  
 
• To evaluate the effect of acupuncture expectancy for subjects 
receiving acupuncture intervention 
 

 
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IV
KEY INCLUSION 
CRITERIA  
• Age ≥ 18 years at the time of consent 
• Subject has diagnosis of multiple myeloma (any stage)  
• Currently being treated with bortezomib or bortezomib-combination 
chemotherapy; also allowed are those subjects who have discontinued 
bortezomib within the past 12 months but continue to have CIPN (even 
if they have started new therapy that could cause neuropathy)  
• ECOG Performance status of 0-3      
• Life expectancy of ≥ 12 weeks 
• Subject reported Neuropathy score of ≥2  
• No planned hospital admission within the expected time frame of study 
participation. For potential participants with a transplant in their current 
MM treatment plan:  Post-transplant subjects may enroll when 
recovered sufficiently from the transplant, i.e. platelets >50 x 103/uL, 
ANC> 0.5 x 103/uL, and ECOG performance status is 0-3. 
KEY EXCLUSION 
CRITERIA  
 
• Subjects with neuropathy pain as a result of any other cause other than 
chemotherapy  
• Subjects with needle phobia  
• Previous diagnosis of amyloidosis or POEMS syndrome 
• Documented local infection at or near the planned acupuncture sites 
(see Appendix A) 
• Subjects with metastatic involvement of the nervous system/active 
central nervous system disease 
• Plan to receive Healing Touch or Oncology Massage during study 
participation 
• Have received acupuncture within 30 days prior to enrollment  
STATISTICAL 
CONSIDERATIONS 
 
This study is designed with a primary objective to evaluate the effectiveness of 
acupuncture versus standard subject management in terms of reduction of 
neuropathy in actively treated multiple myeloma subjects diagnosed with 
CIPN. A Fisher’s Exact Test with a 20% two-sided significance level will have 
80% power to detect the difference between a standard of care group 
proportion of 0.10 and a treatment group proportion of 0.35 when the sample 
sizes are 22 and 44, respectively.  
 
NUMBER OF SUBJECTS 66 evaluable (It is estimated that a total of 75 subjects may be enrolled to 
achieve 66 evaluable subjects) 
 
 
 

 
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V
SCHEMA 
 
Recruitment of N=66 evaluable Multiple Myeloma (MM) patients currently treated with 
Bortezomib or Bortezomib-combination chemotherapy with chemo-induced peripheral 
neuropathy (CIPN); also allowed are those subjects who have discontinued bortezomib within 
the past 12 months but continue to have CIPN (even if they have started new therapy that could 
cause neuropathy) 
 
 
 
 
 
 
 
     RANDOMIZE 2:1- 
   (2 to acupuncture for every 1 control) 
 
 
 
Intervention 
↓ 
 
 
 
 
 
  
Assessments at baseline, Week 5 ± 1 week (midpoint) and Week 10 ± 1 week (endpoint) 
• 
Acupuncture Expectancy Scale (Baseline only, those randomized to 
acupuncture) 
• Neuropathy 0-10  
• Neuropathy physical location  
• FACT-GOG-NTX 
• Other symptoms (constipation, dizziness, dry mouth) 
• CDC HRQOL-4  
• Opioid Intake 
• Concomitant Medication Intake 
• Assess for AESIs 
• Collect chemotherapy regimen  
• MM status (Baseline only) 
 
 
 
 
 
 
Acupuncture Intervention N=44 
• Wks. 1-2: twice per wk.  
• Wks. 3-10: once per wk. 
• 12 total sessions over 
approximately 10 wks. 
• Will also continue SOC 
Control N=22 
 
• Standard of care 
 
• 
Informed Consent 
• 
Neuropathy 0-10 Score: 
if Score is ≥2, continue 
with Eligibility. If 
Eligible, Randomize 
subject.  
If Neuropathy score 
is <2, subject will be a 
Screen Failure 

 
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VI
TABLE OF ABBREVIATIONS 
 
Abbreviation 
Spelled out abbreviation 
AE 
Adverse event 
AESI 
Adverse event of special interest 
BIPN 
Bortezomib-induced peripheral neuropathy 
CIPN 
Chemotherapy-induced peripheral neuropathy 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTMS 
Clinical Trial Management System 
ECOG 
Eastern Cooperative Oncology Group 
EMR 
Electronic medical record 
ESAS 
Edmonton Symptom Assessment Scale 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
LCI 
Levine Cancer Institute 
MEDD 
Morphine Equivalent Daily Dose 
MM 
Multiple myeloma 
QOL 
Quality of life 
SOPS 
Standard operating procedures 
STRICTA 
Revised Standards for Reporting Interventions in Clinical Trials of 
Acupuncture 
UAP 
Unanticipated problems 
 

 
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VII
 
TABLE OF CONTENTS 
SYNOPSIS .................................................................................................................................... II 
SCHEMA ...................................................................................................................................... V 
1. 
BACKGROUND AND RATIONALE ............................................................................. 9 
1.1 
Background .......................................................................................................................... 9 
1.2 
Study Rationale and Study Design .................................................................................... 11 
2. 
STUDY OBJECTIVES .................................................................................................... 12 
2.1 
Objectives .......................................................................................................................... 12 
3. 
SUBJECT SELECTION ................................................................................................. 13 
3.1 
Subject Identification and Recruitment ............................................................................. 13 
3.2 
Inclusion Criteria ............................................................................................................... 13 
3.3 
Exclusion Criteria .............................................................................................................. 14 
3.4 
Screen Failures ................................................................................................................... 15 
4. 
SUBJECT ALLOCATION ............................................................................................. 15 
4.1 
Randomization ................................................................................................................... 15 
5. 
STUDY PLAN .................................................................................................................. 15 
5.1 
Study Intervention .............................................................................................................. 16 
5.2 
Missed Study Assessments ................................................................................................ 17 
5.3 
Sociodemographics, Medical History, Opioid and Concomitant Medication Intake ........ 17 
5.4 
Questionnaires .................................................................................................................... 19 
6. 
STUDY CALENDAR ...................................................................................................... 21 
7. 
ADDITIONAL INFORMATION ON STUDY PROCEDURES ................................. 23 
8. 
REMOVAL OF SUBJECTS FROM STUDY ............................................................... 24 
8.1 
Off Treatment..................................................................................................................... 24 
8.2 
Off Study ............................................................................................................................ 24 
9. 
DATA AND SAFETY MONITORING PLANS ........................................................... 25 
9.1 
Safety Monitoring .............................................................................................................. 25 
9.2 
Data Monitoring ................................................................................................................. 25 
10. 
POTENTIAL RISKS/UNANTICIPATED PROBLEMS ............................................. 26 
10.1 Adverse Events of Special Interest .................................................................................... 26 
10.2 Subject Confidentiality ...................................................................................................... 26 
10.3 Emotional Distress ............................................................................................................. 27 
10.4 Unanticipated Problems (UAP) ......................................................................................... 27 
11. 
STATISTICAL CONSIDERATIONS ........................................................................... 27 
11.1 Milestones .......................................................................................................................... 27 
11.2 Sample Size ........................................................................................................................ 27 
11.3 Endpoints ........................................................................................................................... 28 
11.4 Analysis Populations .......................................................................................................... 29 

 
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VIII
11.5 Analysis Methods............................................................................................................... 30 
12. 
STUDY COMPLETION OR TERMINATION ............................................................ 31 
12.1 Completion ......................................................................................................................... 31 
12.2 Termination ........................................................................................................................ 31 
13. 
STUDY MANAGEMENT ............................................................................................... 32 
13.1 IRB Approval ..................................................................................................................... 32 
13.2 Informed Consent............................................................................................................... 32 
13.3 Protocol Adherence ............................................................................................................ 32 
13.4 Other Protocol Deviations.................................................................................................. 33 
13.5 Retention of Records .......................................................................................................... 33 
13.6 Ethical and Legal Conduct of the Study ............................................................................ 33 
13.7 Confidentiality of Records ................................................................................................. 34 
13.8 Compliance with ClinicalTrials.gov .................................................................................. 34 
14. 
REFERENCES ................................................................................................................. 35 
15. 
APPENDICES .................................................................................................................. 40 
15.1 APPENDIX A: Acupuncture Procedure- STRICTA Guidelines and Acupuncture Site 
Locations ....................................................................................................................................... 40 
15.3 APPENDIX B: Advanced Opioid Conversion Calculator -Morphine equivalents ........... 47 
 
 

 
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1. BACKGROUND AND RATIONALE 
1.1 
Background 
 
1.1.1 Multiple Myeloma (MM) 
 
MM is a blood cancer of the plasma cells classified as a blood disorder. Plasma cells are white 
blood cells that produce antibodies to protect against disease and infection. Myeloma hinders the 
production of antibodies within the bone marrow which leads to reduced immune response and 
kidney damage. Myeloma also damages bone which leads to bone pain and fractures. 2  
 
1.1.2 Chemo- Induced Peripheral Neuropathy (CIPN) 
 
First-line treatment for MM is usually bortezomib (Velcade®) or bortezomib combination 
chemotherapy. 3-5 At Levine Cancer Institute, approximately 85% of MM patients receive 
bortezomib containing chemotherapy. Although chemotherapy is associated with improved 
survival, it is neurotoxic and causes CIPN in approximately 30% of patients.6,7  CIPN is 
characterized by sensory symptoms including tingling, numbness, burning, weakness, pain, 
aching in the hands and/or feet, 8 and neuropathic pain in more severe cases. 9 The 
pathophysiological mechanisms of CIPN are complex and multi-factorial which include 
oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration, 
membrane remodeling, and neuroinflammation. 10 Bortezomib-induced peripheral neuropathy in 
MM patients usually presents within the first five cycles of treatment. 11 
 
Depending on the severity of CIPN, the dose of bortezomib may be reduced or discontinued to 
avoid debilitating side-effects. Dose reductions and discontinuation of treatment negatively 
impact the treatment’s ability to prolong life. 11 Individuals with CIPN experience reduced 
quality of life (QOL) due to poor physical function, greater disability, falls, and reduced 
functioning. 12-15 CIPN may last for years past treatment and is sometimes permanent. 16  
 
1.1.3 Current Treatments for CIPN 
 
There are no cures for CIPN; it can only be treated. 17 Treatments for CIPN include concomitant 
medications which target various pathophysiological mechanisms. Pharmacologic options 
include anticonvulsants (e.g., gabapentin, (Neurontin®, Gralise®), antidepressants (e.g., 
duloxetine (Cymbalta®)), over-the-counter (e.g. aspirin, ibuprofen),prescription (e.g., celecoxib 
(Celebrex®)), non-steroidal anti-inflammatory drugs (NSAIDs), and opioids in severe cases 
unresponsive to other treatments. Topical agents (e.g., amitriptyline, lidocaine) applied to the 
skin are also options. 18,19 These treatments, however, are not universally effective. Menthol and 
capsaicin can be used but 18  have side effects and there is limited evidence to support their 
clinical use.6 Side effects of anticonvulsants include drowsiness and dizziness, and 
antidepressants are associated with dry mouth, nausea, drowsiness, dizziness, decreased appetite 
and constipation. 20  Nonpharmacologic options with varying levels of efficacy include 
neurostimulation, exercise, nonpharmacologic menthol and capsaicin topical agents, and 

 
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10
acupuncture. 18 For patients open to integrative modalities to lessen CIPN symptoms, 
acupuncture is a promising intervention. 
 
1.1.4 Acupuncture for CIPN in Multiple Myeloma   
 
Acupuncture is a nonpharmacologic practice within Traditional Chinese Medicine that involves 
the insertion of thin needles at specific sites on the body, known as acupoints, to affect the 
body’s physical function and induce a therapeutic response. 21 Previous studies show promise for 
acupuncture’s use for peripheral neuropathy in MM, 22-25 however, sample sizes have been small 
and additional studies are needed. 26 
 
In 2011, Bao and colleagues reported the first case study of a MM patient who experienced 
significantly reduced bortezomib-induced peripheral neuropathy (BIPN) after fourteen 
acupuncture treatments. The patient had significantly reduced neuropathic pain, less requirement 
for narcotics to treat pain, and improved physical function with minimal side effects. 27 Another 
case study by Mandıroğlu, Çevik, & Aylı (2014) found complete resolution from a BIPN pain 
score of eight to zero out of ten after six months of acupuncture without any side effects. 
 
 This was followed by a case series of five patients of the same population who all received 
immediate BIPN-related pain reduction after a single acupuncture treatment. Two of the three 
patients who had at least three acupuncture sessions experienced lasting pain relief and 
functional improvement after the last acupuncture session. There were no adverse effects. 23 The 
same author team then pursued a pilot study of twenty-seven MM patients with BIPN resistant to 
other medical interventions even after bortezomib had been discontinued. Neuropathic pain was 
significantly reduced and physical function was significantly improved after ten acupuncture 
sessions over ten weeks. 25 A feasibility study of nineteen MM patients with BIPN who were 
given twenty electroacupuncture sessions over nine weeks found significantly improved pain and 
physical functioning including walking, buttoning buttons and postural stability. 24 A systematic 
review and meta-analysis of the efficacy of acupuncture for CIPN found that acupuncture can 
relieve CIPN pain and functional limitations, which warrants larger scale studies.28 
 
1.1.5 Acupuncture for Quality of Life and Other Symptoms  
 
While primarily targeting CIPN, other QOL-related symptoms may also improve with 
acupuncture. Evidence suggests depression, 29,30 fatigue, 31-33 constipation, 34 nausea, vomiting, 
35,36 sleep disturbance, 37,38 general pain, 39-42 and dry mouth 43,44 are reduced. Health-related 
quality of life (HRQOL) can be measured with the validated CDC HRQOL-4. 45,46 Studies 
indicate that those who expect that acupuncture will be beneficial tend to have better outcomes 
than those who do not believe acupuncture will have a positive effect. The expectancy effect can 
be controlled for using the validated Acupuncture Expectancy Scale. 47 
 
1.1.6 Acupuncture as Potentially Opioid and Concomitant Medication-Sparing 
 
For some patients, the therapeutic benefits of acupuncture may lead to less need for 
pharmacologic management of symptoms. In a retrospective chart review of military patients, 

 
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those who experienced acupuncture had fewer opioid prescriptions and had better symptom 
control, ability to function and improved sense of well-being. Opioid prescriptions decreased 
45%, muscle relaxants 34%, NSAIDs 43%, and benzodiazepines 14%. 48 In a small study of 35 
chronic pain patients, electroacupuncture was associated with a more rapid reduction in opioid-
like medications compared to sham electroacupuncture.49 
 
1.1.7 Safety and Patient Acceptability of Acupuncture  
 
Acupuncture is a low-cost treatment option 50,51 that is in-demand by patients. 52,53 It generally 
has very few adverse events (AEs) and is considered safe when provided by qualified 
acupuncturists. AEs can include minor bleeding, pain and/or bruising at the needling site, 
fatigue, sweating, and faintness (also called “needle shock”). 54 Serious AEs including infections, 
blood-borne diseases, and internal organ or tissue injury are rare. 55  In a study of 65,000 
treatments over six years in Japan, only 94 minor AEs were reported. 56 In a study of over 
760,000 treatments among 97,733 patients in Germany, there were 6 cases of potentially serious 
AEs including worsened depression, hypertensive crisis, asthma attack, vasovagal reaction, and 
pneumothorax. 57 Cancer patients are at higher risk for AEs than non-oncology patients. AE risk 
can be reduced by employing oncology-trained acupuncturists, following Clean Needling 
Technique (hand hygiene, using disposable needles, discarding used needles into sharps 
containers) and recommending against acupunture for those with conditions including 
neutropenia, thrombocytopenia, tumor involvement at the needling site, and other unstable 
medical conditions as determined by the acupuncturist and health care team, including 
oncologists. 55 
 
1.2   Study Rationale and Study Design 
 
This randomized, controlled trial (see Schema) is designed to evaluate the effect of acupuncture 
on CIPN, other symptoms, and potential opioid and concomitant medication sparing effects in 
comparison to standard of care management in MM subjects. We hypothesize that acupuncture 
will be associated with: 1) a clinically significant and statistically significant reduction in CIPN; 
2) statistically significant reduction of other symptoms such as nervousness and lack of energy; 
and 3) statistically significantly improved QOL at ten weeks. We also theorize that acupuncture 
will be opioid and concomitant medication sparing at ten weeks. We expect that the dose of 
acupuncture received will impact the outcomes, with higher doses of acupuncture being 
associated with better outcomes. 
 
This study is novel in that it will be, to our knowledge, 1) the largest randomized, controlled trial 
to examine the effect of acupuncture on CIPN in MM patients 2) the first to explore the impact 
of acupuncture on opioid and concomitant medication intake. 
 
This project aims to strengthen the care of persons with MM by improving quality of life (QOL) 
and ability to perform daily activities through reduced CIPN symptoms. CIPN debilitates and 
erodes QOL by preventing individuals from pursuing their normal activities of daily living. The 
features of CIPN, including physical, social/family, emotional, functional, and specific CIPN 

 
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12
symptoms, will be measured with the validated FACT-GOG-NTX. 58This project brings 
necessary attention and scientific inquiry to supportive cancer care, which is sometimes de-
prioritized behind disease treatment. 59,60 The potential for nonpharmacologic acupuncture to 
reduce CIPN and other symptoms with minimal side effects has beneficial implications for 
disease treatment. Patients with controlled symptoms are better able to tolerate life-prolonging 
treatment and avoid chemotherapy dose reductions which result from neurotoxic side effects of 
chemotherapy. 11,61,62.  
 
African Americans are twice as likely to develop MM compared to Caucasians,63,64 yet are less 
likely to receive supportive care to address side effects and QOL issues. 65,66 At Levine Cancer 
Institute, approximately one-third of MM patients are African American. Acupuncture can 
strengthen the care of persons with MM by supporting their treatment and improving QOL. This 
study may promote health equity by treating a marginalized population. While there is not an aim 
to examine disparities, it is important to highlight the vulnerability of the population. 
 
Subjects will be referred from myeloma, palliative or supportive oncology clinics at Levine 
Cancer Institute. Subjects who consent and are determined to be eligible will be randomized to 
receive either acupuncture treatment or standard of care treatment for their CIPN. Subjects’ 
sociodemographics, medical history, opioid and concomitant medication intake information will 
be collected. Subjects who are randomized to the acupuncture treatment arm will receive 12 
sessions of acupuncture over approximately 10 weeks and their CIPN will continue to be treated 
by their physician. Subjects randomized to standard of care will continue only with standard of 
care therapy per their physician for treatment of their CIPN. All subjects will complete 
questionnaires at Baseline, midpoint, and endpoint. Responses to questionnaires will then be 
analyzed towards answering the study’s objectives. 
 
2. STUDY OBJECTIVES  
2.1 
Objectives 
2.1.1 Primary Objective 
• The primary objective of this study is to evaluate the effectiveness of acupuncture plus 
standard subject management versus standard subject management in terms of reduction 
of neuropathy in multiple myeloma subjects actively treated with bortezomib diagnosed 
with CIPN or multiple myeloma subjects who have discontinued bortezomib within the 
past 12 months but continue to have CIPN (even if they have started new therapy that 
could cause neuropathy).  Neuropathy will be subject reported using an 11-point scale 
from 0-no neuropathy to 10-worst possible neuropathy.  
 
2.1.2 Secondary Objectives 
• To compare subjects with and without acupuncture for the following symptoms assessed 
by the FACT-GOG-NTX questionnaire: 
o Specific features of CIPN utilizing the NTX sub-scale (e.g. numbness, tingling) 
o Nausea 

 
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o Sadness 
o Nervousness 
o Sleep quality 
o Lack of energy 
o Pain 
 
• To compare subjects with and without acupuncture for the following symptoms assessed 
by an adaptation of the FACT-GOG-NTX questionnaire: 
o Constipation 
o Dizziness 
o Dry mouth. 
 
• To compare Quality of Life in subjects with and without acupuncture using the CDC 
HRQoL-4 questionnaire. 
 
2.1.3 Safety Objective 
• To summarize adverse events of special interest for subjects receiving acupuncture 
intervention 
 
2.1.4 Exploratory Objectives 
• Exploratory objectives are to compare subject with and without acupuncture for:  
o Opioid use, defined by Morphine Equivalent Daily Dose (MEDD) 1 
o Concomitant medication use, including gabapentin, duloxetine, pregabalin, etc.  
• To evaluate whether there is a dose response based on the amount of acupuncture 
delivered, defined by the number of attended acupuncture sessions from 0 to 12, for 
subjects randomized to the acupuncture arm.  
• To evaluate the effect of acupuncture expectancy for subjects receiving acupuncture 
intervention 
 
 
3. SUBJECT SELECTION 
3.1 Subject Identification and Recruitment 
Adult subjects will be recruited at Levine Cancer Institute (LCI).  Subjects will be recruited 
regardless of their sex, race, and ethnicity.   
3.2 Inclusion Criteria 
Subject must meet all the following applicable inclusion criteria to participate in this study: 
 
1. Written informed consent and HIPAA authorization for release of personal health 
information. NOTE:  HIPAA authorization may be included in the informed consent or 
obtained separately.  
 

 
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2. Age ≥ 18 years at the time of consent 
 
3. Subject has diagnosis of Multiple Myeloma (any stage)  
 
4. Currently being treated with bortezomib or bortezomib-combination chemotherapy OR 
subjects who have discontinued bortezomib within the past 12 months but continue to 
have CIPN (even if they have started new therapy that could cause neuropathy) 
 
5. ECOG Performance status of 0-3 
 
6.  Life expectancy of ≥ 12 weeks  
 
7. Subject-reported Neuropathy score of ≥2  
 
8. No planned hospital admission within the expected time frame of study participation. For 
potential participants with a transplant in their current MM treatment plan:  Post-
transplant subjects may enroll when recovered sufficiently from the transplant, i.e. 
platelets >50 x 103/uL, ANC> 0.5 x 103/uL, and ECOG performance status is 0-3. 
 
 
9. As determined by the enrolling physician, ability of the subject to understand and comply 
with study procedures for the entire length of the study 
3.3 
Exclusion Criteria 
Subjects meeting any of the criteria below may not participate in the study: 
 
1. Uncontrolled intercurrent illness/medical condition or psychiatric illness/social situations 
that would limit compliance with study requirements as determined by the investigator 
 
2. Subjects with neuropathy pain as a result of any other cause other than chemotherapy 
 
3. Subjects with needle phobia 
 
4. Previous diagnosis of amyloidosis or POEMS syndrome 
 
5. Documented local infection at or near the planned acupuncture sites (see Appendix A) as 
determined by the enrolling investigator 
 
6. Subjects with metastatic involvement of the nervous system/active central nervous 
system disease 
 
7. Plan to receive Healing Touch or Oncology Massage during study  
 
8. Have received acupuncture within 30 days prior to enrollment  
 

 
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3.4 
Screen Failures 
A subject who, for any reason (e.g., failure to satisfy the eligibility criteria or withdraws 
consent), terminates his/her study participation before randomization is regarded as a “screen 
failure.” All screen failures will be tracked. Reasons (e.g. specific inclusion/exclusion criteria) 
for screen failure will be recorded in the dataset. 
 
 
4. SUBJECT ALLOCATION  
4.1 Randomization  
Subjects will be randomized in a 2:1 fashion to either acupuncture plus standard subject 
management or standard of care alone and assigned a Sequence Number.  This will be 
accomplished utilizing the CTMS, whereby a list of Sequence Numbers and associated treatment 
arm assignments randomly generated prior to study activation will be uploaded by a member of 
the Levine Cancer Institute Biostatistics Core. The Sequence Number will be a four digit, 
randomly generated ID number, ranging from 0001 to 9999. A stratified block randomization 
will be utilized including the following stratification factors to reduce confounding of 
comparisons between the treatment arms: 
 
• Baseline neuropathy score (neuropathy score 2 – 6 vs 7 – 10)     
 
Blinding will not be possible within this trial because the subjects and study personnel will be 
able to decipher intervention from control based on the study activities. Those exposed to 
acupuncture will understand that they are in the intervention group and those given standard of 
care only will understand that they are in the control group. If a subject in the control group has 
an acupuncture session while enrolled, they will be discontinued from the study and all further 
assessments at that point. 
 
 
5. STUDY PLAN 
See Schema  
 
This randomized, controlled trial is designed to evaluate the effect of acupuncture on CIPN, 
other symptoms, and potential opioid and concomitant medication sparing effects in comparison 
to standard of care management in MM subjects. Enrollment in this study should not affect 
subject care in any way. Subjects will not be reimbursed for study participation; however, the 
acupuncture treatments will be covered by the study and will be at no cost to the subject. This 
study will open as a single center study at LCI Morehead.  
 
Potential participants with a transplant in their current MM treatment plan: Subjects may 
be enrolled in this study either prior to stem cell transplant or after they have completed their 
transplant. Subjects will be enrolled prior to transplant if they are able to complete the study 
prior to hospitalization for transplant. Subjects will be enrolled post-transplant if scheduling will 
not allow them to complete the study prior to hospitalization or transplant. Post-transplant 

 
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subjects may enroll when recovered sufficiently from the transplant, i.e. platelets >50 x 103/uL, 
ANC> 0.5 x 103/uL, and ECOG performance status is 0-3.  
  
Subjects will be enrolled over approximately twelve months. Each enrolled subject will be on 
study for approximately 3 to 4 months. 
 
5.1 Study Intervention 
Study subjects in the intervention arm will experience acupuncture in a group setting when 
possible to resemble the conditions of regular clinical practice at Levine Cancer Institute, 
therefore enhancing external validity and the ability to apply the conclusions of the study to 
“real-world” contexts outside of the study setting. For as long as COVID-19 is a concern, the 
acupuncture team will follow these additional safety measures: subjects will be seated at an 
appropriate distance apart and wear masks, and additional time will be allotted between sessions 
to allow for additional, thorough cleaning/sanitizing of equipment. 
 
The acupuncture sessions will begin with a more intensive, twice weekly treatment for the first 
two weeks and taper to once per week for the remaining eight weeks. This amounts to 12 total 
sessions over approximately 10 weeks. 
The acupuncture procedure and specific acupoints will be performed in accordance with the 
Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) 
guidelines 67 in Appendix A. 
 
Consenting and all conversations with subjects regarding their medical history and medications 
will be held privately. Questionnaires will also be administered privately. All subjects will be 
able to answer the questionnaires via two options: 1) on paper (in person or via certified mail) or 
2) via RedCap electronic survey. Phone contact for questionnaires is acceptable if unable to be 
completed by other stated routes. The form of questionnaire administration will be based on the 
appointment situation, needs and/ or preference of the subject, and subject access to technology 
(e.g., computer, tablet, smartphone). Subject will need to be willing to provide an active email to 
which the questionnaires can be sent to utilize the electronic survey option.   
 
Subjects randomized to the control arm will have their CIPN treated by their physician per 
standard of care. Subjects randomized to the intervention arm will begin acupuncture sessions 
within two weeks of enrollment and will continue their SOC treatment for CIPN as per their 
physician.  
 
Subjects in both the treatment arm and the control arm will complete the study questionnaires at 
protocol defined timepoints, even if bortezomib/bortezomib-combination therapy is removed 
from their treatment regimen during the study (for those on active treatment). Questionnaires 
should be completed at protocol defined timepoints even if those on the acupuncture arm have 
not received the acupuncture session on schedule or if sessions are missed. 
 

 
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5.2 
 Missed Study Assessments 
 If data from questionnaires are missing, when possible, the reason for the missing data will be 
categorized and documented as follows: 
• subject felt too ill; 
• clinician or nurse felt the subject was too ill; 
• subject felt it was inconvenient or took too much time; 
• subject felt it was a violation of privacy; 
• subject didn't understand the actual language or was illiterate; 
• administrative failure to distribute the questionnaire; 
• not required at this time point; 
• other, specify; 
• unknown 
 
5.3 
Sociodemographics, Medical History, Opioid and Concomitant Medication Intake  
The electronic medical record (EMR) will be consulted to abstract demographic, medical history, 
opioid and concomitant medication data. Subjects will be asked to verify and add any 
information about their demographics, medical history, opioid and concomitant medications. 
 
5.3.1 Sociodemographics  
The sociodemographic information to be collected at baseline only includes:  
o Age  
o Sex 
o Race/ethnicity 
o Health insurance type 
o Home environment (e.g., lives alone/independent, lives with spouse/partner, lives 
with children) 
o Marital status 
o Employment status 
o Zip code 
 
5.3.2 Medical History 
The medical history information to be collected at baseline only, includes:  
o Peripheral (sensory) neuropathy Grade by CTCAE 5.0 criteria68 (only if recorded in 
medical record) 
o MM diagnosis date and staging 
o ECOG performance status69  
o Body mass index (BMI) calculated by height and weight  
o History of diabetes (excluding gestational diabetes) 
o Cardiovascular disease 
o Chronic kidney disease 
o Vertebral fractures 

 
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o Current chemotherapy regimen and all bortezomib/bortezomib-combination treatment 
given prior to enrollment 
 
5.3.3 Opioid Intake 
The electronic medical record will be consulted for opioids in the opioid medication list and 
verified with the subject. Subjects will be asked if there are any other opioids they are taking 
which might not be documented in the EMR. This information will be collected at the baseline, 
midpoint and endpoint visit. Subjects will be asked to provide the information based on a past 7-
day recall. The self-reported quantities will be converted to Morphine Equivalent Daily Dose 
(MEDD), using an opioid conversion calculator (See Appendix B). 
 
These opioids include but are not limited to: 
• fentanyl (such as Fentora®) 
• hydromorphone (such as Dilaudid®) 
• long-acting hydromorphone (Exalgo®) 
• oxycodone (such as Oxycontin®) 
• oxycodone with acetaminophen (such as Percocet®) 
• oxymorphone (such as Opana®) 
• hydrocodone with acetaminophen (such as Vicodin®, Hycet® ) 
• tramadol (such as Ultram®, Conzip®) 
• morphine (such as MS-Contin®) 
• methadone (such as Methadose, Dolophine®) 
 
5.3.4 Concomitant Medication Intake 
The electronic medical record will be consulted for concomitant medications as listed below and 
verified with the subject. Subjects will be asked if there are any other concomitant medications 
(including over-the-counter medications) which might not be documented in the EMR. This will 
be asked and collected at the baseline, midpoint, and endpoint visit. Subjects will be asked to 
provide the information based on a past 7-day recall. 
 
These concomitant medications include but are not limited to: 
 
 
Prescription non-steroidal anti-inflammatory drugs   
• ketoprofen (such as Actron®, Orudis®)  
• celecoxib (such as Celebrex®)  
• meloxicam (such as Vivlodex®, Mobic®)  
 
 
Other prescription medications   
• gabapentin (such as Neurontin®, Gralise®,Horizant®)  
• duloxetine (such as Cymbalta®)  

 
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• pregabalin (such as Lyrica®)  
• venlafaxine (such as Effexor XR®)  
• amitriptyline, (such as Elavil ®, Venatrip ®) 
• doxepin (such as Silenor®, Zonalon®)  
• nortriptyline (such as Pamelor®)  
 
 
 Over the counter non-steroidal anti-inflammatory drugs (no prescription needed)  
• aspirin (such as Bayer®, Excedrin®, Bufferin®)  
• acetaminophen (such as Tylenol®)  
• ibuprofen (such as Motrin®, Advil®, Motrin IB®, Nuprin®)  
• naproxen (such as Aleve®)  
 
 
Topical treatments applied to the skin   
• Capsaicin creams  
• Lidocaine patches or gel 
 
Note: Collect any other medications the subject identifies for management of CIPN symptoms 
 
5.4 
Questionnaires 
Questionnaires will be administered privately, preferably prior to the acupuncture session for 
those on intervention arm. All subjects will be able to answer the questionnaires via two options: 
1) on paper (in person or via certified mail) or 2) via RedCap electronic survey. Phone contact 
for questionnaires is acceptable if unable to be completed by other stated routes. The form of 
questionnaire administration will be based on the appointment situation, needs and/ or preference 
of the subject, and subject access to technology (e.g., computer, tablet, smartphone).  
 
Questionnaires to be completed at Baseline, midpoint and endpoint visits, even if those on the 
acupuncture arm have not received the acupuncture session on schedule or if sessions are missed.  
 
5.4.1 Acupuncture Expectancy Scale 
The validated 47 Acupuncture Expectancy Scale consists of 4 items about subjects’ expectations 
(e.g., my illness will improve a lot, my energy levels will increase) of the effects of acupuncture 
on a 5-point Likert-type scale from 1=not at all agree to 5=completely agree. Higher scores 
indicate greater expectations for the impact of acupuncture. Previous research suggests those 
who expect that acupuncture will be beneficial have better outcomes than those who are skeptical 
about the effect of acupuncture. This scale is appropriate only for those subjects randomized to 
the intervention acupuncture arm and will be performed only once- after Randomization but 
prior to the first acupuncture session. 
 

 
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5.4.2 Neuropathy 0-10 
The primary outcome measure is subject-reported global ‘neuropathy’ right now, measured on an 
11-point scale modeled after the Edmonton Symptom Assessment (ESAS) 70 from 0=no 
neuropathy -10= worst possible neuropathy. This measure is of unknown validity, although it 
has been used in previously published studies on CIPN. 23,71 For clarity, subjects are provided 
with a definition of neuropathy with symptom descriptors.  
 
5.4.3 Neuropathy Physical Location 
Subjects will be asked about the physical location of their neuropathy, with options hands/arms 
only, feet/legs only, both hands/arms and feet/legs, throughout the body, and other with a write-
in line. (This question is included on the Neuropathy 0-10 questionnaire) 
 
5.4.4 FACT-GOG-NTX 
The validated 58 FACT-GOG-NTX questionnaire consists of 39 total items with a 7-day recall 
period on a 5-point Likert-type scale from 0=not at all to 5=very much. The questions address 
CIPN-specific symptoms (e.g., I have numbness or tingling in my hands, I have trouble 
buttoning buttons), physical well-being (e.g., I have a lack of energy), social/family well-being 
(e.g., I feel close to my friends), emotional well-being (e.g., I feel sad, I am satisfied with how I 
am coping with my illness), and functional well-being (e.g., I am able to work including work at 
home). This questionnaire has been previously used with myeloma patients. 62  
 
5.4.5 Other Symptoms 
The FACT-GOG-NTX covers multiple symptoms of interest (i.e. nausea, sadness, nervousness, 
sleep quality, lack of energy, and general pain), however there are additional symptoms that will 
be examined in the current study. To avoid duplication and reduce respondent burden, only those 
symptoms not covered in the FACT-GOG NTX will be asked about separately. These are 
constipation, dizziness, and dry mouth. 72 These will be assessed with the same 7-day recall 
period on a 5-point Likert-type scale from 0=not at all to 5=very much as the FACT-GOG-NTX 
to make the symptoms comparable. This is a self-created measure of unknown validity. 
 
5.4.6 CDC HRQOL-4  
The CDC HRQOL-4 is a validated 45,46 four-item questionnaire used to measure health related 
quality of life (HRQOL). The first question asks about general health with response options 
excellent, very good, good, fair, and poor. The remaining three questions ask about the number 
of days in the past 30 days that the respondent was in poor physical health, poor mental health, 
and was unable to do their usual activities. This questionnaire has been used in the Behavioral 
Risk Factor Surveillance System (BRFSS) since 1993, the National Health and Nutrition 
Examination Survey (NHANES) from 2000-2012, and the Medicare Health Outcome Survey 
(HOS) since 2003. 73  
 
 

 
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6. STUDY CALENDAR 
Key to Footnotes  
1   First acupuncture session to occur within 2 weeks of enrollment (date randomized). Acupuncture treatment schedule to start on a Monday or Thursday only.  
2 Week 1 for subjects on the acupuncture/intervention arm is the week when the first acupuncture session occurs. Window for acupuncture sessions during Week 1 and Week 2 is 
at least 1 day (minimum) and no more than 8 days (maximum) between visits. Window for sessions during Weeks 3-10 is at least 2 days (minimum) and no more than 9 days 
(maximum) between visits. During Week 1 and Week 2, if an acupuncture session is missed, it may be made up the following week (there will be 3 sessions that following week). 
During Weeks 3-10, no sessions will be made up if missed. 
Procedures/Assessments   
 
Screening 
Visit 
Baseline 
(complete within 2 
weeks from 
consent, can be 
done at screening 
AFTER 
Randomization) 
 
Weeks 1-22: 
Twice per 
week 
 
Weeks 3-102: 
Once per 
week 
Week 5 ± 1  
week 3,5  
Midpoint 
Week 10 
± 1  
week3,5 
Endpoint 
 
Early 
Termination 
(if 
applicable)7 
 
Follow Up 
(30 days 
[+7] from 
last Acup 
tx) 
Informed Consent Form 
X 
 
 
 
 
 
 
 
Randomization via CTMS (within 2 
weeks from consent) 
 
X12 
 
 
 
 
 
 
Sociodemographics & Medical History 
(see 5.3.1 and 5.3.2) 
 
X 
 
 
 
 
 
 
Multiple Myeloma status6 
 
X 
 
 
 
 
 
 
ECOG 
X 
 
 
 
 
 
 
 
Height / Weight/ BMI 
 
X 
 
 
 
 
 
 
Acupuncture Expectancy Scale4  
 
X4 
 
 
 
 
 
 
Acupuncture Treatment1,2 
 
 
X2 
X2 
 
 
 
 
Collect Chemotherapy regimen 
information10 
X 
 
 
 
 
X 
X 
 
Adverse Events of Special Interest8  
 
 
Continuously, starting at First Acupuncture session  
X 
X13 
CIPN:     Neuropathy 0-10 & 
neuropathy physical location 
X11 
 
 
 
X 
X 
X 
 
CIPN:     FACT-GOG-NTX  
 
X14 
 
 
X 
X 
X 
 
Other Symptoms: Constipation, 
dizziness, dry mouth 
 
X14 
 
 
X 
X 
X 
 
Quality of Life: CDC HRQOL-4 
 
X14 
 
 
X 
X 
X 
 
Opioid Intake/ Morphine Equivalent 
Daily Dose (see Appendix B) 
 
X9 
 
 
X 
X 
X 
 
Concomitant Medication: (See Section 
5.3.4 for which medications to collect)  
 
X9 
 
 
X 
X 
X 
 

 
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3 Questionnaires at Midpoint and Endpoint should still be collected even if subject decides to discontinue the acupuncture sessions but is willing to stay on study. Week 1 for the 
control group begins at Randomization.  
4 Acupuncture Expectancy Scale questionnaire to be collected only from subjects on Intervention (Acupuncture) arm at any time AFTER Randomization has occurred, but PRIOR 
to first acupuncture session.  
5 For acupuncture arm, Midpoint occurs at Week 5 ± 1 week from first acupuncture session, with Endpoint occurring at Week 10 ± 1 week from first acupuncture session.  For 
control arm, Midpoint occurs at Week 5 ± 1 week from Randomization with Endpoint occurring at Week 10 ± 1 week from Randomization. 
6 Collect MM date of diagnosis and staging at Baseline 
7 If a subject decides or needs to be withdrawn from the study early (all visits and acupuncture assessments, if applicable), but is willing to complete an Early Termination visit, 
subject will complete assessments a final time, and will be considered Off Study (See section 8.2). Subjects do not need to complete questionnaires if they have done so within the 
last 2 weeks.  
8 AESIs should only be collected on subjects randomized to acupuncture arm, beginning with first acupuncture session until 30 days after final acupuncture session. 
9 For collection of opioid medication intake and concomitant medications, collect what has been taken over the past 7 days.  
10 Collect chemotherapy regimen information throughout the study (if applicable).  
11 CIPN Neuropathy 0-10 & neuropathy physical location questionnaire is to be completed the first time after consenting and prior to any other baseline procedures or 
assessments to determine if the subject qualifies for enrollment into the study (see section 7.1.1).  
12 Notify subject of their randomization result. 
13Follow Up on AESIs: Can be done over the phone- this follow up for AESIs is only for subjects randomized to Acupuncture treatment arm. 
14 Questionnaire may be completed after consent and prior to or after Randomization

 
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7.  ADDITIONAL INFORMATION ON STUDY PROCEDURES 
7.1.1 Screening/Baseline 
Subjects will be consented to the trial, and the CIPN Neuropathy 0-10 (and physical location) 
questionnaire will be administered. Subjects who score <2 on the CIPN Neuropathy 0-10 
questionnaire will be a screen failure and will not be randomized or enrolled into the study. If 
CIPN Neuropathy 0-10 is answered sufficiently for inclusion (score ≥2), the rest of the baseline 
assessments are to be completed within two weeks from consent. Once eligibility is confirmed, 
subject will be randomized via CTMS to either Acupuncture (intervention arm) or Standard of 
Care. Subjects will be notified of their randomization result. Those randomized to Intervention 
Arm will begin acupuncture sessions within two weeks of enrollment. 
 
7.1.2 Midpoint and Endpoint visits 
The following assessments and questionnaires will be repeated at the Midpoint visit (Week 5 ± 1 
week) and at the Endpoint visit (Week 10 ± 1 week) from randomization for the control arm. The 
assessments and questionnaires will be completed for the acupuncture arm at Midpoint visit  
(Week 5 ± 1 week) and Endpoint (Week 10 ± 1 week) from first acupuncture session.  The 
questionnaires (see section 5.4) will be administered either in the clinic or via electronic survey 
or certified mail. The questionnaires should be completed with subjects in both arms, and 
regardless of whether the intervention (acupuncture) was received. Subjects in both arms will 
complete the study questionnaires at protocol defined timepoints, even if 
bortezomib/bortezomib-combination therapy is removed from their treatment regimen during the 
study (for those on active bortezomib treatment). 
 
Note: These same assessments and questionnaires will be performed if the subject has an Early 
Termination visit (see study calendar).  
 
See section 5.4 for more detailed information on the study questionnaires. 
 
• Collect AESI information, if applicable (for those on acupuncture arm) 
• Collect chemotherapy regimen information.  
• CIPN: Neuropathy 0-10   
• CIPN: Neuropathy physical location  
• CIPN: FACT-GOG-NTX 
• Other symptoms (constipation, dizziness, dry mouth) 
• CDC HRQOL-4 
• Morphine Equivalent Daily Dose (Past 7-day recall) 
• Concomitant medication intake (Past 7-day recall) 
 
7.1.3 Collection of AESIs  
Subjects on the Intervention arm will be asked specifically at the Midpoint and Endpoint 
timepoints if they have had any of the designated AESIs. If subject happens to report an AESI or 

 
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if there is documentation in the EMR of an AESI at any other time during the study, starting at 
first acupuncture session, the study team will collect this information. See Section 10.1 for 
further details including timeframe for collection of AESIs. 
7.1.4 Acupuncture 
The acupuncture procedure and specific acupoints will be performed in accordance with the 
Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) 
guidelines 67 in Appendix A. Acupuncture in this study will occur twice during weeks 1-2, then 
once weekly during weeks 3-10. During Week 1 and Week 2, if an acupuncture session is 
missed, it may be made up the following week (there will be 3 sessions that following week). 
During Weeks 3-10, no sessions will be made up if missed. The date of acupuncture sessions 
completed and acupoints received will be documented. Subjects may continue to receive 
acupuncture sessions per protocol even if bortezomib or bortezomib-combination treatment is 
discontinued. Subjects should continue per protocol acupuncture sessions even if their 
neuropathy resolves. 
 
8. REMOVAL OF SUBJECTS FROM STUDY 
8.1 Off Treatment 
If subjects on the acupuncture arm decide to discontinue the acupuncture sessions but continue 
the questionnaires and other assessments, they will be considered Off Treatment. Reasons for 
coming off treatment would include, but not be limited to: 
• Completed protocol therapy 
• Adverse event (toxicity) 
• Non-compliance 
• Investigator decision 
• Consent withdrawal for acupuncture sessions 
• Subject death 
• Study closure 
 
8.2 Off Study 
Once all on-study assessments and procedures are completed, subject will be considered Off 
Study. Subjects on the acupuncture arm will be followed for AESIs for 30 days post the last 
acupuncture session, then they will be Off Study. 
 
Subjects may stop their participation in this study at any time if they no longer wish to 
participate, or if the investigator believes this to be in the best interest of the subject.  
When subjects are removed from the study, the reason for study removal and date the subject 
was removed should be documented. Reasons a subject may be removed from study include, but 
are not limited to: 
• Subject non-compliance with study participation, in the opinion of the investigator  
• The subject withdraws study consent 
• The subject is lost to follow-up 
• Investigator’s decision to withdraw the subject 

 
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• Subject death 
 
Subjects that are Off Study will not participate in any study related procedures, including data 
collection. 
 
 
9. DATA AND SAFETY MONITORING PLANS 
9.1 
Safety Monitoring 
This protocol will be monitored according to the processes in effect for all LCI investigator-
initiated studies and the protocol-specific monitoring plan and will abide by standard operating 
procedures (SOPs) set forth by both Atrium Health Office of Clinical and Translational Research 
and the LCI Clinical Trials Office.  It is the responsibility of the Sponsor-Investigator to monitor 
any safety data (i.e., unanticipated problems/potential risks as per Section 9) for this study.  The 
Sponsor-Investigator, Statistician, and other team members as needed will meet regularly to 
monitor subject consents, enrollment and retention, safety data, and validity/integrity of the data. 
Documentation of these meetings will be kept with the study records. The Sponsor-Investigator 
will submit data to the LCI Data and Safety Monitoring Committee as required. 
  
9.2 
Data Monitoring 
This study will be organized, performed, and reported in compliance with the study protocol, 
SOPs of the LCI and Atrium Health Office of Clinical and Translational Research (and/or other 
participating institutional SOPs), and other applicable regulations and guidelines (e.g. GCP).  
 
Subjects will be monitored by LCI Quality Assurance Monitors per the study-specific monitoring 
plan and LCI/Atrium Health SOPs for data quality. Data from this study will be collected on 
electronic case report forms (eCRFs) and stored in the study database. Monitoring will be done 
by comparing source documentation to the eCRFs. Any variation between the two data sets will 
be discussed with the investigator, Sponsor-Investigator and/or other study team members as 
appropriate.  
 
The study database will be reviewed and checked for omissions, apparent errors, and values 
requiring further clarification using computerized and manual procedures. Data queries requiring 
clarification will be generated and addressed by the appropriate study team member. Only 
authorized personnel will make corrections to the study database and all corrections will be 
documented in an electronic audit trail. 
 
It is important for the investigators and their relevant personnel to be available during the 
monitoring visits and for sufficient time to be devoted to the process. 
 

 
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10. POTENTIAL RISKS/UNANTICIPATED PROBLEMS  
10.1 Adverse Events of Special Interest  
 Adverse Events of Special Interest will be collected only for those subjects on the intervention 
arm, beginning with start of first acupuncture session. AESIs will be collected through 30 days 
post last acupuncture session. Subjects who experience an AESI will be medically managed by 
their physician or acupuncturist through standard of care, as appropriate. These events should 
only be captured if deemed related to the acupuncture intervention per the Investigator. 
 
All AESIs will be graded per CTCAE 5.0. 
10.1.1 Acupuncture Site AESI 
Potential adverse events that may occur at the acupuncture site to be documented and followed in 
this study are: 
• Bleeding, Grade ≥2; (Use “General disorders and administration site conditions, other, 
specify: “bleeding”)  
• Bruising, Grade ≥1 
• Skin Infection, Grade ≥1 
• Edema, localized, Grade ≥2 
• Dry Skin, Grade ≥2 
• Urticaria (hives), Grade ≥1 
• Pruritus (itching), Grade ≥1 
• Rash, maculopapular, Grade ≥1 
• Pain, Grade ≥2 
• Flushing, Grade ≥2 
 
10.1.2 Other AESI 
Other potential adverse events to be documented and followed in this study are noted below. 
However, these should only be captured if they are deemed related to the acupuncture 
intervention per the Investigator.  
• Dizziness, Grade ≥2 
• Syncope, Grade ≥3 
• Fatigue, Grade ≥2 
• Hyperhidrosis, (Sweating) Grade ≥2 
 
10.2 Subject Confidentiality 
We do not anticipate any breach of confidentiality as no records will be shared with any 
personnel outside the research team.  All medical information including assessments and other 
medical records will be recorded and stored in a database. The database will exist on a password 
protected secured server. Medical records data will be abstracted by the Research Designee. All 
records will be kept confidential.  

 
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10.3 Emotional Distress 
Some questions in the questionnaires could create emotional distress or confusion.  If a subject 
experiences distress or confusion, the questionnaire process will be interrupted or discontinued, 
and the Research Designee will follow-up with the Sponsor-Investigator. 
10.4 
Unanticipated Problems (UAP) 
10.4.1 Definition 
A UAP is any incidence, experience or outcome that is unexpected (e.g., a lost or stolen laptop 
computer that contains sensitive study information) given the information provided in research-
related documentation (e.g., informed consent) and the study population characteristics, that is 
related or possibly related to participation in the research study and places the participant at an 
increased risk.  
10.4.2 Reporting 
All UAPs occurring during the conduct of a protocol and meeting the definition of a UAP will be 
reported to the Sponsor-Investigator and IRB per IRB reporting requirements.  
 
11. STATISTICAL CONSIDERATIONS 
11.1 
Milestones 
11.1.1 Registration Date 
The date the subject signs the informed consent. 
11.1.2 Enrollment Date/On Study Date 
The date the subject is randomized. 
11.1.3 On Treatment Date 
For subjects randomized to the acupuncture arm, the on-treatment date will be the date of the 
first acupuncture session. 
11.1.4 Treatment Discontinuation Date 
For subjects randomized to the acupuncture arm, the treatment discontinuation date will be the 
date the investigator decides to discontinue the subject from receiving acupuncture treatment. 
See Section 8.1.  
11.2 
Sample Size 
This study is designed with a primary objective to evaluate the effectiveness of acupuncture 
versus standard subject management in terms of reduction of neuropathy in actively treated 
multiple myeloma subjects diagnosed with CIPN. A Fisher’s Exact Test with a two-sided alpha = 
0.20 significance level will have at least 80% power to detect the difference between a standard 
of care group proportion of 0.10 and a treatment group proportion of 0.35 when the sample sizes 
are at least 22 and 44 evaluable subjects, respectively. In order to identify at least 66 evaluable 
subjects, we anticipate enrolling 75 subjects. 

 
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11.3 Endpoints 
11.3.1 Definition of Primary Endpoint 
The primary endpoint for this study is a binary variable that will be determined for each subject 
indicating whether or not they experienced at least a 2-point improvement in neuropathy between 
the baseline score and the score obtained at Week 10 (+/- 1 week).   
 
11.3.2 Definition of Secondary Endpoints 
• Specific features of CIPN  
o Specific features of CIPN assessed through the NTX subscale from FACT-GOG-
NTX will be determined for each subject as a composite measure, which is 
calculated as the sum of the responses to the NTX subscale questions. For 
subjects who complete all 12 NTX subscale questions, the composite score will 
range from 0 to 48.  
• Nausea 
o Nausea assessed through question GP2 on the FACT-GOG-NTX subject-reported 
assessment will be determined for each subject as 5 level ordinal variable from 0 
= not at all to 4 = very much.  
• Sadness 
o Sadness assessed through question GE1 on the FACT-GOG-NTX subject-
reported assessment will be determined for each subject as 5 level ordinal variable 
from 0 = not at all to 4 = very much.  
• Nervousness 
o Nervousness assessed through question GE4 on the FACT-GOG-NTX subject-
reported assessment will be determined for each subject as 5 level ordinal variable 
from 0 = not at all to 4 = very much.  
• Sleep quality 
o Sleep quality assessed through question GF5 on the FACT-GOG-NTX subject-
reported assessment will be determined for each subject as 5 level ordinal variable 
from 0 = not at all to 4 = very much.  
• Lack of energy  
o Lack of energy assessed through question GP1 on the FACT-GOG-NTX subject-
reported assessment will be determined for each subject as 5 level ordinal variable 
from 0 = not at all to 4 = very much.  
• Pain  
o Pain assessed through question GP4 on the FACT-GOG-NTX subject-reported 
assessment will be determined for each subject as 5 level ordinal variable from 0 
= not at all to 4 = very much.  
• Constipation  
o Constipation assessed through additional question amended to FACT-GOG-NTX 
subject-reported assessment will be determined for each subject as a 5-level 
ordinal variable from 0 = not at all to 4 = very much.  
• Dizziness 

 
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o Dizziness assessed through additional question amended to FACT-GOG-NTX 
subject-reported assessment will be determined for each subject as a 5- level 
ordinal variable from 0 = not at all to 4 = very much.  
• Dry Mouth 
o Dry mouth assessed through additional question amended to FACT-GOG-NTX 
subject-reported assessment will be determined for each subject as a 5- level 
ordinal variable from 0 = not at all to 4 = very much.  
• Quality of Life 
o General Health assessed through CDC-HRQOL Question 1 will be calculated for 
each subject as a 5- level ordinal variable from Poor to Excellent   
o The number of unhealthy days will be calculated as the average of the number of 
physically unhealthy days (CDC-HRQOL Question 2) and the number of 
mentally unhealthy days (CDC-HRQOL Question 3), with a maximum of 30 
days. 74 This will be calculated for each subject as a quantitative value between 0 
and 30, representing the number of days out of the past 30 that the subject’s health 
was not good.  
o The number of activity limitation days assessed through CDC-HRQOL Question 
4 will be calculated for each subject as a quantitative value between 0 and 30, 
representing the number of days out of the past 30 that the subject’s health kept 
them from doing their usual activities.  
11.3.3 Definition of Safety Endpoints 
• Adverse Events of Special Interest will be determined for each subject as binary variables 
indicating whether or not they experienced an AESI. These will be determined by 
preferred term, system organ class, and overall.  
11.3.4 Definition of Exploratory Endpoints 
• Opioid use 
o Opioid use assessed through Morphine Equivalent Daily Dose (MEDD) will be 
calculated for each subject as a quantitative value.  
• Concomitant medication use 
o Concomitant medication use assessed through medication name and dose will be 
determined for each subject.   
• Acupuncture administration 
o Acupuncture administration will be defined for each subject on the acupuncture 
arm as the number of attended acupuncture sessions from 0 to 12.  
• Acupuncture expectancy  
o The acupuncture expectancy score will be captured quantitatively for each subject 
as a composite score ranging from 4 to 20.  
11.4 
Analysis Populations 
The intent to treat (ITT) population will consist of all randomized subjects. The ITT population 
will be used to summarize the CONSORT diagram, subject disposition, and baseline subject 
disease characteristics. The evaluable population will consist of enrolled subjects who have 
complete baseline and Week 10 (± 1 weeks) neuropathy scores. The evaluable population will be 

 
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used for the analyses of all primary and secondary endpoints. Additionally, an intervention-
compliant population will be defined as all subjects in the evaluable population who meet all of 
the following criteria:  
 
• Subjects randomized to the acupuncture arm who have received at least 75%, or 9 of the 
12 sessions in up to 13 weeks from randomization.  
• Subjects randomized to the control arm who have not received any acupuncture at any 
time while they are on study.   
  
The intervention-compliant population will be utilized for sensitivity analyses.  
 
11.5 
Analysis Methods 
11.5.1 Timing of Analysis 
A single and final analysis will occur after 66 enrolled subjects have been identified in the 
evaluable population.  
11.5.2 
Subject Disposition 
A summary of all consented subjects will be provided.  This will include a summary of subjects 
who consented, were enrolled, treated, discontinued treatment (including reasons), died, were 
lost to follow-up or withdrew consent. 
11.5.3 Baseline Subject Characteristics 
A summary of subject demographics will be completed and selected subject medical history will 
be assessed. 
11.5.4 Primary Analysis 
The frequency and proportion of subjects who experienced at least a 2-point improvement in 
neuropathy between the baseline score and the score obtained at Week 10 (+/- 1 week) will be 
calculated for each study arm. A two-sided Fisher Exact test will be executed, testing the null 
hypothesis that there is no difference in neuropathy improvement rate between the arms. 
Additionally, logistic regression will be used to evaluate the impact of acupuncture while 
adjusting for potential baseline confounding factors, including the stratification variable, baseline 
neuropathy severity grade. Univariate models will be used to identify baseline factors that are 
individually prognostic. Statistically significant factors identified from the univariate models will 
then be included in a multivariable model. Backward elimination will be used to identify 
baseline factors that are independently prognostic. A treatment indicator variable will be added 
to obtain an adjusted odds ratio.  
 
11.5.5 Secondary Analysis 
An analysis similar to that described in the primary analysis will be performed for scores 
obtained at 5 weeks. Additionally, a repeated measures model including a random effect for 
subject will be estimated for the binary neuropathy improvement score measured at baseline, 

 
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week 5 and week 10. Additional baseline factors as previously described above may be added to 
this model as well.   
 
The secondary endpoint composite measure of specific CIPN symptoms will be treated as a 
continuous measure and analyzed using analysis of variance techniques. The secondary 
endpoints measured on a 5-level ordinal scale will be summarized with frequencies and 
proportions and analysis of variance techniques on the ranks test will be used to test for 
differences by arm. The number of unhealthy days and activity limitation days will be analyzed 
using analysis of variance techniques.  
 
11.5.6 Safety Analysis 
Adverse events of special interest will be summarized by frequencies and proportions for 
subjects on the acupuncture intervention arm. Clopper-Pearson 95% confidence intervals will be 
estimated.  
 
11.5.7 Exploratory Analysis 
The exploratory endpoint of Morphine Equivalent Daily Dose (MEDD) will be treated as a 
continuous measure and analyzed using analysis of variance techniques. Total counts and 
descriptive statistics of class and dose of concomitant medication use will be summarized by 
study arm. 
 
In order to evaluate the dose response, dose will be treated as a categorical variable with levels of 
no acupuncture (0 sessions), low dose (1 – 3 sessions), medium dose (4 – 7 sessions), high dose 
(8 – 11 sessions) and complete dose (12 sessions). Logistic regression will be performed to 
investigate the association between dose of acupuncture and CIPN improvement. Acupuncture 
expectancy will be determined for each subject as a composite measure, which is calculated as 
the sum of the responses to the four questions on the acupuncture expectancy scale. Logistic 
regression will be used to evaluate the effect of acupuncture expectancy on the primary endpoint, 
2-point improvement in neuropathy.  
 
 
12. STUDY COMPLETION OR TERMINATION 
12.1 Completion 
The study will be considered complete when one or more of the following conditions is met: 
• All subjects have withdrawn from the study 
• All subjects have discontinued from the study 
• The IRB, LCI DSMC, or Sponsor-Investigator discontinues the study because of safety 
considerations 
• The Sponsor-Investigator defines an administrative or clinical cut-off date 
12.2 Termination 
The study will be terminated early when one or more of the following conditions occur: 

 
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• If risk-benefit ratio becomes unacceptable owing to, for example, 
o Safety findings from this study (e.g., UAPs) 
o Results of parallel clinical studies 
o If the study conduct (e.g., recruitment rate, drop-out rate, data quality, protocol 
compliance) does not suggest a proper completion of the trial within a reasonable 
time frame 
• The Sponsor-Investigator has decided to close the trial at any site and at any time 
 
For any of the above closures, the following applies: 
• Closures should occur only after consultation between involved parties. 
• All affected institutions must be informed as applicable according to local law.   
• In case of a partial study closure, ongoing subjects, including those in follow- up, must be 
taken care of in an ethical manner. 
 
13. STUDY MANAGEMENT 
13.1 IRB Approval  
The study protocol, the informed consent(s) and any other necessary documents must be 
approved by the Sponsor IRB and site(s) IRB of record in accordance with federal regulations 
and obtained prior to implementation.  
 
The Sponsor IRB and site(s) IRB of record will be informed of any amendment to the protocol, 
informed consent(s), and any other necessary documents in accordance with IRB reporting 
requirements. The study protocol will undergo continuing IRB review based on the level of risk 
as assessed by the IRB no less than annually, or as applicable, in accordance with IRB 
requirements.  
13.2 Informed Consent 
Before recruitment and screening/enrollment onto this study, the subject will be given a full 
explanation of the study, the opportunity to review the consent form, and the opportunity to have 
all their questions answered. Prior to a subject’s participation in the trial, the informed consent(s) 
will be reviewed, signed and personally dated by the subject and by the person who conducted 
the informed consent discussion. A copy of each informed consent will be given to the subject 
and each original will be placed in the subject's research record. An entry must also be made in 
the subject's dated source documents to confirm that informed consent was obtained prior to any 
study-related procedures and that the subject received a signed copy.   
 
13.3 Protocol Adherence 
Except for an emergency situation in which proper care for the protection, safety, and well-being 
of the study subject requires alternative treatment, the study shall be conducted exactly as 
described in the approved protocol.   

 
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13.3.1 Amendments to the Protocol and Informed Consent 
If it is necessary for the study protocol to be amended and/or the informed consent revised, the 
amendment or a new version of the study protocol and/or revised informed consent must be 
approved by the Sponsor-Investigator and the Sponsor IRB. 
13.4 Other Protocol Deviations  
If a deviation occurs, the event should be reported to the Sponsor-Investigator via entry in the 
CTMS within 10 business days of awareness. Any IRB reportable event that occurs must be 
reported to the IRB and to the Sponsor-Investigator as soon as possible but no later than 10 
business days of awareness. 
Protocol deviations that, in the Investigator’s judgment, potentially caused harm to participants 
or others or indicates that the participants or others are at an increased risk of harm, or has 
adversely impacted data integrity will be reported promptly to the IRB per IRB reporting 
requirements.  
Planned protocol deviations should be submitted to the Sponsor for approval prior to the 
anticipated deviation occurring. After Sponsor approval has been obtained, planned deviations 
should be submitted to the IRB prior to the anticipated deviation occurring. IRB approval must 
be obtained prior to deviation occurrence. No exceptions for eligibility criteria are not allowed. 
13.5 
Retention of Records 
Essential documentation (e.g., source documents, Sponsor-Investigator correspondence, 
monitoring reports, and regulatory documents), including all IRB correspondence, will be 
retained for at least 2 years after the investigation is completed.  Documentation will be readily 
available upon request. 
13.6 Ethical and Legal Conduct of the Study 
The procedures set out in this protocol, pertaining to the conduct, evaluation, and documentation 
of this study, are designed to ensure that the Investigator abide by GCP guidelines.  The study 
will also be carried out in full conformity with Regulations for the Protection of Human Subjects 
of Research codified in the ICH E6 and in keeping with applicable local law(s) and regulation(s). 
 
Documented approval from appropriate agencies will be obtained for all participating centers 
before the start of the study, according to GCP, local laws, regulations and organizations.  
 
Strict adherence to this protocol is required for all aspects of study conduct; the investigators 
may not modify or alter the procedures described in this protocol.   
The Sponsor-Investigator is responsible for the conduct of the trial at the sites in accordance with 
the Declaration of Helsinki.  The Sponsor-Investigator is responsible for overseeing all study 
subjects.  The Sponsor-Investigator must assure that all study site personnel, including sub-
investigators and other study staff members, adhere to the study protocol and all applicable 
regulations and guidelines regarding clinical trials both during and after study completion. 
 

 
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The Sponsor-Investigator will be responsible for assuring that all the required data will be 
collected and properly documented. 
13.7 Confidentiality of Records 
All records identifying the subject will be kept confidential and, to the extent permitted by the 
applicable laws and/or regulations, will not be made publicly available. 
 
13.8 Compliance with ClinicalTrials.gov 
The Sponsor-Investigator is solely responsible for determining whether the trial and its results 
are subject to the requirements for submission to ClinicalTrials.gov 
(http://www.clinicaltrials.gov).  
 
 

 
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Surbone A, Halpern MT. Unequal cancer survivorship care: addressing cultural 
and sociodemographic disparities in the clinic. Supportive care in cancer : official 
journal of the Multinational Association of Supportive Care in Cancer. 
2016;24(12):4831-4833. 
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MacPherson H, Altman DG, Hammerschlag R, et al. Revised STandards for 
Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): extending the 
CONSORT statement. PLoS medicine. 2010;7(6):e1000261. 
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68. 
National Institutes of Health-National Cancer Institute. Common Terminology 
Criteria for Adverse Events (CTCAE) Version 5.0. November 27, 2017. 
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69. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the 
Eastern Cooperative Oncology Group. American journal of clinical oncology. 
1982;5(6):649-655. 
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70. 
Hui D, Bruera E. The Edmonton Symptom Assessment System 25 Years Later: 
Past, Present, and Future Developments. Journal of pain and symptom management. 
2017;53(3):630-643. 
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71. 
Rostock M, Jaroslawski K, Guethlin C, Ludtke R, Schroder S, Bartsch HH. 
Chemotherapy-induced peripheral neuropathy in cancer patients: a four-arm randomized 
trial on the effectiveness of electroacupuncture. Evidence-based complementary and 
alternative medicine : eCAM. 2013;2013:349653. 
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72. 
Benyamin R, Trescot AM, Datta S, et al. Opioid complications and side effects. 
Pain physician. 2008;11(2 Suppl):S105-120. 
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73. 
Centers for Disease Control and Prevention. Health-Related Quality of Life 
(HRQOL).  https://www.cdc.gov/hrqol/hrqol14_measure.htm. Accessed March 31, 2020. 
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74. 
U.S. Department of Health and Human Services. Measuring Healthy Days: 
Population Assessment of Health-Related Quality of Life. In: Centers for Disease Control 
and Prevention, ed: National Center for Chronic Disease Prevention and Health 
Promotion, Division of Adult and Community Health; November 2000.  
 
 

 
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15. APPENDICES 
15.1 APPENDIX A: Acupuncture Procedure- STRICTA Guidelines and Acupuncture 
Site Locations 
Item  
Detail  
Specifics 
1. Acupuncture 
rationale        
    (Explanations and 
examples)  
1a) Style of acupuncture (e.g. Traditional Chinese 
Medicine, Japanese, Korean, Western medical, Five 
Element, ear acupuncture, etc)  
Traditional 
Chinese 
Medicine 
Ear Acupuncture 
points 
1b) Reasoning for treatment provided, based on 
historical context, literature sources, and/or consensus 
methods, with references where appropriate  
Symptom 
mitigation, for 
CIPN.  
Additional 
questions to field 
for positive 
systemic effect 
on common 
opioid 
symptomology 
1c) Extent to which treatment was varied  
Protocol + hand 
and/or foot points 
dependent on 
predominant 
physical CIPN 
location 
2. Details of needling   
    (Explanations and 
examples)  
2a) Number of needle insertions per subject per 
session (mean and range where relevant)  
 As needed 
2b) Names (or location if no standard name) of points 
used (uni/bilateral)  
see text in section 
7  
2c) Depth of insertion, based on a specified unit of 
measurement, or on a particular tissue level  
Typically ½” 
insertion, with 
exception of ear 
points 
2d) Response sought (e.g. de qi or muscle twitch 
response)  
Elicit mild de qi 
response in most 
acupoints 
2e) Needle stimulation (e.g. manual, electrical)  
Manual only  
2f) Needle retention time  
Min. 30 max 50 
minutes, average 
40-45 minutes 

 
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2g) Needle type (diameter, length, and manufacturer 
or material)  
diameter 
0.20mm, length 
15mm & 30mm 
3. Treatment regimen   
    (Explanations and 
examples)  
3a) Number of treatment sessions  
12 total sessions 
3b) Frequency and duration of treatment sessions  
Twice per week 
for weeks 1-2;  
once per week 
for weeks 3-10 
4. Other components 
of treatment   
    (Explanations and 
examples)  
4a) Details of other interventions administered to the 
acupuncture group (e.g. moxibustion, cupping, herbs, 
exercises, lifestyle advice)  
none 
4b) Setting and context of treatment, including 
instructions to practitioners, and information and 
explanations to patients  
Group 
acupuncture 
following 
COVID-19 
protocols 
5. Practitioner 
background   
    (Explanations and 
examples)  
5) Description of participating acupuncturists 
(qualification or professional affiliation, years in 
acupuncture practice, other relevant experience)  
Master’s level 
accredited 
acupuncturists 
with at least 8 
years of 
experience. 
6. Control or 
comparator 
interventions 
    (Explanations and 
examples)  
6a) Rationale for the control or comparator in the 
context of the research question, with sources that 
justify this choice  
The control 
condition will be 
standard of care 
for CIPN. No 
sham 
acupuncture will 
be used. 
6b) Precise description of the control or comparator. If 
sham acupuncture or any other type of acupuncture-
like control is used, provide details as for Items 1 to 3 
above.  
Standard of care 
control 
7. Specific Acupoints 
All subjects will receive the protocol’s full body 
acupoints at each session. Depending on the physical 
location of CIPN, à-la-carte acupoints can be added.  
BĀXIÉ can be added for neuropathy in the hands and 
BĀFĒNG can be added for neuropathy in the feet. If 
Neuropathy is present in both the hands and feet, 
BĀXIÉ and BĀFĒNG can be used. 
See following  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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POINTS 
LOCATION 
Full body acupuncture points given to all subjects at each session 
Ki3 – Taixi 
In the depression between the medial malleolus and the Achilles tendon, level 
with the prominence of the medial malleolus. 
 
 
Sp6 – Sanyinjiao 
On the medial side of the lower leg, 3 cun superior to the prominence of the 
medial malleolus, in a depression close to the medial crest of the tibia. 
St36 – Zusanli 
Below the knee, 3 cun inferior to Dubi ST-35, one fingerbreadth lateral to the 
anterior crest of the tibia. 

 
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St40 – Fenglong 
On the lower leg, midway between the tibiofemoral joint line (level with the 
popliteal crease) and the lateral malleolus, two finger-breadths lateral to the 
anterior crest of the tibia (i.e. one finger-breadth lateral to Tiaokou ST-38). 
PC 6 – Nèiguān 
On the flexor aspect of the forearm, 2 cun proximal to Dàlíng P-7, between the 
tendons of palmaris longus and flexor carpi radialis. 
 
LI11 – Quchi 
At the elbow, midway between Chize LU-5 and the lateral epicondyle of the 
humerus, at the lateral end of the transverse cubital crease. 
GB 34 – Yánglíngquán 
Below the lateral aspect of the knee, in the tender depression approximately 1 
cun anterior and inferior to the head of the fibula. 

 
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Ear SNS (Autonomic) 
The Sympathetic ear point is on the inside of the helix following the path of the 
lower part of the antihelix crus  
 
Ear Shenmen 
Situated at the apex of the triangular fossa 
Ear Kidney 
On the lower border of the inferior antihelix crus, equidistant and directly 
beneath Ear Shenmen (situated at the apex of the triangular fossa). 

 
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à-la-carte acupuncture points dependent on physical CIPN location  
Hands 
BĀXIÉ 
When the hand is made into a fist, six of these points lie in the depressions 
between the metacarpal heads, proximal to the web margins. The remaining two 
points lie equidistant between the thumb and index metacarpals, proximal to the 
web margins. 
Feet 
BĀFĒNG 
On the dorsum of the foot, between the toes, 0.5 cun proximal to the margin of 
the web. 

 
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15.3 APPENDIX B: Advanced Opioid Conversion Calculator -Morphine equivalents 
 
 
https://globalrph.com/medcalcs/advanced-opioid-conversions-equianalgesic-morphine-
equivalents/