Acupuncture Treatment of Chemotherapy-Induced Peripheral Neuropathy in Women With Breast or Gynecologic Cancers: Mechanisms of Action and Feasibility
Phase: NA
Conditions: Chemotherapy-induced Peripheral Neuropathy, Breast Cancer Female, Gynecologic Cancer
Sponsor: University of Utah

 
 
 
 
Acupuncture Treatment of Chemotherapy-Induced Peripheral Neuropathy in Women with Breast 
or Gynecologic Cancers: Mechanisms of Action and Feasibility 
  
IRB_00107709 
 
NCT04067544 
 
Principal Investigator 
Lisa Taylor-Swanson, PhD, MAcOM, LAc 
Assistant Professor  
College of Nursing, University of Utah  
Lisa.taylor-swanson@nurs.utah.edu  
(801) 585-5486   
 
Co-Principal Investigator 
Annie Budhathoki, DAOM, LAc  
Licensed Acupuncturist   
Wellness Education & Training Coordinator   
Huntsman Cancer Institute  
Wellness and Integrative Health Center  
Annie.budhathoki@hci.utah.edu   
(801) 587-4435    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol name: CIPN Acu 
Principal Investigator: Taylor-Swanson 
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Version 5 
 
 
 
Historical Protocol Versions 
Version 1: 12/11/18 
Version 2: 05/31/19 
Version 3: 09/03/19 
Version 4: 10/31/19 
Version 5: 11/22/19 
 

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Principal Investigator: Taylor-Swanson 
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LIST OF ABBREVIATIONS 
Abbreviation or 
Term1 
Definition/Explanation 
AE 
Adverse Event 
 
AT 
Acupuncture Treatment 
 
BPI 
Brief Pain Inventory  
 
CCAOM 
Council of Colleges of Acupuncture and Oriental Medicine  
 
CIPN 
Chemotherapy-Induced Peripheral Neuropathy 
 
CIPN-R-ODS 
Chemotherapy-Induced Peripheral Neuropathy Rasch-built Overall 
Disability Scale 
 
CNS 
Central Nervous System 
 
CNT 
Clean Needle Technique 
 
CRA 
Clinical Research Associate 
 
CTCAE 
Common Terminology Criteria for Adverse Events (from National 
Cancer Institute) 
 
CTRP 
Clinical Trials Reporting Program 
 
DAOM 
Doctor of Acupuncture and Oriental Medicine  
 
DSMC 
Data and Safety Monitoring Committee 
 
ECOG Status 
Eastern Cooperative Oncology Group Performance Status 
 
ERICA 
Electronic Research Integrity and Compliance Administration 
 
FDA 
Food and Drug Administration  
 
fMRI 
Functional Magnetic Resonance Imaging  
 

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Principal Investigator: Taylor-Swanson 
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Abbreviation or 
Term1 
Definition/Explanation 
GB 34 
Gall Bladder 34 
 
GB 40 
Gall Bladder 40 
 
HCI 
Huntsman Cancer Institute 
 
INC 
Imaging and Neuroscience Center 
 
IND 
 
Investigational New Drug 
IRB 
Institutional Review Board 
 
KD 3 
Kidney 3 
 
LI 10 
Large Intestine 10 
 
MAIA-2 
Multidimensional Assessment of Interoceptive Awareness Version 2 
 
MRI 
Magnetic Resonance Imaging 
 
N/A 
Not applicable 
 
NCI 
National Cancer Institute 
 
 
PIs 
Primary Investigators 
 
RCO 
Research Compliance Officer  
 
SAE 
Serious Adverse Event 
 
SC 
Study Coordinator 
 
SPSS 
Statistical Package for the Social Sciences 
 
SSNRIs 
Selective Serotonin and Norepinephrine Reuptake Inhibitors 
 

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Principal Investigator: Taylor-Swanson 
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Abbreviation or 
Term1 
Definition/Explanation 
ST 36 
Stomach 36 
 
ST 41 
Stomach 41 
 
STRICTA 
Standards for Reporting of Controlled Trials in Acupuncture 
 
TNSc 
Total Neuropathy Scale Clinical version 
 
All of these abbreviations may or may not be used in protocol.  
 
 

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Principal Investigator: Taylor-Swanson 
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PROTOCOL SIGNATURE 
 
 
I confirm that I have read this protocol, and I will conduct the study as outlined herein and 
according to the ethical principles stated in the latest version of the Declaration of Helsinki, the 
applicable ICH guidelines for good clinical practice, and the applicable laws and regulations of 
the federal government.   
 
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who assist in the conduct of this study.  I will discuss this material with them to ensure that 
they are fully informed regarding the study treatment, the conduct of the study, and the 
obligations of confidentiality. 
 
 
____________________________________ 
12/3/2019 
Signature of Principal Investigator  
 
Date 
 
 
 
Lisa Jean Taylor-Swanson PhD, MAcOM, LAc  
Principal Investigator Name  
 
 
 
College of Nursing, University of Utah  
Name of Institution 

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Principal Investigator: Taylor-Swanson 
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STUDY SUMMARY 
 
Title 
Acupuncture Treatment of Chemotherapy-
Induced Peripheral Neuropathy (CIPN) in 
Women with Breast or Gynecologic 
Cancers: Feasibility and Mechanisms of 
Action 
Short Title 
CIPN Acu 
Protocol Number 
N/A 
Phase 
Clinical study phase: pilot phase II study 
Design 
Single arm, pilot feasibility study  
Study Duration 
18 months 
Study Center(s) 
Single-center: HCI/HCH 
Objectives 
This pilot study aims to demonstrate 
feasibility to recruit, retain and provide the 
study intervention and to identify potential 
mechanisms of action of acupuncture in 
CIPN management.  
Number of Subjects 
N=20 
Diagnosis and Main Eligibility Criteria 
This study will enroll female patients who 
have completed paclitaxel or docetaxel 
treatment at least 3 months prior with at 
least one month of altered sensation in feet 
(with or without presence in one or both 
hands) and/or pain with a score of greater 
than or equal to 20 for CIPN on the 
sensory subscale of the CIPN-20. 
Enrollment will be limited to patients with 
breast, ovarian, cervical, endometrial, or 
uterine cancer with CIPN and completed 
paclitaxel or docetaxel treatments.   
Statistical Methodology 
Primary Endpoints: Mean monthly 
enrollment, percentage completion rate of 
all study procedures, frequency count of 
serious adverse events, and percentage of 
enrolled participants completing 
questionnaires will be calculated. Data 
will be collected via REDCap and 
analyzed with SPSS.  
 
Analysis of demographic data will consist 
of calculating means, standard deviations, 
frequencies, and proportions. Analysis of 
feasibility data will consist of calculating 
frequencies and percentages. Analysis of 
questionnaires will consist of within-

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group pre/post analysis with student t-test 
and chi square with significance will be 
set at .05 and two-tailed hypotheses.  
 
Sample Size Estimation: A sample size 
of 25-30 participants is ideal for a pilot 
feasibility study1. However, we are 
recruiting only 20 participants due to 
funding constraints.  
 
1 OBJECTIVES 
This pilot study aims to evaluate the feasibility to conduct a study of acupuncture treatment (AT) 
for Chemotherapy-Induced Peripheral Neuropathy (CIPN) at Huntsman Cancer Institute and to 
investigate changes in physiological biomarkers when using acupuncture to treat CIPN.  
1.1 Primary Objectives and Endpoints 
To evaluate the feasibility to conduct a trial of AT for CIPN + standard of care therapy. 
Primary feasibility objectives will be evaluated in terms of recruitment (enrollment of 20 
women, average of 2 eligible women per month to participate in the trial, identification of 
appropriate recruitment strategies, the appropriateness of eligibility criteria), retention (70% 
or more participants comply with 8 or more AT sessions and complete both fMRI scans), 
safety (zero serious adverse events directly related to AT) and questionnaire completion 
(70% or more enrolled participants comply with all data collection).  
1.1.1 Primary outcome measures: Mean enrollment, completion rate of AT, fMRI, rate 
of serious adverse events, rate of questionnaire completion. 
1.2 Secondary Objectives and Endpoints 
To evaluate the impact of AT on the reported experience of CIPN. 
1.2.1 To evaluate central pain processing and cortical connectivity in patients with 
CIPN treated by acupuncture by analyzing fMRI of all participants.  
1.2.2  To evaluate if there is any change in patient-reported measures from before AT to 
after study completion.  
2 BACKGROUND 
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and disabling 
complications of cancer chemotherapy. CIPN is a major cause of morbidity and reduced quality 
of life among cancer survivors due to pain, gait instability, and fall related injury. Up to 60% of 
patients receiving potentially neurotoxic chemotherapeutics develop CIPN, 40% of whom have 
persistent neuropathy after termination of chemotherapy.2,3 CIPN commonly necessitates dose 
reduction or cessation of therapy, potentially limiting treatment efficacy and likely impacting 
patient outcomes.4 First-line treatments include anticonvulsants, tricyclic antidepressants, 
selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) and topical lidocaine.5 

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Second-line treatments include opioids. Given the risk of abuse, overdose and addiction, 
treatments besides opioids are advised and warrant investigation. A multimodal approach may be 
most effective, with acupuncture being a safe option reporting low rates of adverse events6. 
Acupuncture treatment (AT) is a well-tolerated and safe treatment option frequently used for 
symptoms associated with cancer therapies such as nausea, vomiting, xerostomia and fatigue.7  
Several case series and small uncontrolled trials of AT for CIPN suggest potential efficacy, 
although well-designed and powered clinical trials are lacking and mechanisms underlying AT’s 
potential efficacy are unknown.8-14 
 
Although drug-induced damage to the peripheral nervous system is well recognized in CIPN, the 
central nervous system (CNS) also shows concomitant involvement. Much of our current 
understanding of the pathophysiology of central pain processing in chronic painful conditions 
such as diabetic neuropathy, trigeminal neuralgia, post-herpetic neuralgia and chronic low back 
pain has utilized functional magnetic resonance imaging (fMRI). Previous pain-related 
functional studies identified alterations in brain activation in multiple cortical and subcortical 
regions including the frontal lobe, insular cortex, somatosensory cortex, thalamus, periaqueductal 
grey and precuneus.15  
 
While fMRI has not yet been used to evaluate mechanisms of action of AT in the context of 
CIPN, an increasing number of studies have applied fMRI to investigate AT over a wide range of 
pain disorders. Stimulation of acupuncture points is associated with overlapping activity in 
cortical and subcortical brain regions, including the insula, thalamus, anterior cingulate cortex, 
primary and secondary somatosensory cortices, and deactivation in limbic-paralimbic-
neocortical network. Acupuncture can modulate activity within specific brain areas, many of 
which are known to be important to CIPN pain processing. We hypothesize that regions involved 
in pain perception will show decreased connectivity between the insula, amygdala and 
somatosensory cortex with successful pain treatment, with decreased task-related activation of 
the brain’s salience network (anterior cingulate and frontal insula) during mental pain 
imagery. 13-15   
 
Additionally, neurological evidence indicates that some of the brain regions activated during 
pain perception are also activated when engaging in interoceptive awareness. 16 Acupuncture has 
been shown to alter pain processing regions but has not been evaluated regarding changes in 
mind-body awareness.  The possible role of enhanced mind-body awareness as a mechanism of 
action of acupuncture has not yet been tested. This pilot study will provide a preliminary fMRI 
and questionnaire data for this topic. Clinical trials of interventions such as mindfulness-based 
cognitive therapy demonstrate increased interoceptive awareness17 and decreased depression18. It 
seems plausible that AT may provide an opportunity for participants to increase their mind-body 
awareness while they lie on the treatment table and relax, as well as via neurologic changes in 
the insula, amygdala, and somatosensory cortex. These regions are known to affect pain 
processing as well as interoceptive (or mind-body) awareness. 
 
This pilot feasibility study aims to determine if conducting a trial of AT for CIPN is feasible 
at HCI. We aim to enroll and retain twenty participants who will undergo fMRI during the 
baseline visit, receive up to 10 sessions of AT, and undergo fMRI after completion of AT. We 
will examine fMRI for potential neurologic mechanisms of action of AT in CIPN management. 

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The ultimate objective of this pilot project is to lay the foundation for a future randomized 
controlled clinical trial of AT for CIPN. Specifically, we will be able to demonstrate that we 
have the team and location in place to conduct a successful trial.  
 
3 DRUG INFORMATION 
 
N/A 
4 STUDY DESIGN 
4.1 Description 
We propose a pilot feasibility trial. Oncologists at Huntsman Cancer Institute (HCI) will be 
informed of the trial and asked to refer female patients diagnosed with breast or gynecologic 
cancer and CIPN who have completed all paclitaxel or docetaxel treatments three or more 
months previously. All referred patients will be informed of the study and voluntarily recruited 
by the Study Coordinator (SC). The SC will call the individual after sending a recruitment letter, 
inform them of the study, screen them for eligibility, and if consent is obtained, enroll the 
participant. Standard oncological care is defined as care the participant was already receiving and 
that care will not be interrupted in any way for any study participant.  
 
4.2 Dose Limiting Toxicity  
N/A 
4.3 Number of Patients 
Twenty participants will be enrolled. Sample size for this pilot feasibility study is determined by 
budgetary constraints. While a sample of 25-30 would be ideal for the aims of this study1, we are 
limited by our study budget to twenty participants.  
 
4.4 Number of Study Centers 
All participants will be recruited from HCI and AT will be delivered onsite at HCI in the Linda 
B. and Robert B. Wiggins Wellness and Integrative Health Center. This is a single-center pilot 
phase II trial. 
4.5 Study Duration  
Eighteen months. 
5 ELIGIBILITY CRITERIA 
 
This eligibility checklist is used to determine patient eligibility and filed with signature in the 
patient research chart.  
  
Patient No. ______________________ 
Patient’s Initials: (L,F,M) _________________ 

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5.1 Inclusion Criteria 
Yes/No  (Response of “no” = patient ineligible) 
5.1.1 _____ Female age 18 or older. 
5.1.2 _____ Histologically proven breast, uterine, cervical or ovarian cancer of any 
stage. 
5.1.3 _____ Received either (1) a Paclitaxel treatment dose of at least 480 mg/m2 
paclitaxel as a single or combination agent or (2) a Docetaxel treatment dose of at 
least 150 mg/m2 docetaxel as a single or combination agent. Treatment must be 
completed at least 3 months prior to enrollment. 
5.1.4 _____ Eligible patients report at least 1 month of altered sensation and/or pain in 
the feet (with or without presence in one or both hands) with a score of greater 
than or equal to 20 for CIPN on the sensory subscale of the CIPN-20 (scale 0-
100).  
5.1.5. _____ Able to provide informed consent and willing to sign an approved consent 
form that conforms to federal and institutional guidelines.   
5.1.6. _____ ECOG status of 0 (asymptomatic), 1 (symptomatic but completely 
ambulatory) or 2 (symptomatic, <50% in bed during the day).  
 
5.2 Exclusion Criteria 
Yes/No (Response of “yes” = patient ineligible) 
5.2.1 _____ Preexisting neuropathy due to other identified etiologies includes diabetes, 
vitamin B12 deficiency, or alcoholism. 
5.2.2 _____ Having received more than 6 acupuncture treatments for any condition in 
the last six months. 
5.2.3 _____ Patients with claustrophobia, pacemakers, non-MRI compatible breast 
expanders or port-a-caths, neurostimulator devices, current or expected 
pregnancy, exposure to shrapnel, left-handedness, recent tattoos or otherwise 
unsafe for MRI scanning.  
 
I certify that this patient meets all inclusion and exclusion criteria for enrollment onto this 
study.  
 
______________________________ 
 
_________ 
 
Investigator Signature  
 
 
 
Date  
 
 

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6 STRATIFICATION FACTORS 
N/A 
7 TREATMENT PLAN 
7.1 Administration Schedule 
Twenty participants will be enrolled. The manualized acupuncture treatment (AT) intervention 
will be designed by Dr. Budhathoki and Dr. Taylor-Swanson and administered by Dr. 
Budhathoki and members of Huntsman acupuncture team. Ten sessions of AT will be delivered: 
twice per week for 2 weeks, thereafter once per week for six weeks, with a total of 10 treatments 
during a two-month course. Each session will last 45-60 minutes, with acupuncture needles 
retained 30-40 minutes. A minimum of 8 treatments must be received within the acupuncture 
treatment window. Concurrent medications are allowed as prescribed and will be tracked in the 
study and analyzed as potential confounders.  
 
Participants in the study will undergo study interview and fMRI at the following two time points: 
within 9 days after baseline following enrollment and within one week of acupuncture treatment 
completion. Clinical data including current medications and medical history and fall rates will be 
gathered during the baseline and study conclusion. Questionnaires will be completed in person or 
emailed to patients via REDCap at baseline and study conclusion, as well as at a 3-month follow-
up.  Reminder calls and AT appointments will be scheduled by HCI Wellness and Integrative 
Health Center personnel in coordination with the study coordinator (SC). The SC will aid 
participants in scheduling fMRI with an online scheduling system. 
 
 
7.2 Acupuncture treatment and ongoing standard care Treatment 
7.2.1 How Supplied, Stored, Packaged and Labeled 
Acupuncture needles arrive labeled, sealed and boxed from the manufacturer and are 
stored in a secured cabinet. All acupuncture needles remain unopened until use.  
7.2.2 Preparation and Administration 
Acupuncture will be provided according to standard procedure and will include use of 
Clean Needle Technique. 
 
Clean Needle Technique 
In the United States, Clean Needle Technique (CNT) is governed by the CCAOM, the 
Council of Colleges of Acupuncture and Oriental Medicine.  This study will follow the 
CNT outlined by the CCAOM, 6th ed. (2009) 
CNT helps to ensure participant and practitioner safety in the acupuncture process  
 
General CNT Guidelines 
Clean needle technique requires the following: 
Hand washing before and after patient contact, and before setting up a clean field 
Set up a clean field with equipment and supplies 
Locate the acupuncture point 

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Uni-directional swabbing of the acupuncture point with alcohol 
Needling with guide tube and adjust needle to desired depth 
At end of session, remove and immediately isolate acupuncture needles into approved 
sharps containers 
 
Acupuncture Needles  
Acupuncture needles are regulated as medical devices by the United States Food and 
Drug Administration.  The acupuncture needles to be used in this clinical trial will be 
single-use, sterile acupuncture needles.  
 
Acupuncture Needles: DBC™ Spring Ten needle .16 x 30mm, 40-gauge (manufactured 
by DBC Made in Korea; distributed by Lhasa OMS, Inc. Weymouth, MA)  
Auricular Acupuncture Needles: DBC™ Sooji Chim Korean Hand Needles .18x30mm, 
42-gauge DBC needles (manufactured by DBC Made in Korea; distributed by Lhasa 
OMS, Inc. Weymouth, MA) 
Scalp Acupuncture Needles: Nano Tech™.16 x 30mm, 40-gauge (manufactured by DBC 
Made in Korea; distributed by Lhasa OMS, Inc. Weymouth, MA) 
 
Note: if these specific needles are unavailable for use, whichever brand is used clinically 
by the staff will also be used for study participants.  
 
The acupuncture protocol and procedures employed have been devised with adherence to 
the Standards for Reporting of Controlled Trials in Acupuncture (STRICTA) 
recommendations.  The point prescription in this study is a manualized protocol (i.e., a 
protocol that is standardized but allows the Study Acupuncturist to modify treatments 
based on the patient’s current symptoms).   
 
Manualized Protocol 
A manualized protocol was chosen, as opposed to a fixed acupuncture point protocol, in 
order to facilitate a standardization of treatments and because it was shown to be effective 
in a number of other acupuncture clinical trials. Acupuncture points relevant to an 
individual patient will be selected from the list below. 
 
ACUPUNCTURE POINTS ALLOWED IN THE MANUALIZED PROTOCOL 
 
Point 
Name 
Location – from Chinese Acupuncture and Moxibustion, Foreign Languages 
Press, Beijing (2010, Xinnong, C., 3rd ed.) 
Full body acupuncture points (given at each visit, bilaterally) 
LI 10 
On the line joining Yangxi (LI-5) and Quchi (LI-11), 2 cun below the cubital 
crease. 
GB 
40 
Anterior and inferior to the external malleolus, in the depression on the lateral 
side of the tendon of m. extensor digitorum longus. 
GB 
34 
 
In the depression anterior and inferior to the head of the fibula. 

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ST 
41 
On the dorsum of the foot, at the midpoint of the transverse crease of the ankle 
joint, in the depression between the tendons of m. extensor digitorum longus and 
hallucis longus, approximately at the level of the tip of the external malleolus. 
ST 
36 
3 cun below Dubi (ST-35), one finger-breadth (middle finger) from the anterior 
border of the tibia. 
KD 3 
In the depression between the tip of the external malleolus and the anterior side 
of the tendon Achilles. 
Ba 
Xie 
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. 
Ba 
Feng 
On the dorsum of the foot, between the toes, 0.5 cun proximal to the margin of 
the web. 
Auricular acupuncture points: Shen Men, Thalamus, Endocrine, Point Zero, Sympathetic 
 
 
 
Standard care will be delivered according to the participants’ healthcare team. 
7.2.3 Accountability and Compliance 
The Licensed Acupuncturists in this study are licensed in the state of Utah under the Utah 
Code Title 58 Chapter 72 Acupuncture Licensing Act.  Licensed Acupuncturists are also 
credentialed through the University of Utah medical credentialing department as advance 
practice clinicians to provide acupuncture treatments in the Huntsman Cancer Hospital 
and throughout University of Utah healthcare system.   
 
The Licensed Acupuncturists in this study comply with all state and federal regulations 
for acupuncture and the scope of practice set forth at the Huntsman Cancer Hospital 
and University of Utah.  
7.3 Prohibited Concomitant Medications 
No concomitant medications are prohibited in this study. 

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7.4 Duration of Therapy 
Ten sessions of AT will be delivered: twice per week for 2 weeks, thereafter once per week for 
six weeks, with a total of 10 treatments during a two-month course. Each session will last 45-60 
minutes, with acupuncture needles retained 30-40 minutes. A minimum of 8 treatments must be 
received by each participant with no more than 10 days’ gap between treatments permitted. 
Participants who do not complete 8 or more acupuncture sessions will be dropped from the 
study. All participants will be educated as to the importance of completion of the study after 
baseline.  
 
Subjects must be withdrawn from the study treatment for the following reasons:  
 
•    Subject withdraws consent from the study treatment and/or study procedures.  A subject 
must be removed from the trial at his/her own request or at the request of his/her legally 
acceptable representative.  At any time during the trial and without giving reasons, a 
subject may decline to participate further.  The subject will not suffer any disadvantage 
as a result. 
•    Subject is lost to follow-up. 
•    Death. 
 
Subjects may be withdrawn from the study for the following reasons:  
• The subject is non-compliant with trial procedures. 
• If, in the investigator's opinion, continuation of the trial would be harmful to the 
subject's well-being. 
• The development of an additional cancer.  
• Development of an intercurrent illness or situation which would, in the judgment of 
the investigator, significantly affect assessments of clinical status and trial endpoints. 
•  Deterioration of ECOG performance status to 4. 
 
8 TOXICITIES AND DOSEAGE MODIFICATION 
N/A 
 
This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) 
Version 5.0 for adverse event and serious adverse event reporting.   
8.1 Dose Modifications 
 
   N/A 
8.2 Supportive Care 
8.2.1 All supportive measures consistent with optimal patient care will be given 
throughout the study. 
 

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9 STUDY CALENDAR 
 
 
 
 
 
Week (+/- 2 days) 
 
Week (+/- 7 
days) 
Examination 
Screenin
g1 
Baseline1,
2 
Day 1 
1 2 3 4 5 6 7 8 9 
End of 
study5 
22 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medications 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
Questionnaires3 
 
 
 
 
 
 
 
 
 
 
 
 
 
• CIPN-20 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
• BPI 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
• CIPN-R-ODS 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
• MAIA-2 
 
X 
 
 
 
 
 
 
 
 
 
X 
X 
• Demographics 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Acupuncture treatment 
(AT)4 
 
 
 
X
X 
X
X 
X X X X X X 
 
 
 
fMRI6 
 
 
X  
 
 
 
 
 
 
 
X 
 
 
1 Screening visit and Baseline visit can occur on the same day.  
2 Day 1 (Baseline) should occur within 2 weeks of the screening visit. 
3 Questionnaires include: (See Appendices). 
4 Acupuncture treatment (AT) will occur at the Wellness & Integrative Health Center at HCI. 
Twice a week treatments will occur within 4 business days.  
5 End of study visit should occur within one week of final acupuncture treatment.  
6 Must be within 9 days of baseline visit. If participant prefers, first study fMRI can be same day 
as first AT treatment.  
 
10 STUDY PROCEDURES 
This study will enroll female patients who have completed treatment with either 
paclitaxel or docetaxel at least three months prior. Paclitaxel is a neurotoxic chemotherapy 
known to cause CIPN. Docetaxel is also a neurotoxic chemotherapy known to cause CIPN.  
Patients must have experienced at least one month of altered sensation in feet (with or without 

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presence in one or both hands) and/or pain with a score of greater than or equal to 20 for CIPN 
on the sensory subscale of the CIPN-20. We will commence recruitment 3 months after patients 
have completed their last chemotherapy dose. 
Patients will be recruited from the Huntsman Cancer Center Oncology Clinics in 
collaboration with their oncologists.  
For this study, enrollment will be limited to patients with breast, ovarian, cervical, 
endometrial, or uterine cancer with CIPN and completed chemotherapy treatments.   
 
Visits:  
Screening Visit: 
Potentially eligible subjects will be scheduled for a screening visit.  After informed consent is 
obtained, the SC will review and confirm inclusion/exclusion criteria. The SC will take a brief 
medical, history and administer the CIPN-20 questionnaire. If all inclusion and exclusion criteria 
are fulfilled, the subject will be scheduled for a baseline visit. This visit may occur on the same 
day as screening, but must occur within 2 weeks of study screening visit. If the participant has 
received treatment outside of University of Utah Health a medical record release form will be 
initiated and submitted as appropriate.  
 
Baseline Visit: 
Patients diagnosed with breast, ovarian, cervical, endometrial, or uterine cancer who will be 
treated with paclitaxel or docetaxel chemotherapy associated with CIPN will undergo a number 
of questionnaires. The patient will then be enrolled in the study and scheduled in the Wellness 
Center for acupuncture therapy (AT). All participants will be scheduled for fMRI , which must 
occur within nine days after baseline.  
Participants will undergo study interview and fMRI within 9 days after baseline 
following enrollment.  
Clinical data including current medications and medical history and fall rates will be 
gathered. Questionnaires (BPI, CIPN-20, CIPN-R-ODS, MAIA-2, Demograhpics) will be 
completed in person or emailed to patients via REDCap. Reminder calls and AT appointments 
will be scheduled by HCI Wellness and Integrative Health Center personnel in conjunction with 
a SC. The SC will aid participants in scheduling fMRI appointments online. AT treatments will 
occur within 7 days/4 business days in general. If participant prefers the first study fMRI and 
first AT appointment can occur same day, with the fMRI procedure occurring prior to AT 
treatment.  
 
Follow up Visits:   
Participants will receive 10 sessions of AT: twice per week for 2 weeks, thereafter once per week 
for six weeks, with a total of 10 treatments during a two-month course. Each session will last 45-
60 minutes, with acupuncture needles retained 30-40 minutes. A minimum of 8 treatments must 
be received by each participant with no more than 9 days’ gap between weekly  
treatments permitted (sessions 5-10). Concurrent medications are allowed as prescribed and will 
be tracked in the study and analyzed as potential confounders.   
 
Final Visit:  
Participants will undergo examination within one week of AT completion. This will include the 
fMRI scan and questionnaires.  Compensation for participation will be offered at this visit.  

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Procedures: 
 
Measures: Questionnaires will be completed in person or emailed to patients via REDCap at 
baseline and study conclusion, as well as at a 3-month follow-up. Primary Endpoints: Mean 
enrollment, percentage completion rate of all study procedures, frequency count of serious 
adverse events, and percentage of enrolled participants completing questionnaires will be 
calculated. Data will be collected via REDCap, stored in the Research Subject Registry (RSR) 
and analyzed with SPSS.  
 
Additional measures to be collected: CIPN-20: This measure includes questions about tingling, 
numbness, painful numbness, cramps, balance, temperature intolerance, grasping items, ankle 
flexion weakness and leg weakness. CIPN-R-ODS (a validated measure of quality of life specific 
to CIPN), will be used to assess impact on function, BPI to assess pain and Multidimensional 
Assessment of Interoceptive Awareness (MAIA-2) to assess mind-body awareness. We will also 
collect demographic information including age, marital status, race and ethnicity. Related 
medical history and current medications information will be collected.  
 
Acupuncture therapy (AT): AT will be delivered onsite at HCI in the Linda B. and Robert B. 
Wiggins Wellness & Integrative Health Center. AT will be delivered twice per week 
for two weeks and then weekly for six weeks by Annie Budhathoki, DAOM, a Licensed 
Acupuncturist who has over five years’ clinical experience treating persons with cancer, or 
another Licensed Acupuncturist in the Wellness & Integrative Health Center. Each session will 
last 45-60 minutes, with acupuncture needles retained 30-40 minutes. A minimum of 8 
treatments must be received by each participant. 
 
Functional MRI (fMRI) to be conducted within 9 days after baseline and within 1 week of final 
AT session. fMRI scans will be conducted at Imaging and Neuroscience Center (INC) in 
Research Park. Imaging will consist of structural brain imaging (MP2RAGE), task fMRI, and 
resting-state fMRI connectivity. Task fMRI will consist of a mental imagery task with a 20-
second block design wherein patients will alternate between concentration on a part of their body 
where they experience pain and a part of their body where they do not experience pain, prompted 
by visual cues.  We will provide gift cards for $25 after the completion of the second fMRI. 
 
11 CRITERIA FOR EVALUATION AND ENDPOINT 
 
11.1 Feasibility  
To evaluate the feasibility to conduct a trial of AT for CIPN + standard of care therapy. 
Primary feasibility objectives will be evaluated in terms of recruitment (enrollment of 20, 
average of 2 eligible women per month to participate in the trial, identification of appropriate 

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recruitment strategies, the appropriateness of eligibility criteria), retention (70% or more 
participants comply with AT attendance defined as 8 or more of 10 AT sessions, and 
complete both fMRI scans), safety (zero serious adverse events directly related to AT) and 
questionnaire completion (70% or more enrolled participants comply with data collection).  
Primary outcome measures: Mean enrollment, completion rate of AT and fMRI, rate of 
serious adverse events, rate of questionnaire completion. 
 
11.2 Safety 
 
The DSMC will consist of the appropriate Huntsman Cancer Institute (HCI) DSMC members.  
Overall safety of this study will be assessed using the CTCAE (NCI Common Terminology 
Criteria for Adverse Events) version 5.0 and the following safety and tolerability endpoints will 
be used: 
-incidence of treatment-emergent adverse events associated (TEAE's) with acupuncture- known 
TEAE's detailed below. 
Patients will be instructed to disclose all study-related side-effects, symptoms or AEs. 
Potential adverse effects of acupuncture treatment include:  
Bruising  
Bleeding  
 
Needle shock 
Pre-syncope (Dizziness) 
Diaphoresis (Sweating) 
Nausea and Vomiting 
Loss of consciousness 
 
The main side effects of acupuncture include a slightly increased risk of minor bruising and 
bleeding and rarely infection. Needle shock, a vaso-vagal response to needle insertion, occurs 
about 5% of the time usually during the first or second treatment.  Patients may become faint, 
diaphoretic, nauseated and occasionally lose consciousness. These are often reversible by 
removing the acupuncture needles and laying the patient supine. 
-incidence of procedure-related adverse events associated with fMRI (source: FDA) 
MR images are made without using any ionizing radiation, so patients are not exposed to the 
harmful effects of ionizing radiation. But while there are no known health hazards from 
temporary exposure to the MR environment, the MR environment involves a strong, static 
magnetic field, a magnetic field that changes with time (pulsed gradient field), and 
radiofrequency energy, each of which carry specific safety concerns: 
• 
The strong, static magnetic field will attract magnetic objects (from small items such as keys 
and cell phones, to large, heavy items such as oxygen tanks and floor buffers) and may cause 
damage to the scanner or injury to the patient or medical professionals if those objects 

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become projectiles. Careful screening of people and objects entering the MR environment is 
critical to ensure nothing enters the magnet area that may become a projectile. 
• 
The magnetic fields that change with time create loud knocking noises which may harm 
hearing if adequate ear protection is not used. They may also cause peripheral muscle or 
nerve stimulation that may feel like a twitching sensation. 
• 
The radiofrequency energy used during the MRI scan could lead to heating of the body. The 
potential for heating is greater during long MRI examinations. 
Acupuncture Schedule Adjustments 
The main toxic effects of acupuncture include a slightly increased risk of minor bruising and 
bleeding and rarely infection. Needle shock, a vaso-vagal response to needle insertion, occurs 
about 5% of the time usually during the first or second treatment. Patients may become pre-
syncopal, diaphoretic, nauseated and occasionally lose consciousness. These symptoms are 
easily reversible by removing the acupuncture needles and laying the patient supine. There are 
no universal guidelines in patients with lymphoedema however there may be hospital, academic 
medical center, or department specific guidelines. These concerns can adequately be addressed 
by the Study Acupuncturist as toxic effects of acupuncture are taught in all acupuncture schools. 
Reporting adverse events and referrals for patient care 
During the study, all study patients will be under the care of either a medical oncologist or a 
surgical oncologist. If any abnormalities or problems, including possible study related adverse 
events (AE) or reportable serious adverse events(SAEs), are detected during screening, 
subsequent measurements, or study activities, the patient will be referred back to their medical 
provider for appropriate care. The SC and study primary investigators (PIs) will be responsible 
for recording and reporting any intervention related AEs and reportable SAEs.  The possible 
routes of referral are as follows: 
a. Abnormality/problem detected during screening and subsequent clinic visits: The SC will 
notify and discuss with the study PIs. The responsible site investigator as appropriate will refer 
the patient to their medical provider. The SC and study PIs will record and report any study-
related AEs and reportable SAEs as appropriate. 
b. Abnormality/problem detected during telephone contact: The SC will refer the patient to their 
medical provider and the responsible site investigator as appropriate. The SC and study PIs will 
record and report AEs and reportable SAEs as appropriate. 
c. Abnormality/problem detected during acupuncture session: The Study Acupuncturist will 
notify and discuss with the responsible site investigator. The SC will be notified and the SC and 
the responsible site investigator as appropriate will refer the patient to their medical provider. 
The SC and study investigators will record and report as appropriate. 
More on adverse event procedures are outlined in section 16.4.1 

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11.3 Stopping Rules 
Conditions that may lead to reasonable cause and warrant termination of this study include, but 
are not limited to:  
-Subject or investigator noncompliance 
-Unsatisfactory subject enrollment 
-Lack of adherence to protocol procedures 
-Lack of valuable and/or complete data 
-Potentially unacceptable risk to study subjects 
12 STATISTICAL CONSIDERATIONS 
Data will be collected via REDCap and analyzed with SPSS. Missing data will be handled with 
imputation of the median value of all available data for each individual item.19 
 
Demographics: Analysis of demographic data will consist of calculating means, standard 
deviations, frequencies, and proportions. Demographic information to include: age, marital 
status, race and ethnicity, current medications and medical history.  
 
 
Feasibility data: will be analyzed by calculating frequency and percentages, specifically: 
• Recruitment – frequency count (enrollment of 20 women, average of 2 eligible women 
per month to participate in the trial, identification of appropriate recruitment strategies, 
the appropriateness of eligibility criteria),  
• Retention – frequency and percentage (70% or more participants comply with 8 or more 
AT sessions and complete both fMRI scans) 
• Safety – frequency count (zero serious adverse events directly related to AT)  
• Questionnaire completion – frequency and percentage (70% or more enrolled 
participants complete at least 80% of questions at all protocol-directed time points). 
 
Questionnaires: analyses will consist of student t-test and chi square computations according to 
the type of data.  
 
• CIPN-20  
• CIPN-R-ODS  
• BPI 
• Multidimensional Assessment of Interoceptive Awareness (MAIA-2) 
 
Functional MRI quantification: Volume and Surface preprocessing pipelines from the Human 
Connectome Project will be executed for each resting sequence on completion of structural 
preprocessing. MultiEcho ICA Cleaning: All resting state data will additionally be processed 
using MultiEcho ICA pipeline (AFNI) allowing removal of non-neural components in the BOLD 
data. Head motion: Rigorous control of head motion begins before acquisition with subject 

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training and instruction, continues during scanning with repeated reminders to hold still and 
analysis of image quality after each scan with repetition as possible, and postprocessing 
including voxelwise despiking, motion parameter estimation and correction, physiologic 
waveform regression, Multiecho ICA cleaning, and volume censoring (scrubbing). Post-hoc 
mean and maximal root-mean-square head motion estimates will be used as covariates for all 
biomarkers. Connectivity: Time series will be estimated FreeSurfer-defined subject-specific 
regions of interest in somatosensory cortex, anterior cingulate, anterior insula, amygdala, 
thalamus, medial prefrontal cortex, orbitofrontal cortex, and precuneus, as well as at 361 ROIs 
for graph-theoretic and network analyses (modularity and clustering coefficient) comprising 333 
cortical ROIs strategically positioned at network hubs, 14 cerebellar ROIs, and 14 subcortical 
gray matter ROIs defined from Freesurfer segmented subject specific nuclei. 
 
Functional MRI Analysis: We will analyze functional connectivity using a parcellation covering 
the cortical and subcortical gray matter at 5 mm resolution.  Brain parcellation will be 
constructed by assessing regions of interest (ROIs) and measuring each voxel, which can 
represent a million brain cells. Each voxel will be tested in sequence beginning with the inferior 
left voxel in the cerebellum. If a voxel is greater than 5 mm distant to voxels already selected, 
then this voxel will be included in the set of ROI center coordinates.  
13 REGISTRATION GUIDELINES 
N/A 
 
Patients must meet all of the eligibility requirements listed in Section 5 prior to study 
procedures.   
 
14 DATA SUBMISSION SCHEDULE 
       N/A 
15 SPECIAL INSTRUCTIONS  
15.1 Pathology review 
N/A 
15.2 Pharmacokinetic 
N/A 
15.3 Correlative Studies 
N/A 
16 ETHICAL AND REGULATORY CONSIDERATIONS 
16.1 Informed consent  
Informed consent will be obtained from all research participants prior to performing any 
study procedures using the most recent Institutional Review Board (IRB) approved version.  

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16.2 Institutional Review 
Study will be approved by the IRB of University of Utah. 
16.3  Data and Safety Monitoring Plan 
A Data and Safety Monitoring Committee (DSMC) is established at Huntsman Cancer 
Institute (HCI) and approved by the NCI to assure the well-being of patients enrolled on 
Investigator Initiated Trials that do not have an outside monitoring review.  Roles and 
responsibilities of the DSMC are set forth in the NCI approved plan.  The activities of this 
committee include a quarterly review of adverse events including SAEs, important medical 
events, significant revisions or amendments to the protocol, and approval of cohort/dose 
escalations.  If the DSMC and/or the PI have concerns about unexpected safety issues, the 
study will be stopped and will not be resumed until the issues are resolved. The DSMC also 
reviews and approves audit reports generated by the Research Compliance Office.  
 
 
This study is a low risk trial.  All low risk studies are audited no less than annually by the 
Research Compliance Office and audit reports will be reviewed and approved by the full 
DSMC.  The DSMC will also review all reportable Serious Adverse Events for patients on 
this study. 
16.4 Adverse Events / Serious Adverse Events 
This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) 
Version 5.0 for AE and SAE reporting.  An electronic copy can be downloaded from:  
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_
Quick_Reference_8.5x11.pdf 
 
16.4.1 Adverse Events (AE) 
There is no protocol-directed administration of systemic therapy in this non-
pharmacologic study; patients will be taking standard of care anti-cancer therapy 
prescribed by their treating oncologist. The study-specific AE reporting plan detailed 
below will be followed. The PI will determine the attribution/relatedness of each AE. 
Any AEs with a causal relation to the research will be graded for severity and 
seriousness, and followed to either resolution or until the 3-month post follow-up 
(whichever comes first).  
 
Subjects will receive a systemic treatment regimen for their cancer during study 
participation. Since such routine interventions and treatment may influence the study 
results, information regarding the concomitant medications will be collected but not 
reported to the IRB. 
 
Potential AEs of acupuncture treatment include:  
 Excessive and/or unusual bruising 
 Excessive and/or unusual bleeding   
 Needle shock 
 Pre-syncope (Dizziness) 
 Diaphoresis (Sweating) 
 Nausea and Vomiting 

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 Loss of consciousness 
 
 
16.4.2 Serious Adverse Event (SAE) 
AE’s which are determined by the PI to be both attributable to study intervention and 
serious will be reported to the DSMC and/or the IRB as appropriate (refer to section 16.5 
for reporting requirements). An AE is considered serious when it results in one or more of 
the following: 
 Death 
 Initial or prolonged hospitalization 
 Life threatening event 
 Disability or permanent damage 
 Congenital Anomaly/Birth defect 
 Other important medical event which is deemed serious by the PI 
 
16.5 SAE Reporting Requirements 
SAEs must be reported to the DSMC and/or the IRB according to the requirements described 
below: 
 
 
DSMC Notifications: 
• All SAEs which are attributable to study intervention will be reported to the DSMC.  
• A 
MedWatch 
3500A 
form* 
must 
be 
completed 
and 
submitted 
to 
compliance@hci.utah.edu as soon as possible, but no later than 24 hours from first 
knowledge.  
• An HCI Research Compliance Officer (RCO) will process and submit the MedWatch 
form to the proper DSMC member as necessary for each individual study.  
• The RCO will summarize and present all reported SAEs according to the Data and 
Safety Monitoring Plan at the quarterly DSMC meeting. 
 
IRB Notification: 
• Events 
meeting 
the 
University 
of 
Utah 
IRB 
reporting 
requirements 
(http://www.research.utah.edu/irb/) will be submitted through the IRB’s electronic 
reporting system within 10 working days. 
 
 
*Medwatch 3500A form can be found at 
http://www.fda.gov/downloads/Safety/MedWatch/HowToReport/DownloadForms/ucm0827
28.pdf 
16.6 Reporting of Pregnancy  
Although pregnancy is not considered an adverse event, it is the responsibility of 
investigators or their designees to report any pregnancy or lactation in a subject as an SAE. 
Pregnancies or lactation that occurs during the course of the trial or with 30 days of 
completing the trial or starting another new anticancer therapy, whichever is earlier, must be 

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reported to the DSMC, and IRB. All subjects and female partners who become pregnant must 
be followed to the completion/termination of the pregnancy. Pregnancy outcomes of 
spontaneous abortion, missed abortion, fetal death, intrauterine death, miscarriage and 
stillbirth must be reported as serious events.  
16.7 Protocol Amendments 
Any amendments or administrative changes in the research protocol during the period, for 
which the IRB approval has already been given, will not be initiated without submission of 
an amendment for IRB review and approval.    
 
These requirements for approval will in no way prevent any immediate action from 
being taken by the investigator in the interests of preserving the safety of all patients 
included in the trial.  
 
16.8 Protocol Deviations 
A protocol deviation (or violation) is any departure from the defined procedures and 
treatment plans as outlined in the protocol version submitted and previously approved by the 
IRB. Protocol deviations have the potential to place participants at risk and can also 
undermine the scientific integrity of the study thus jeopardizing the justification for the 
research.  Protocol deviations are unplanned and unintentional events.  
 
Because some protocol deviations pose no conceivable threat to participant safety or 
scientific integrity, reporting is left to the discretion of the PI within the context of the 
guidelines below. The IRB requires the prompt reporting of protocol deviations which are: 
• 
Exceptions to eligibility criteria. 
• 
Intended to eliminate apparent immediate hazard to a research participant or  
• 
Harmful (caused harm to participants or others, or place them at increased risk of 
harm - including physical, psychological, economic, or social harm), or  
• 
Possible serious or continued noncompliance  
16.9 FDA Annual Reporting  
This study is Investigational New Drug (IND) exempt therefore there are no annual reporting 
requirements to the FDA.   
 
16.10 Clinical Trials Data Bank  
 
The study will be registered on http://clinicaltrials.gov  
 
16.11 Record Keeping 
Investigator records shall be kept until 2 years after the investigation is discontinued . 
 
 
 

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17 BIBLIOGRAPHY 
1. 
Hogg R, Tanis E, Zimmerman D. Probability and Statistical Inference. Pearson; 
2015. 
2. 
Park SB, Goldstein D, Krishnan AV, et al. Chemotherapy-induced peripheral 
neurotoxicity: a critical analysis. CA Cancer J Clin. 2013;63(6):419-437. 
3. 
Seretny M, Currie GL, Sena ES, et al. Incidence, prevalence, and predictors of 
chemotherapy-induced peripheral neuropathy: A systematic review and meta-
analysis. Pain. 2014;155(12):2461-2470. 
4. 
Speck RM, Sammel MD, Farrar JT, et al. Impact of chemotherapy-induced 
peripheral neuropathy on treatment delivery in nonmetastatic breast cancer. J 
Oncol Pract. 2013;9(5):e234-240. 
5. 
Kim JH, Dougherty PM, Abdi S. Basic science and clinical management of 
painful and non-painful chemotherapy-related neuropathy. Gynecol Oncol. 
2015;136(3):453-459. 
6. 
Wu X, Chung VC, Hui EP, et al. Effectiveness of acupuncture and related 
therapies for palliative care of cancer: overview of systematic reviews. Sci Rep. 
2015;5:16776. 
7. 
Stone JA, Johnstone PA. Mechanisms of action for acupuncture in the oncology 
setting. Curr Treat Options Oncol. 2010;11(3-4):118-127. 
8. 
Ben-Horin I, Kahan P, Ryvo L, Inbar M, Lev-Ari S, Geva R. Acupuncture and 
Reflexology for Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer. 
Integr Cancer Ther. 2017;16(3):258-262. 
9. 
Greenlee H, Crew KD, Capodice J, et al. Randomized sham-controlled pilot trial 
of weekly electro-acupuncture for the prevention of taxane-induced peripheral 
neuropathy in women with early stage breast cancer. Breast Cancer Res Treat. 
2016;156(3):453-464. 
10. 
Han X, Wang L, Shi H, et al. Acupuncture combined with methylcobalamin for the 
treatment of chemotherapy-induced peripheral neuropathy in patients with 
multiple myeloma. BMC Cancer. 2017;17(1):40. 
11. 
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. Evid Based 
Complement Alternat Med. 2013;2013:349653. 
12. 
Schroeder S, Meyer-Hamme G, Epplee S. Acupuncture for chemotherapy-
induced peripheral neuropathy (CIPN): a pilot study using neurography. 
Acupunct Med. 2012;30(1):4-7. 
13. 
Wong R, Sagar S. Acupuncture treatment for chemotherapy-induced peripheral 
neuropathy--a case series. Acupunct Med. 2006;24(2):87-91. 
14. 
Wong R, Major P, Sagar S. Phase 2 Study of Acupuncture-Like Transcutaneous 
Nerve Stimulation for Chemotherapy-Induced Peripheral Neuropathy. Integr 
Cancer Ther. 2016;15(2):153-164. 
15. 
Boland EG, Selvarajah D, Hunter M, et al. Central pain processing in chronic 
chemotherapy-induced peripheral neuropathy: a functional magnetic resonance 
imaging study. PLoS One. 2014;9(5):e96474. 
16. 
Craig AD. Interoception: the sense of the physiological condition of the body. 
Curr Opin Neurobiol. 2003;13(4):500-505. 

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17. 
de Jong M, Lazar SW, Hug K, et al. Effects of Mindfulness-Based Cognitive 
Therapy on Body Awareness in Patients with Chronic Pain and Comorbid 
Depression. Front Psychol. 2016;7:967. 
18. 
de Jong M, Peeters F, Gard T, et al. A Randomized Controlled Pilot Study on 
Mindfulness-Based Cognitive Therapy for Unipolar Depression in Patients With 
Chronic Pain. J Clin Psychiatry. 2018;79(1). 
19. 
Walton MK. Addressing and advancing the problem of missing data. J Biopharm 
Stat. 2009;19(6):945-956. 
 
 
 

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Appendix A: CIPN-20 
 
20 Items are scored 1 to 4 with 1 representing “not at all” and 4 “very much.” Maximum score is 
100. Higher scores indicate worse CIPN.  
 
 
 
 
 

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Appendix B: CIPN-R-ODS 
 
Each item is rated on a scale of 0-5: 
 
 
 
 

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Appendix C: Brief Pain Inventory (BPI)  
 
4 Items are scored from 0 ‘no pain’ to 10 ‘pain as bad as you can imagine’ 
1 item is scored 0% ‘no relief’ to 100% ‘complete relief’ regarding how much relieve pain 
treatments or meications provided. 
7 items ar rated from 0 ‘does not interfere’ to 10 ‘completely interferes’ regarding pain 
interference.  
 
 
 

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Appendix D: Multidimensional Assessment of Interoceptive Awareness (MAIA-2) 
37 items are rated from 0 ‘never to 5 ‘always’ 

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