Role of Home-based Transcutaneous Electrical Acustimulation for Treatment of Pain in Patients With Chronic Pancreatitis- A Pilot Study
Phase: NA
Conditions: Chronic Pancreatitis
Sponsor: University of Michigan

Role of home-based transcutaneous electrical 
acustimulation for treatment of pain in patients 
with chronic pancreatitis – A Pilot study 
 
NCT06015945 
 
Date of IRB Approval: 9/26/2024 

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Title: Role of home-based transcutaneous electrical acustimulation for treatment of pain in 
patients with chronic pancreatitis – A Pilot study 
 
Trial acronym: TEA-CuP (transcutaneous electrical acustimulation in chronic pancreatitis) 
Investigators: Jorge D. Machicado MD, MPH; Matthew DiMagno, MD; Jiande Chen, PhD 
Location: Michigan Medicine, 1500 E. Medical Center Drive, Ann Arbor Mi 48019 
 
1. Background:  
Abdominal pain is the hallmark of chronic pancreatitis (CP) and ~90% of CP patients 
experience abdominal pain at some point during the disease course 1. Although medical 
management with nonopioid analgesics is the first step in the management of painful CP, this is 
often insufficient. In population-based studies, 25% are prescribed opiates, 22% require 
endoscopic procedures, and 11% undergo surgery.2, 3 However, pain in CP is debilitating and 
often refractory to interventions, resulting in low quality of life, high rates of disability, and 
increased resource utilization.4 Therefore, novel methods to reduce pain in CP are needed.  
Acupuncture is an alternative non-pharmacologic intervention that has been shown to be 
effective in treating osteoarthritis5, irritable bowel syndrome6, and postoperative ileus7. 
Electroacupuncture (EA) evolved from conventional manual acupuncture and delivers weak 
electrical current to needles inserted into acupuncture points. Transcutaneous electrical 
acustimulation (TEA) is a needleless alternative of EA that delivers electrical stimulation 
noninvasively via surface electrodes placed on acupoints. TEA is one novel form of 
transcutaneous neuromodulation that has been shown to be a potential non-pharmacologic 
treatment option for several GI motility disorders8, 9 and acute pancreatitis10. 
The role of acupuncture methods in CP has been evaluated in 2 prior studies with conflicting 
results. The first study was conducted 3 decades ago in 23 patients with chronic abdominal pain 
due to CP and showed that both EA (5 sessions over two weeks) and transcutaneous electrical 
nerve stimulation (TENS, daily stimulation over 3 weeks using carbon rubber electrodes) failed 
to show any significant effects on pain as compared to sham treatments.11 In a more recent study 
of 15 patients with painful CP, one session of traditional acupuncture led to more pain relief 
compared with sham stimulation.12 However, the effect was short-lived, and after 1-week follow-
up, there was no difference in clinical pain scores between groups. These conflicting results are 
likely due to the selection of different stimulation points, stimulation parameters and treatment 
durations. Similar to other medical therapies, these are important factors determining the efficacy 
of the EA therapy. In addition, the mechanisms of pain in CP are complex and multifactorial, and 
some particular pain phenotypes may be more responsive to acupuncture to others.  
In this project, we will use a novel TEA device for treatment of abdominal pain in patients 
with CP. The proposed TEA is based upon a logical progression of preliminary basic 
mechanistic and clinical studies.10, 13, 14 We will use specific parameters designed for treating 
abdominal pain that have been shown to be effective for ameliorating abdominal pain in patients 
with irritable bowel syndrome (IBS)15 and acute pancreatitis (AP)10. Mechanistically, TEA at 
these acupoints and with these parameters can improve autonomic function and inhibit 
inflammation. Clinically, the proposed TEA can be self-administrated at home 1 or more times 
daily. If TEA is effective in reducing pain in CP, this may be an alternative intervention with 
better safety profile to other interventions used for painful CP and an attractive non- 
pharmacological approach for opioid-free pain therapy.  
 

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2. Specific aims:  
 
Aim 1: To determine the feasibility and tolerability of delivering TEA to outpatients with painful 
CP 
 
Approach: We propose to conduct an open-label feasibility trial to understand the feasibility of 
TEA in patients with painful CP. In this open-label study, all subjects will receive TEA at 
acupoint ST36 in an unblinded manner. This will inform on recruitment & retention rates, 
percentage of patients with complete data collection and compliance with study procedures. This 
will also assist in sample size calculations for a future larger study.  
 
Aim 2: To collect pilot data on the efficacy of TEA on abdominal pain, patient reported 
outcomes, and quality of life, in patients with painful CP. TEA at ST36 has been shown to be 
effective in the treatment of patients with abdominal pain due to visceral hypersensitivity and 
pancreatic inflammation.10, 15 We will use parameter P100 (100Hz, 0.5ms, 0.1s-on and 0.4s-off, 
and tolerable current output), which has been found most effective in treating visceral pain in 
animals and patients with irritable bowel syndrome.13, 16  TEA at this acupoint may be effective 
in ameliorating pain in CP by improving pancreatic inflammation or autonomic function. 
 
3. Methods: participants, interventions, and outcomes 
 
In this study, we aim to assess feasibility of TEA, enrollment methods, and data collection tools. 
All patients will receive TEA via ST36 twice daily (a point below the knee cap) in an unblinded 
fashion. We will then use this preliminary data to apply for competitive funding to conduct a 
larger study. The population, intervention and outcome for this study are summarized in Table 1.  
 
Table 1: Summary of study population, interventions, outcomes and setting 
 
Population 
Adult subjects aged 18 to 75 years with chronic pancreatitis and 
abdominal pain 
Intervention 
Home-based 30-minute sessions of TEA twice a day for 4 weeks 
Control 
None 
Outcome 
Enrollment, retention, and data collection feasibility 
Setting 
Comprehensive pancreas clinic at the University of Michigan 
 
Eligibility criteria: 
 
Inclusion criteria 
1. Age 18 to 75 years of age. 
2. Diagnosis of chronic pancreatitis, based on a score > 4 using the previously validated Mayo 
scoring system that uses morphologic and functional criteria17, or endosonographic features 
suggestive or consistent with CP based on Rosemont criteria18.  
3. Abdominal pain present at least once a week within the last month 
4. Willing and able to provide written informed consent 
 

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Exclusion criteria 
1. Pregnancy or breastfeeding mother 
2. Imprisoned individuals 
3. Non-English speaking patients 
4. Scheduled for or with a history of pancreatic surgery (e.g. TPIAT, Puestow, Frey, Whipple, 
other) 
5. Currently undergoing or about to start endoscopic therapy with ERCP or EUS 
6. Recent history of acute pancreatitis as defined by the Revised Atlanta Classification within a 
month prior to enrollment  
7. Radiologic and clinical findings consistent with symptomatic pseudocyst, wall-off necrosis, 
infected pancreatic necrosis, or biliary obstruction within the last 6 months  
8. Self-reported daily use of opioids for > 12 months for weak opioids (codeine, tramadol and 
hydrocodone) or > 6 months for strong opioids (other opioids) in the last two years. A similar 
approach was used in a recent landmark RCT that compared endoscopic therapy vs. surgery 
in patients with painful chronic pancreatitis.19  
9. Self-reported ongoing illicit drug use or abuse 
10. Suspected or diagnosed pancreatic cancer  
11. Receiving chemotherapy for cancer 
12. Known allergy to adhesive ECG electrodes 
13. Patients with bilateral below the knee amputation 
14. Patients with lower extremity paralysis 
15. Patients are participating in another clinical trial 
16. Patients with an implantable electrical stimulation device. 
 
Interventions 
 
I. Run-in period: 2 weeks (V0) 
After initial screening (V0 – virtual or in person) and after the consent form is signed, subjects 
that fulfill eligibility criteria will be invited to participate to the study.  
 
All eligible subjects will then complete a pre-enrollment run-in period of 2 weeks. Over this run-
in period, subjects will be asked to complete a diary with information on daily severity of 
abdominal pain. Subjects will rate their worst daily abdominal pain intensity over the past 24 
hours by putting a mark on a visual analogue scale (scoring 0-10), where 0 represents “no pain” 
and 10 represents the “worst imaginable pain.” Subjects with abdominal pain severity of 4 or 
greater for at least 5 days in this run-in period will be invited for a site visit to start the 
intervention (V1). Subjects who don’t qualify for this criterion will not be invited to receive the 
intervention. A similar approach has been used in a prior RCT evaluating the role of antioxidants 
for pain in CP.20 Surveys will be completed via RedCap.  
 
II. Visit 1 (V1) 
In this initial visit, subjects will complete baseline questionnaires. This visit will either be in-
person at the main hospital in Ann Arbor or performed remotely with the study coordinator. 
After enrolling in the study, subjects will be given the TEA device and receive instructions on 
how to use this via ST36. If the participant chooses to have the visit be remote, they will receive 
the study materials by mail prior to the visit and a pregnancy test supplied by the study team. In 

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either method of visit, the participant will be given a paid return mailer to give our supplies back. 
Participants will be subjected to a pregnancy test of they are of child-bearing potential on the day 
of V1.This will be done in the clinic or self-administered by the subject at home prior to the 
Zoom appointment. Recommendation to use some form of contraception during the study and 
birth control options will be discussed. Study participants will use the TEA device for 5 minutes 
under the supervision of the study coordinator. Subjects will be asked to start the intervention 
one day after the training received during the initial visit. 
 
III. Home-based treatment period- 4 weeks 
TEA will be self-administrated at home over two daily treatment sessions of 30 minutes each.  
TEA will be performed using a device that measures about 4x6 cm (Figure 
2), and that is programmed by the study team to deliver a specified weak 
electrical signal. The subject is able to adjust the stimulation output by 
pressing the “+” or “-“ sign on the device. The stimulation output is 
adjustable, because the tolerance level varies by individuals and settings 
will be adjusted based on maximal tolerance. The maximum current output 
is 10mA. All other parameters, including frequency, pulse width, and 
time on/time off during the pulsed stimulation, will be fixed. TEA is 
similar to a transcutaneous electrical nerve stimulation (TENS) unit that 
is classified by FDA as a non-significant risk device. The device is 
powered by a small rechargeable battery and the charging will take place only when the device is 
not in use. This device has been approved for use 
in two ongoing clinical studies at UofM by the 
same investigation team (HUM00189911, 
HUM00217301). 
 
TEA will be delivered through stimulation of 
acupoint ST36, located four subject’s finger 
widths down from the bottom of the knee cap 
along the outer boundary of the shin bone 
(Figure 3). TEA will be applied to one leg at a 
time. Participants may choose to switch legs with 
each session. Participants will be informed to 
switch legs if any skin irritation occurs. Subjects 
will be asked to perform the two daily 
stimulations at least 6 hours apart but no more than 14 hours apart. This variability in the 
selected leg or time interval is not expected affect the efficacy of the intervention. Devices will 
be labeled with unique identifiers and device supply will be tracked upon dispense and retrieval 
from subjects. For the stimulation of this acupoint, one electrode will be placed right at the 
acupoint and the other electrode at 3-4 cm below the first electrode along the leg. TEA will be 
performed using parameter set P100. P100 uses intermittent pulse trains with a train on-time of 
0.1s and off-time of 0.4s (2 trains/second), and a pulse frequency of 100Hz and width of 0.5ms 
within each train, and a sensible but tolerable current output based on the patient’s tolerance 
(maximal current that the patient can tolerate without feeling discomfort or pain by the current 
used). Previous studies have shown that EA at 2 Hz accelerates the release of enkephalin, beta-
endorphin and endomorphin, while EA at 100 Hz selectively increases the release of dynorphin; 
Figure 2: Photo of the existing 
TEA device 
Figure 3: Location of ST36 for TEA 
Figure 2: Photo of the existing 
TEA device 

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a combination of the two frequencies produces a simultaneous release of all opioid peptides, 
resulting in a maximal analgesic effect.21, 22 In our Parameter set P100, there are two frequency 
components: 100Hz pulses and 2Hz trains. EA and TEA with this parameter set have been 
shown to be effective in reducing abdominal pain.13, 23, 24 Adherence will be directly monitored 
through use of the TEA device. The TEA automatically records duration of use, time of the day, 
and stimulation intensity.  
 
The treatment will be discontinued if the patient develops an adverse event (discussed under 6. 
Safety Management) that requires the treatment to be stopped or at the participant request. 
Subjects will be allowed to start and continue conventional medical therapy for the duration of 
the study, including any pain medications. This will be at the discretion of the treating physician.  
This will allow us to assess the addition of TEA to conventional care. The TEA intervention will 
be discontinued if the patient gets admitted to hospital or if a surgical or endoscopic procedure is 
performed during the treatment phase of the study. During the 4 weeks of treatment, subjects will 
complete pain diaries through RedCap. This will take 2 minutes for completion.  
 
IV. Monitoring phone calls 
To assess any potential problems with the TEA device, we will contact participants via telephone 
within 72 hours of starting treatment and then weekly at 1 week, 2 weeks, and 3 weeks from 
treatment initiation. 
 
V. Visit 2 (V2), 4 Weeks from V1 
During this follow-up period subjects will complete the same set of surveys that was completed during 
the first visit to assess pain, quality of life, and anxiety or depression. Subjects will also return the TEA 
device using their return mailer (provided during or prior to visit 1). In the event the device is broken or 
non-functional, participants will still be requested to return the device. 
 
VI. Visit 3 (V3), at 8 weeks from V1 
After subjects finish treatment (4 weeks from V1), they will continue completing daily pain diaries for 
additional 4 weeks. During this phase, subjects will not receive device stimulation. At 8 weeks from V1, 
subjects will be asked to complete the same set of surveys completed during visit 1 and 2. These will be 
completed via RedCap.  
 
VII. Close-out phone call, at end of trial 
At the end of the trial, study subjects who enrolled and received TEA will be reached out via a 
phone call to assess on global impression and acceptability of the treatment.  
 
Outcomes 
 
Primary outcomes 
 
1. Enrollment feasibility: how many patients with CP who are assessed meet eligibility criteria. 
In addition, of these, how many provide informed consent. Of those who consent, how many 
meet criteria to participate after the run-in period. Of those who meet run-in period criteria, 
how many start the intervention (TEA).   

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2. Adherence: of those who start the intervention, how many adhere to the intervention as 
prescribed. The time of the day and duration of each TEA administration will be 
automatically recorded by the TEA device.  
3. Retention feasibility: how many patients who start the intervention complete follow-up visit 
at week 4 and return complete follow-up questionnaires at week 8.  
4. Visits duration: how long does it take to complete visits 1 and 2.  
5. Data collection feasibility: how many patients complete all the surveys. In addition, we will 
calculate the proportion of study surveys that are completed per protocol 
 
Exploratory outcomes 
 
1. Pain diary records [timeframe: daily from 2-week run-in period until 8 weeks from 
treatment onset]: this will be used to measure daily pain experience on an 11-point visual 
analogue scale (VAS). The recording of daily pain scores will be started during the 2-
week run-in period and will end 8 weeks after the intervention is over. Subjects will mark 
a point along a scale (from no pain [0] to worst imaginable pain [10]) on the VAS related 
to (a) average pain and (b) worst pain during the last 24 hours on two separate entries. 
This will be done at a fixed time of the day chosen by the participant. We will measure 
the change of average and worst pain from baseline to 4 weeks and 8 weeks post-
treatment.  
2. Brief Pain Inventory—Short Form (BPI-SF) [timeframe - weekly from baseline until 8 
weeks from treatment onset]: The BPI-SF is a validated self-reported tool that evaluates 
pain severity and pain interference with daily activities at the time of assessment. A total 
of 4 pain intensity items (worst, least, average, and current pain) are rated on an 11-point 
numerical rating scale (0 = no pain, 10 = worst possible pain). The pain interference 
subscale includes 7 items evaluating the impact of pain on sleep, mood, walking ability, 
general activity, work, relationships, and enjoyment of life over the past 24 hours rated 
on an 11-point scale from 0 = does not interfere to 10 = completely interferes. Possible 
scores for pain severity range from 0 to 40 (higher scores reflect more severe pain); 
possible scores for pain interference range from 0 to 70 (higher scores reflect more pain 
interference with daily life). 
3. Comprehensive Pain Assessment Tool Short Form for Chronic Pancreatitis (COMPAT-
SF) [timeframe - baseline, 4 weeks from treatment onset, 8 weeks from treatment onset]: 
The COMPAT-SF is a validated self-reported tool specifically designed for patients with 
pancreatic disease. The COMPAT-SF carries several sub-scores for pain pattern, pain 
severity, pain provocation, pain spreading, and pain description. The pain pattern scale 
ranges from 50-100 with higher scores denoting worse pain. The severity score ranges 
from 0-100 with higher scores denoting worse pain. The provocation score ranges from 
0-70 with higher scores denoting worse pain. The spreading score ranges from 0-90 with 
higher scores denoting worse pain. The description score ranges from 0-80 with higher 
scores denoting worse pain. The total score ranges from 15-90 with higher scores 
denoting worse pain. 
4. Number of patients using prescription opioids for pain control at time of assessment 
[timeframe - baseline, 4 weeks from treatment onset, 8 weeks from treatment onset]: 
Opioid use (yes/no binary answer) at each assessment. 

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5. Mean reported daily opioid dose for patients using prescription opioids at time of 
assessment [timeframe - baseline, 4 weeks from treatment onset, 8 weeks from treatment 
onset]: Opioid dose (continuous variable in milligrams of morphine equivalent) at each 
assessment. 
6. Overall Quality of Life [timeframe - baseline, 4 weeks from treatment onset, 8 weeks 
from treatment onset]: Overall quality of life will be assessed using the PROMIS-29 
instrument. The PROMIS-29 instrument incorporates 7 domains: physical functioning, 
fatigue, pain interference, depression, anxiety, ability to participate in social roles and 
activities, and sleep disturbance. Each of these domains have a score 0-40 with higher 
scores representing worse quality of life in these domains. There are also 2 summary 
scores: Physical Health and Mental Health. Z-scores are calculated for these two 
summary scores with lower scores representing better quality of life. 
7. Change from baseline on the Hospital Anxiety and Depression Scale (HADS) [timeframe 
- baseline, 4 weeks from treatment onset, 8 weeks from treatment onset]: The HADS is a 
validated self-reported tool that screens for symptoms of anxiety and depression. Possible 
scores range from 0 to 21 (higher scores reflect more severe symptoms of anxiety or 
depression). 
8. Rates of hospital admission for pancreatitis-related hospital admissions [timeframe – 8 
weeks from treatment onset] 
9. Rates of treatment-related adverse events [timeframe - 4 weeks from treatment onset] 
10. Patient global impression of change (PGIC) [timeframe: end of follow-up]: this is a 1-
item question that should take less than 1 minute to complete. This question assesses the 
overall change on pain by using a 7-point Likert scale that ranges from (1) very much 
improved to (7) very much worse. 
11. Modified abbreviated acceptability rating profile [timeframe: end of follow-up]: this is an 
8-item questionnaire that should take 2 minutes (Tarnowski KJ, Simonian SJ. Assessing 
treatment acceptance: the Abbreviated Acceptability Rating Profile. J Behav Ther Exp 
Psychiatry 1992;23:101-6). Each item uses a 5-point Likert scale, including Strongly 
disagree, Disagree, Neutral, Agree, and Strongly agree. A final score ranges from 0-40, 
with 40 indicating the highest acceptability possible. This will serve to assess how study 
subjects perceive the acceptability of the TEA treatment for pain in CP.  
 
Participant timeline 
 
After enrollment, participants will have a 2-week run-in period, where they will complete daily 
pain diaries. If participants fulfill minimal pain requirements, participants will  complete V1 to 
provide baseline data and will start TEA treatment. Participants will undergo TEA therapy twice 
a day for 4 weeks. During that time, participants will continue completing daily pain diaries and 
will 3 weekly phone calls to assess adverse events. After 4 weeks of TEA therapy, the 
participants will return the device and will complete V2, in which participants will complete 
questionnaires similar to V1. Participants will then continue completing daily pain diaries for 
additional 4 weeks, while not receiving the TEA therapy. At completion of those 4 weeks, 
participants will have closure V3, in which they will provide questionnaires similar to V1 and 
V2. The total participant’s duration in the study is 10 weeks (2 weeks run-in, 4 weeks TEA 
treatment, and 4 weeks post TEA treatment assessment). At the end of the trial, participants will 
receive a close-out phone call to assess treatment acceptability. 

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Table 2: schedule of study visits 
 
Visit ID 
V0 
V1 
Phone 
call 1 
Phone 
call 2 
Phone 
call 3 
Phone 
call 4 
V2 
V3 ^ 
Close-out 
Target time 
- 2 weeks 
0 
Within 
72h 
+1w 
+2w 
+3w 
+4 weeks 
+8 
weeks 
End of trial 
Time window 
2 weeks 
+ 1 week 
 
 
 
 
+ 1 week 
+ 1 week 
 
Procedure  
 
 
 
 
 
 
 
 
 
Eligibility evaluation 
x 
 
 
 
 
 
 
 
 
Medical history and 
demographics  
x 
 
 
 
 
 
 
 
 
Consent 
x 
 
 
 
 
 
 
 
 
Pain diary (daily average 
& worse pain, weekly BPI-
SF) 
x 
x 
 
 
 
 
x 
x 
 
Pain assessment 
(COMPAT-SF, opioids) 
 
x 
 
 
 
 
x 
x 
 
Quality of life (PROMIS-
29) 
 
x 
 
 
 
 
x 
x 
 
Anxiety and depression 
(HADS) 
 
x 
 
 
 
 
x 
x 
 
Adverse events 
 
 
x 
x 
x 
x 
x 
 
 
Pancreatitis-related 
hospital admissions 
 
 
 
 
 
 
x 
x 
 
Patient global 
impression of change 
(PGIC) 
 
 
 
 
 
 
 
 
x 
Modified abbreviated 
acceptability rating 
profile 
 
 
 
 
 
 
 
 
x 
 
Recruitment 
Participants will be identified using different methods. 1) We will use DataDirect to identify 
potential participants with chronic pancreatitis who do not have major exclusion criteria and who 
are actively following at the University of Michigan. This will provide a retrospective list of 
patients with chronic pancreatitis seen at the University of Michigan in the past 1 year. 2) The 
study coordinator will also identify potential participants from the list of patients scheduled for 
clinic visits with Dr. Machicado, Dr. DiMagno, or other members of the pancreas clinic. This 
will be done using MiChart. 3) The study investigators (Drs. Machicado and Dr. DiMagno) and 
physician colleagues seeing patients at the Comprehensive Pancreas Program will refer potential 
subjects to the study team. The research team will review potential study participants' medical 
history through the electronic medical record (MiChart) to assess patients’ eligibility.  
 
Once a subject is identified through any of the above methods, the subject will be contacted by 
phone using a phone script or approached in person in the outpatient clinic. The study team will 
follow a script and go through the pre-screen questions. If the patient is determined to be 
ineligible via the pre-screen questions they will be excluded from the study and logged as 
contacted by the study team but ineligible to participate. In doubt, the study investigator will 

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determine eligibility. If the subject meets eligibility criteria, the subject will be invited to 
participate in the study. If the subject is interested, an informed consent will be given either in 
person if the subject is in clinic or mailed for review & signature via eConsent or SignNow. 
 
 
4. Methods: data collection 
 
All data will be collected using active and passive methods, including patient interviews, 
physical examinations, and review of electronic medical records. A trained research coordinator 
will collect data using standardized forms via RedCap. Research coordinators will follow the 
manual of operations for all study procedures. All forms will include essential instructions and 
definitions of variables.  
 
A. Pre-screening form: this will include questions on inclusion and exclusion criteria, pertinent 
for study eligibility. Initial screening will be based on chart review, in person or telephone 
patient interview, endoscopic results, and radiologic data that are consistent with the study 
definition of CP. Screening data will be obtained by the research coordinator before enrollment. 
This is uploaded into section 8-1.8 
 
B. Pain diary: this will be directly completed by patients. Daily pain scores will be recorded 
during the 2-week run in period. In those patients who are eligible and are started in TEA, 
patients will complete the pain diary for 4 weeks during the TEA therapy and will continue for 4 
weeks after the intervention is over. The patients will report (a) average pain during the last 24 
hours using a VAS, (b) maximal pain during the last 24 hours using a VAS, and (c) weekly BPI-
SF (only after intervention started). The survey is uploaded into section 29.1.  
 
C. Baseline form: this will include data on demographics, clinical profile of CP, laboratory 
biomarkers, radiologic findings, and prior therapeutic interventions, all of which will be recorded 
from the medical records and by patients filling up a survey. In addition, patients will complete a 
form pertaining to pain, quality of life, anxiety and depression using the instruments described in 
secondary outcomes.  
 
D. First follow-up form: this form will be used to assess pain, quality of life, anxiety and 
depression after the intervention, using the instruments described in secondary outcomes. 
Adverse events of the intervention will also be recorded in this form. These surveys are uploaded 
into section 29.1.  
 
E. Second follow-up form: This form will be given to participants during the first follow-up 
(V2). Subjects will be asked to complete and mail the follow-up questionnaires and diary. This 
form will be used to assess pain, quality of life, anxiety and depression after the intervention has 
been discontinued. These surveys are uploaded into section 29.1. 
 
All data will then be captured in a password-protected database through Redcap. Several 
methods will be used to promote data quality and integrity including database development, 
proper training of study team members, and use of data quality rules and validation. Each subject 
will be assigned a unique random number, and Protected Health Information will be coded to 

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ensure no one outside the study team will be able to identify a subject’s identity. This database 
will be stored in a password-protected database, in a password-protected folder on a secure 
server behind the University of Michigan firewall. The information will, at all times, only be able 
to be accessed by the study investigators. 
 
F. After enrollment is completed, study subjects who enrolled and received TEA will be reached 
out via a phone call to assess on global impression and acceptability of the treatment. Study 
subjects will be asked the following questions in relation to the use of TEA on their chronic 
pancreatitis pain.  
  
- Patient global impression of change (PGIC): this is a 1-item question that should take less than 
1 minute 
- Modified abbreviated acceptability rating profile: this is an 8-item questionnaire that should 
take 2 minutes (Tarnowski KJ, Simonian SJ. Assessing treatment acceptance: the Abbreviated 
Acceptability Rating Profile. J Behav Ther Exp Psychiatry 1992;23:101-6). 
- Two open questions: (i)“How did the TEA device help you in managing your pancreatitis 
pain?” and (ii)“What modifications would you suggest to improve the TEA treatment?" 
 
 
5. Statistical methods 
 
Sample size calculation 
 
We will conduct an open-label pilot study of 10 subjects with CP that fulfill eligibility criteria 
and that receive the TEA device during visit 1. This will serve to inform feasibility on 
enrollment, adherence, retention, and completion of data collection. Data obtained in this study 
will lead to protocol changes for a larger randomized controlled trial that we will plan in the 
future. The study will be under powered to address any clinical outcomes. We anticipate attrition 
of approximately 10% for a study of this nature.  
 
Statistical analysis 
 
All analyses will be performed according to the intention-to-treat principle. All primary 
outcomes will be measured using descriptive statistics as absolute values (percentage), mean ± 
standard deviation (SD), and median (interquartile range [IQR]), as appropriate.  
 
Primary outcomes 
 
A. Enrollment feasibility:  
• Proportion of approached participants who meet eligibility criteria.  
• Proportion of those who meet eligibility criteria and who provide informed 
consent 
• Proportion of participants who meet the criteria after the run-in period among 
those who provided informed consent.  
• Proportion of participants who start the intervention among those who meet run-in 
period criteria.   

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B. Adherence: proportion of participants who adhere to the intervention as prescribed 
among those who start the intervention 
 
C. Retention feasibility: proportion of patients who complete follow up visit at 4 weeks and 
return complete follow-up questionnaires at week 8, among those who started the 
intervention 
 
D. Visit duration:  
 
• For visit 1, median (IQR) of the time that takes to complete visit 1.  
• For visit 2, the median (IQR) of the time that takes to complete visit 2.  
 
E. Data collection feasibility:  
• Proportion of participants who come for visit 1 and complete all the surveys 
involved in the study.  
• Proportion of study surveys that are completed per protocol 
 
Exploratory endpoints 
 
• Worst pain on visual analogue scale  
• Mean ± SD of worst pain during the run-in period (baseline) 
• Mean ± SD of worst pain during the treatment period (week 0-4) 
• Mean ± SD of worst pain during the last week of treatment (week 4) 
• Mean ± SD of worst pain after completion of treatment (week 5-8) 
• Mean ± SD of worst pain during the last week without treatment (week 8) 
• Mean difference of worst pain score from the last week of treatment compared to baseline 
worst pain.  
• Rank-sum test or paired t test depending on data distribution to compare worst pain score 
from the last week of treatment compared to baseline worst pain.  
• Mean difference of worst pain score after completion of treatment compared to worst 
pain during the last week of treatment 
• Rank-sum test or paired t test depending on data distribution to compare worst pain score  
after completion of treatment compared to pain severity from the last week of treatment.  
 
• Average pain on visual analogue scale 
• Mean ± SD of average pain during the run-in period (baseline) 
• Mean ± SD of average pain during the treatment period (week 0-4) 
• Mean ± SD of average pain during the last week of treatment (week 4) 
• Mean ± SD of average pain after completion of treatment (week 5-8) 
• Mean ± SD of average pain during the last week without treatment (week 8) 
• Mean difference of average pain score from the last week of treatment compared to 
baseline average pain.  
• Rank-sum test or paired t test depending on data distribution to compare average pain 
score from the last week of treatment compared to baseline average pain.  

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• Mean difference of average pain score after completion of treatment compared to average 
pain during the last week of treatment 
• Rank-sum test or paired t test depending on data distribution to compare average pain 
score after completion of treatment compared to pain severity from the last week of 
treatment.  
 
• Pain severity on BPI-SF 
• Mean ± SD of pain severity during the run-in period (baseline) 
• Mean ± SD of pain severity during the treatment period (week 0-4) 
• Mean ± SD of pain severity during the last week of treatment (week 4) 
• Mean ± SD of pain severity after completion of treatment (week 5-8) 
• Mean ± SD of pain severity during the last week without treatment (week 8) 
• Mean difference of pain severity from the last week of treatment compared to baseline 
pain severity.  
• Rank-sum test or paired t test depending on data distribution to compare pain severity 
from the last week of treatment compared to baseline pain severity.  
• Mean difference of pain severity after completion of treatment compared to pain severity 
during the last week of treatment 
• Rank-sum test or paired t test depending on data distribution to compare pain severity 
after completion of treatment compared to pain severity from the last week of treatment.  
 
Pain interference on BPI-SF 
• Mean ± SD of pain interference during the run-in period (baseline) 
• Mean ± SD of pain interference during the treatment period (week 0-4) 
• Mean ± SD of pain interference during the last week of treatment (week 4) 
• Mean ± SD of pain interference after completion of treatment (week 5-8) 
• Mean ± SD of pain interference during the last week without treatment (week 8) 
• Mean difference of pain interference from the last week of treatment compared to 
baseline pain interference.  
• Rank-sum test or paired t test depending on data distribution to compare pain interference 
from the last week of treatment compared to baseline pain interference.  
• Mean difference of pain severity after completion of treatment compared to pain severity 
during the last week of treatment 
• Rank-sum test or paired t test depending on data distribution to compare pain severity 
after completion of treatment compared to pain severity from the last week of treatment.  
 
• Pain by COMPAT-SF 
• Mean ± SD of COMPAT-SF score at onset of treatment (at baseline during visit 1) 
• Mean ± SD of COMPAT-SF score at end of treatment (at 4 weeks during visit 2) 
• Mean ± SD of COMPAT-SF score at end of follow-up without treatment (at 8 weeks) 
• Mean difference of COMPAT-SF score from end of treatment compared to score at 
baseline. 
• Rank-sum test or paired t test depending on data distribution to compare COMPAT-SF 
score from end of treatment compared to baseline score 

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•  Mean difference of COMPAT-SF score at end of follow-up without treatment compared 
to score at baseline 
• Rank-sum test or paired t test depending on data distribution to compare COMPAT-SF 
score from end of follow-up without treatment compared to baseline score 
• Mean difference of COMPAT-SF score at end of follow-up without treatment compared 
to score at end of treatment 
• Rank-sum test or paired t test depending on data distribution to compare COMPAT-SF 
score from end of follow-up without treatment compared to score at end of treatment 
 
• Proportion of patients using opioids 
• Proportion of patients using prescription opioids for pain control at onset of treatment (at 
baseline during visit 1) 
• Proportion of patients using prescription opioids for pain control at end of treatment (at 4 
weeks during visit 2) 
• Proportion of patients using prescription opioids for pain control at end of follow-up 
without treatment (at 8 weeks) 
• McNemar Test to compare proportion of patients using opiates at end of treatment 
compared to baseline 
• McNemar Test to compare proportion of patients using opiates at end of follow-up 
without treatment compared to baseline 
• McNemar Test to compare proportion of patients using opiates at end of follow-up 
without treatment compared to end of treatment 
 
• Reported dose of opiates b y milligrams of morphine equivalent (MME) 
• Mean ± SD of MME at onset of treatment (at baseline during visit 1) 
• Mean ± SD of MME at end of treatment (at 4 weeks during visit 2) 
• Mean ± SD of MME at end of follow-up without treatment (at 8 weeks) 
• Mean difference of MME from end of treatment compared to baseline. 
• Rank-sum test or paired t test depending on data distribution to compare MME from end 
of treatment compared to baseline  
• Mean difference of MME at end of follow-up without treatment compared to baseline 
• Rank-sum test or paired t test depending on data distribution to compare MME from end 
of follow-up without treatment compared to baseline  
• Mean difference of MME at end of follow-up without treatment compared to MME at 
end of treatment 
• Rank-sum test or paired t test depending on data distribution to compare MME from end 
of follow-up without treatment compared to MME at end of treatment 
 
• Physical quality of life (QOL) 
• Mean ± SD of physical QOL at onset of treatment (at baseline during visit 1) 
• Mean ± SD of physical QOL at end of treatment (at 4 weeks during visit 2) 
• Mean ± SD of physical QOL at end of follow-up without treatment (at 8 weeks) 
• Mean difference of physical QOL from end of treatment compared to baseline. 
• Rank-sum test or paired t test depending on data distribution to compare physical QOL 
from end of treatment compared to baseline  

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• Mean difference of physical QOL at end of follow-up without treatment compared to 
baseline 
• Rank-sum test or paired t test depending on data distribution to compare physical QOL 
from end of follow-up without treatment compared to baseline  
• Mean difference of physical QOL at end of follow-up without treatment compared to 
physical QOL at end of treatment 
• Rank-sum test or paired t test depending on data distribution to compare physical QOL 
from end of follow-up without treatment compared to physical QOL at end of treatment 
 
• Mental quality of life (QOL) 
• Mean ± SD of mental QOL at onset of treatment (at baseline during visit 1) 
• Mean ± SD of mental QOL at end of treatment (at 4 weeks during visit 2) 
• Mean ± SD of mental QOL at end of follow-up without treatment (at 8 weeks) 
• Mean difference of mental QOL from end of treatment compared to baseline. 
• Rank-sum test or paired t test depending on data distribution to compare mental QOL 
from end of treatment compared to baseline  
• Mean difference of mental QOL at end of follow-up without treatment compared to 
baseline 
• Rank-sum test or paired t test depending on data distribution to compare mental QOL 
from end of follow-up without treatment compared to baseline  
• Mean difference of mental QOL at end of follow-up without treatment compared to 
mental QOL at end of treatment 
• Rank-sum test or paired t test depending on data distribution to compare mental QOL 
from end of follow-up without treatment compared to mental QOL at end of treatment 
 
• Hospital anxiety and depression scale (HADS) 
• Mean ± SD of HADS score at onset of treatment (at baseline during visit 1) 
• Mean ± SD of HADS score at end of treatment (at 4 weeks during visit 2) 
• Mean ± SD of HADS score at end of follow-up without treatment (at 8 weeks) 
• Mean difference of HADS score from end of treatment compared to baseline. 
• Rank-sum test or paired t test depending on data distribution to compare HADS score 
from end of treatment compared to baseline  
• Mean difference of HADS score at end of follow-up without treatment compared to 
baseline 
• Rank-sum test or paired t test depending on data distribution to compare HADS score 
from end of follow-up without treatment compared to baseline  
• Mean difference of HADS score at end of follow-up without treatment compared to 
HADS score at end of treatment 
• Rank-sum test or paired t test depending on data distribution to compare HADS score 
from end of follow-up without treatment compared to HADS score at end of treatment 
 
• Pancreatitis related hospitalizations 
• Proportion of patients who had a pancreatitis related hospitalization during the treatment 
period 

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• Proportion of patients who had a pancreatitis related hospitalization during the follow up 
period without treatment 
• Proportion of patients who had a pancreatitis related hospitalization during the study 
period 
 
• Adverse events 
• Proportion of patients who had an adverse event due to the intervention 
 
•  Patient Global Impression of Change 
• Proportion of patients who consider their pain improved (PGIC ≤3) 
 
• Treatment acceptability 
• Proportion of patients who agree or strongly agree that the treatment was an acceptable 
intervention for dealing with chronic pancreatitis pain 
 
For missing data, we will use multiple imputation methods.  Statistical significance will be 
defined as P<0.05. 
 
6. Safety management 
Safety monitoring 
The risks of TEA are minor, including possible allergic response to the standard ECG electrodes. 
The likelihood of this risk is low, approximate incidence of <1%. Since TEA uses current flow 
through the skin, there is a possibility of uncomfortable sensation or pain at the skin, abnormal or 
involuntary movements (chorea, dystonia, dyskinesia), gastrointestinal disturbances or nausea. 
However, the stimulation output will be set at a level that is well tolerated by the participant. In 
very rare occasions, the participant might experience rash or minor infection at the stimulation 
point that can be treated locally if needed. If this occurs, the device can be moved to the opposite 
leg at the same location. If the patient develops a local rash or minor infection in the opposite 
leg, the patient will discontinue the treatment and notify the study team. To protect subjects 
against risks, subjects will be instructed to avoid manipulating or rubbing the electrodes to avoid 
any electrode deformations or breakage.  Subjects will be instructed to stop the TEA therapy 
immediately once they experience uncomfortable sensation or pain at the electrode site.  
 
Participants may develop discomfort related to reporting daily symptoms and repeated surveys 
where they are asked about their health and well-being. In order to decrease this risk, the number 
of surveys have been prioritized to the most relevant surveys necessary to assess compliance. 
Finally, there is a risk for embarrassment from responding to the questionnaires, as many of the 
questions are pertaining to negative experiences such as pain, anxiety, depression, and quality of 
life. The participants will be allowed to skip question that cause them to feel discomfort.  
 
Finally, there is a small risk of compromised confidentiality, which is associated with analysis 
and sharing of medical data. The likelihood of this risk is low, estimated to be <1%. To reduce 
this risk, each subject will be assigned an ID number, and all data will be stored with the subject 
ID number only and not the subject’s name. All data records entered into the study electronic 
data capture (EDC) system will be stored on the HIPAA- compliant cloud data server, which is 

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encrypted and password protected, and the EDC system will comply with the 21 CFR Part 11 
requirements for electronic record keeping. All locally-stored data will be on a password-
protected computer. Subject charts with medical history and assigned subject numbers will be 
kept in locked file cabinets stored at the clinical site. Access to charts will be granted only to 
study investigators. Charts will be kept confidential and will not be shared with any third parties 
without permission from the subject. 
Patients who develop a serious adverse event (SAE), as defined by the Food Drug 
Administration (FDA) 25, will have the study intervention discontinued, and be managed 
medically as deemed appropriate by the patient’s clinical team. A SAE is defined by the FDA if 
the AE results in any of the following outcomes: death, a life-threatening AE, inpatient 
hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or 
substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. For related, unexpected, serious device events resulting in death and life 
threatening outcome (per IRBMED guidelines) these will be submitted as soon as possible but 
within 7 calendar days of becoming aware of the event. 
The study team will submit to the reviewing IRB a report of any unanticipated adverse device 
effect occurring during an investigation as soon as possible, but in no event later than 14 
calendar days after the investigator first learns of the effect. 
7. Ethics and dissemination 
 
TEA is similar to a transcutaneous electrical nerve stimulation unit that is classified by FDA as a 
non-significant risk device. Therefore, an investigational device exemption (IDE) for the FDA 
will not be needed.  
 
The study will require approval by the IRB of the University of Michigan. Any protocol 
amendments will be communicated to the IRB. Informed consent will be obtained by the study 
coordinator face to face or by phone from eligible participants or authorized surrogates. If 
consent is obtained remotely, subjects will be sent a copy of the consent via mail and sign the 
consent virtually using eConsent or SignNow. Data will be captured in a password protected 
database. Each subject will be assigned a unique random number, and Protected Health 
Information will be de-identified after complete data extraction. The final dataset will only be 
accessible by the primary investigator and data analyst.  
 
The final results may be presented at meetings, in publications, or in future funding applications; 
however, such presentations will be of aggregate data only without disclosure of any individual 
subject identities or PHI. The results of the trial will be posted in Clinicaltrials.gov. After study 
results are disseminated, deidentified participant data and the analytic code can be requested by 
external researchers to the principal investigator.  
 
8. Timeline and feasibility 
 
Over the past 3 years, the Comprehensive Pancreas Program of the University of Michigan has 
provided care to 314 new patients with CP or roughly 104 new patients per year. In addition, our 
program provides longitudinal care to patients with CP, resulting in 608 return visits for CP over 
the past 3 years or roughly 203 returns visits per year. Among these patients, it is expected that 

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87% have chronic abdominal pain.26 Dr. Jiande Chen (CO-I), leads two research studies using 
TEA in patients with irritable bowel syndrome and diabetic gastroparesis as the University of 
Michigan (HUM00189911, HUM00217301).  
 
Our proposed timeline is to complete the study in 12 months. This study will ensure feasibility of 
interventions, enrollment methods, and data collection tools. Results of this study will support a 
larger and longer study.   
 
 
9. References 
 
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Machicado JD, Amann ST, Anderson MA, et al. Quality of Life in Chronic Pancreatitis is 
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Juel J, Liguori S, Liguori A, et al. Acupuncture for Pain in Chronic Pancreatitis: A Single-
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