QST Study: Predicting Treatment Response in Chronic Pancreatitis Using Quantitative Sensory Testing
Phase: NA
Conditions: Chronic Pancreatitis, Chronic Pain
Sponsor: Anna Evans Phillips

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Title: Predicting treatment response in Chronic Pancreatitis using Quantitative Sensory Testing  
 
Date: January 3, 2018 
 
 

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Predicting treatment response in Chronic Pancreatitis using Quantitative Sensory Testing  
  
Objective: 
Endoscopic therapy or surgery for treatment of pain is typically offered to chronic pancreatitis (CP) 
patients with pancreatic ductal strictures and/or stones. However, clinical pain symptoms correlate poorly 
with pancreatic ductal morphology, response to endoscopic or surgical therapy is unpredictable, and the 
rationale for invasive therapies is often questioned.  
 
Quantitative sensory testing (QST) can map the pain system; the technique is based on the rationale that 
different neural pathways and networks can be explored using standardized stimulation and simultaneous 
recording of the evoked pain response by psychophysical and/or objective methods.  We hypothesize that 
endoscopic or decompressive surgical therapy is most effective for patients with local sensitization 
without systemic or abnormal activation of the central pain system.  Our objective is to distinguish 
phenotypes characterized by segmental sensitization of the pancreatic viscerotome (T10), and systemic 
sensitization with pathological central pain processing including augmented temporal summation and 
impaired descending pain inhibition.  
 
Aims:  
Aim 1) Investigate the association between QST profiles and demographic and clinical characteristics 
including depression and anxiety questionnaires in patients with suspected or definite CP. 
Aim 2) Investigate if the QST profile of the individual patient can be used to predict the clinical outcome 
of endoscopic or surgical treatment in patients with suspected or definite CP. 
Aim 3) Investigate the temporal evolution and association of QST profiles and clinical pain scores after 
endoscopic or surgical treatment in patients with suspected or definite CP.  
 
Background 
Treatment of pain in patients with CP is challenging and different treatments are offered to patients based 
on tradition and knowledge from other pain syndromes. In some patients, treatment is based on 
pathogenesis and when obvious duct changes, stones and strictures are present (large duct disease), 
surgery and endoscopic procedures with and without extracorporeal shock wave lithotripsy (ESWL) has 
been used successfully (Löhr et al. 2017). These procedures are to some extent mechanism based, as they 
aim to improve the flow of pancreatic juice or reduce inflammation. However, recent studies have not 
found a relation between the micro-or macrostructure and the pain intensity and therefore the 
pathophysiological evidence can be questioned (Frøkjær et al. 2013; Wilcox et al. 2015). It should also be 
noted that the marked placebo effect of the different treatment cannot be neglected and future research 
should aim to identify individual responders and if possible (such as in endoscopic procedures with stent 
placement) to include a sham arm in the studies. On the other hand, the many case reports and 
observational studies of pain improvement after invasive procedures cannot be neglected. Furthermore, 
evidence from studies in somatic tissues with peripheral nerve injury and painful polyneuropathy, also 
suggest that primary afferent input is critical for maintaining the neuropathic pain (Haroutounian 2014), 
and as such this provides a mechanistic rationale for treatment in patients with duct obstruction.  
 
The Nijmegen Aalborg Screening QST Paradigm (NASQ) has been developed in collaboration between 
groups in Holland and Denmark to replace cumbersome and highly technological methods for visceral 
pain stimulation with a simpler paradigm that can be used at bedside. The method uses in its original 
design quantitative sensory testing (QST) with tetanic electrical and pressure stimulation at different 
dermatomes in order to unravel the pain system. Furthermore, it includes assessment of descending 
inhibition with pressure stimulation before and after a “conditioning stimulus” with the hand immersed 
into ice water (conditioned pain modulation, CPM). In order to detect changes in the pain system with 
NASQ we have previously used postoperative pain as a model, as the painful event (the surgery) is 
planned and controlled, and therefore the changes in the nociceptive system can be followed 

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systematically. After surgery, it has been shown that the initial changes in pain processing (using the 
NASQ) in the days after surgery can predict who will develop chronic postsurgical pain (Wilder-Smith 
2015). For example, we recently showed that early postoperative hyperalgesia to pressure stimulation in 
the first days after surgery was an independent risk factor for development of chronic pain (van Helmond 
et al. In preparation 2016).  
 
In CP, we have used NASQ to detect differences in generalised sensitization (overall difference between 
the blue and green curves in figure 1) as well as changes in the sensation between different dermatomes 
(for example the hyperalgesia at T10 in figure 1) together with assessment of CPM. Hence, we have 
showed that patient with increased sympathetic drive have increased pain to QST in general (Buscher et 
al. 2010), and the degree of generalised sensitization correspond with the MANNHEIM severity index 
(the more diseased, the more pain) as well as response to splanchnicectomy  (Bouwense et al. 2011; 
Bouwense et al. 2013). The methods have also been used to guide treatment, as selective sensitization at 
the pancreatic dermatome (T10) rather than generalized sensitization was shown to predict the effect of 
pregabalin (Olesen et al. 2013). We have also shown that patients with CP suffer from deficient 
descending inhibition as reflected in CPM. Drugs such as tapentadol and venlafaxine may potentiate this 
mechanism in patients with neuropathy (Yarnitski et al. 2012; Niesters et al. 2015). We therefore believe 
that these drugs are helpful in many patients with pain due to pancreatitis, where a large fraction is 
thought to have neuropathic pain (Drewes et al. 2008).   
 
Notably, QST profiles from CP patients have been reported only in Europeans to date: no data exist at this 
time on CP patients in the United States.  
 
 
 
 
 
 
 
 
 
 
Methodological aspects: The pressure and electrical stimulations were previously shown to be 
reproducible in patients with CP (figure 2) whereas the CPM was not (Olesen et al. 2012). On the other 
hand, this is an inherent problem with all methods to evoke descending inhibition (even in healthy 
volunteers) and is not restricted to CP. As many patients are reluctant towards the electrical stimulation 
and the methods also are technically more demanding, we compared in a pilot study pain assessment 
between electrical and pressure stimulation at different dermatomes. As can be seen in figure 3 there is 
limited gain using electrical stimulation as compared with pressure when the pain tolerance thresholds are 
used. In the newest version of NASQ we also added pinprick stimulation with the possibility to address 
“temporal summation”. This is a method that corresponds to “wind-up” in preclinical studies and is 
suitable to study central sensitization. When temporal summation is used in patients with a sensitized pain 
system they show increased pain response to repeated stimuli at the same intensity delivered with a 
frequency above 0.3 Hz. Temporal summation has also been shown to reflect central sensitization in 
patients with pain due to CP (Dimcevski et al. 2007). We therefore suggest that the modified NASQ will 
consist of the following: 
1) the mechanical pain with the pressure device at the different dermatomes shown in figure1  
2) temporal summation with the standardized pin-prick instrument  
3) assessment of CPM with pressure (same device as 1) before and after immersion of the hand in ice-
water.  
Figure 1. The different dermatomes 
tested (left) and a profiling of controls 
and patients with different degree of 
sensitization to pressure pain 
stimulation (right) 

Versi o n 1. 3. 2 0 1 8  
 
4  
 
T et a nic el ectric s,
m ul a, o n
Pr ess ur e s,
m ul a, o n
T his is d oa ble i n a b o ut 2 0 mi n after trai ni n g, b ut t o e ns ure reas o na ble re peata bilit y it nee ds  t o be i n t he 
ha n d of fe w pers o ns. T he Q S T s hall be s u p p orte d b y q uesti o n naires t o - 
4) assess de pressi o n ( usi n g e. g., H os pital A n xiet y a n d De pressi o n Scale, Bjella n d et al. 2 0 0 2) a n d  
5) sit uati o nal catastr o p hizi n g after t he c ol d  water test ( Gr ose n  et al. 2 0 1 6). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Si g nific a nce:  
T he st u d y ma y all o w us t o p he n ot y pe patie nts base d o n t heir Q S T fi n di n gs i n or der t o better u n dersta n d 
a n d treat t he pai n s y n dr o mes t hat occ ur i n t he setti n g of C P.   It ma y als o all o w us t o pre dict t he res p o nse 
of p he n ot y pe d patie nts t o e n d osc o pic a n d s ur gical i nter ve nti o ns f or C P.  We w o ul d a ntici pate f urt her 
cli nical trials wit h t his tec h ni q ue t o m ore acc uratel y u n dersta n d t hese pai n s y n dr o mes a n d el uci date 
patter ns i n ot her p o p ulati o ns.  
 
St u d y P artici p a nts:  
1)  S u bjects wit h n o p a ncre atic dise ase a n d n o a b d o mi n al p ai n , or  p atie nts wit h a di a g n osis of  
f u ncti o n al d ys pe psi a.  
I ncl usi o n Criteri a:  
Fi g ure 2 . Re pr o d uci bility of press ure 
p ai n at t he p ai n detecti o n t hres h ol d 
( P D T, left) a n d p ai n t oler a nce t hres h ol d 
( P T T, ri g ht) –  f or det ails, see Olese n et 
al. 2 0 1 2  
 
Fi g ure 3 . Rece nt pil ot st u dies c o m p ari n g t he p ai n pr ofile i n c o ntr ols a n d p atie nts  
bet wee n differe nt d er m at o mes t o electric al (left) a n d press ur e (ri g ht) sti m ul ati o ns.  

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 
Subjects are 18 years or older in age  
 
Subjects must be able to read and understand the study information. 
 
Personally signed and dated informed consent document indicating that the subject has been 
informed of all pertinent aspects of the study. 
 
Subject is willing and able to comply with the scheduled visits, questionnaires, treatment plan, 
and other study procedures.  
     
          Exclusion criteria: 
 
Subjects with evidence or history of medical or surgical disease of importance for this study as 
judged by investigator. 
 
Subjects suffering from painful conditions that make them unable to distinguish the pain 
associated with CP from chronic pain of other origins. 
 
Subjects with known pregnancy at the time of enrolment.  
 
Subjects who have previously undergone surgical intervention on their pancreas. 
 
2) Suspected CPs  
Inclusion Criteria 
 
Subjects are 18 years or older in age  
 
Subjects with a) Indeterminate CP (Cambridge 1 or 2 on CT scan or MRI/MRCP) who have 
abdominal pain without prior history of AP, or b) those with acute (AP) or recurrent acute 
pancreatitis (RAP) who have recovered from their attack(s) of AP, whose imaging studies are 
either normal or show changes consistent with Cambridge classification of 1 or 2, and they have 
ongoing abdominal pain.   Both diabetic and non-diabetic subjects will be allowed to enter the 
study. 
 
Subjects must be able to read and understand the study information. 
 
Subjects must suffer from abdominal pain suspected to be pancreatic origin with an intensity 
above 3 on the visual analogue scale (VAS, where 0=no pain and 10= intolerable pain), and meet 
the criteria for chronic pain (pain ≥ 3 days per week for at least 3 months).  
 
Personally signed and dated informed consent document indicating that the subject has been 
informed of all pertinent aspects of the study. 
 
Subjects willing and able to comply with the scheduled visits, questionnaires, and other study 
procedures.  
           Exclusion Criteria  
 
Subjects with evidence or history of medical or surgical disease of importance for this study as 
judged by investigator. 
 
Subjects suffering from painful conditions other than pancreatitis or SOD type 1 or 2 that make 
them unable to distinguish the pain associated with pancreatitis or SOD from chronic pain of 
other origins. 
 
Subjects with known pregnancy at the time of enrolment.  
 
Subjects who have previously undergone surgical intervention on their pancreas. 
 
3) Definite Chronic Pancreatitis -  

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        Inclusion Criteria  
 
Subjects are 18 years or older in age  
 
Subjects will have a prior confirmed diagnosis of CP on CT scan or MRI/MRCP according to 
Cambridge Classification (grade 3 or 4).  Both diabetic and non-diabetic subjects will be allowed 
to enter the study. 
 
Subjects must be able to read and understand the study information. 
 
Personally signed and dated informed consent document indicating that the subject has been 
informed of all pertinent aspects of the study. 
 
Subjects willing and able to comply with the scheduled visits, questionnaires, and other study 
procedures.  
       Exclusion Criteria  
 
Subjects with evidence or history of medical or surgical disease of importance for this study as 
judged by investigator. 
 
Subjects suffering from painful conditions other than pancreatitis or SOD type 1 or 2 that make 
them unable to distinguish the pain associated with pancreatitis or SOD from chronic pain of 
other origins. 
 
Subjects with known pregnancy at the time of enrolment.  
 
Subjects who have previously undergone surgical intervention on their pancreas. 
 
4) Sphincter of Oddi Dysfunction (SOD) Type 1 or Type 2 
Inclusion Criteria 
 
Subjects are 18 years or older in age  
 
Subjects have prior diagnosis of Type 1 or Type 2 Sphincter of Oddi Dysfunction (subjects with 
biliary pain accompanied by biochemical features of transient biliary tract obstruction including 
elevated transaminases, alkaline phosphatase, or conjugated bilirubin; may also be accompanied 
by biliary or pancreatic ductal dilation on imaging)   
 
Subjects must be able to read and understand the study information. 
 
Personally signed and dated informed consent document indicating that the subject has been 
informed of all pertinent aspects of the study. 
 
Subjects willing and able to comply with the scheduled visits, questionnaires, and other study 
procedures.  
       Exclusion Criteria  
 
Subjects with evidence or history of medical or surgical disease of importance for this study as 
judged by investigator. 
 
Subjects suffering from painful conditions other than pancreatitis or SOD that make them unable 
to distinguish the pain associated with pancreatitis or SOD from chronic pain of other origins. 
 
Subjects with known pregnancy at the time of enrolment.  
 
Subjects who have previously undergone surgical intervention on their pancreas. 
 
**Note:  Women who become pregnant during the course of the study can no longer participate in QST 
testing.  
 
Study Procedures: 
 
Baseline Testing: 
All subjects will complete a basic questionnaire at baseline with assistance of a study coordinator or 
physician investigator which will collect information on demographics, pain characteristics, and 
information related to their pancreatic health.  Subjects will also complete questionnaires on quality of life 

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(PROMIS Global health Scale and EORTC-QLQ-C30), pain (modified brief pain inventory-short form 
(mBPI-sf)), psychological impact of pain (Hospital Anxiety and Depression Scale (HADS)) and 
situational catastrophizing (PCS). It will take approximately 30-60 minutes for subjects to complete the 
baseline questionnaires.  
 
All subjects will also undergo QST testing at baseline.  The procedures are described below in the section 
entitled “Experimental endpoints (quantitative sensory testing – QST).”  
 
Followup Testing: 
As part of their regular medical care, some subjects may undergo Endoscopic Ultrasound (EUS), 
Endoscopic Retrograde Cholangiopancreatography (ERCP), Extracorporeal Shock Wave Lithotripsy 
(ESWL), surgery, laboratory and imaging studies, and medical treatment.  We will review medical 
records to collect data on these variables prior to enrolment and during the course of the study.  
 
Follow-up testing will be limited to subjects who undergo endoscopic treatment or surgery for the 
pancreatitis or for SOD. These subjects will fill out a pain diary for 7 days prior to their intervention, as 
well as for seven days before each follow-up research visit at 1 month, 3 month, and 6 months post-
intervention.  The pain diary is designed to assess pain intensity and dynamics over time, and is based on 
a 0-10 NRS rating scale. Both the median and maximal pain for the last 24 hours is registered. It will take 
approximately 5 minutes per day for subjects to complete the pain diary.  These subjects will also undergo 
QST testing at each follow-up visit at 1 month, 3 months, and 6 months.  Lastly, these subjects will fill 
out the same baseline questionnaires (PROMIS, EORTC-QLQ-C30, mBPI-sf, HADS, PCS), and 
additionally the Patient’s Global Impression of Change (PGIC) questionnaire for assessment of change in 
symptoms over time.  
 
Study Timeline: Study procedures at baseline and during follow-up and which groups of study subjects 
will complete individual procedures 
 
 
Baseline 
Follow-up 
day 30  post-
intervention 
Follow-up 
day 90  post-
intervention 
Follow-up 
day 180  
post-
intervention 
QST Testing 
All Subjects 
Subjects  who 
underwent 
invasive 
intervention 
Subjects  who 
underwent  
Invasive 
intervention 
Subjects  who 
underwent 
invasive 
intervention 
Standardized 
Patient 
Questionnaires 
(PROMIS, 
EORTC, 
HADS, BPIsf, 
PCS)  
All Subjects 
Subjects  who 
underwent 
invasive 
intervention 
(Add PGIC) 
Subjects  who 
underwent 
invasive 
intervention 
(Add PGIC) 
Subjects  who 
underwent 
invasive 
intervention 
(Add PGIC) 
Pain Diary for 
7 days prior  
 
Subjects  who 
underwent 
invasive 
intervention 
Subjects  who 
underwent 
invasive 
intervention 
Subjects  who 
underwent 
invasive 
intervention 
Personal 
medical 
history 
All Subjects 
Collect 
changes from 
subjects  who 
Collect 
changes from 
subjects  who 
Collect 
changes from 
subjects  who 

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underwent 
invasive 
intervention 
underwent 
invasive 
intervention 
underwent 
invasive 
intervention 
*Intervention: endoscopic therapy or surgery 
 
Study Timeline: 
 
After informed consent the QST profile (NASQ in the figure) will be performed as seen in Figure xx.  
Follow-up QST testing as described above will only be performed in subjects who undergo endoscopic 
therapy or surgery. 
 
 
Figure 4: Study timeline 
 
 
 
 
 
Experimental endpoints (quantitative sensory testing - QST) 
Repetitive pinprick stimulation (temporal summation): Recording of temporal summation to repetitive 
pinprick stimulations in the pancreatic and control area (midline volar site of dominant forearm) will be 
employed using a 8mN PinPrick device (Pin-Prick Stimulatoren, MRC Systems GmbH, Heidelberg, 
Germany). Pain ratings using a 0-10 NRS scale will be obtained after a single application, and after the 
last application in a series of ten repetitive stimuli with an inter-stimulus interval of 1 second. For 
accurate timing of the stimuli the procedure is guided by an auditory signal using a metronome. The 
difference between the last and the first scores of the ten stimuli will be recorded as the temporal 
summation score.  
Muscle pressure stimulation: The pressure pain detection threshold (PDT) and pain tolerance threshold 
(PTT) will be determined for the following skin dermatomes: C5 (clavicula), T10 ventral (upper 
epigastric area – pancreatic viscerotome), T10 back (pancreatic viscerotome), L1 (anterior superior iliac 
crest) and L4 (the quadriceps 15 cm above the patella). All lateralized pressure stimulations are applied 
on the subject’s dominant side. An electronic pressure algometer (Algometer Type II, SBMEDIC 
Electronics, Solna, Sweden) with a probe surface area of 1 cm2 is used for the pressure stimulations. 
Pressure will be increased in two sessions at a rate of 30 kPa per second until the PDT or PTT is reached 
and subjects will be instructed to press a button at this point. The assessment parameter is the pressure at 
the predefined sensory threshold measured in kPa.  
 

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Bone pressure stimulation: The same pressure algometer as described above will be used to mechanical 
stimulation on the right tibia bone, but with a specially designed probe of 3.1 mm2 (Aalborg University, 
Denmark). The device has been used in previous studies and proven its reliability and validity20,21. 
Pressure will be applied at the tibial bone on the dominant site 10 cm distal to the lowest border of patella 
with a pressure rate at 30 kPa per second. Pain thresholds are determined as for muscle pain. 
 
Cold pressor test: The dominant hand is immersed in an ice-chilled water bucket (2.0°C ± 0.3°C). The 
subject will be told to remove the hand from the water after 2 minutes of immersion or sooner if the pain 
is intolerable. The subjects rate the pain intensity for every 10 seconds during the cold pressor test using a 
0-10 NRS rating scale. If the subject withdraws their hand sooner than two minutes, due to intolerable 
pain, the VAS will be considered to be 10 for the remaining period of time and the time for withdrawal of 
the hand will be noted.  
 
Conditioned pain modulation (CPM): CPM is a clinically measurable form of descending pain 
modulation that can be induced experimentally by a conditioning stimulus (the cold pressor test) and 
quantified by applying a “test-pain” (pressure stimulation on the non-dominant quadriceps musculature 4 
cm above the patella) before and after the conditioning stimulus22. The difference in pressure stimulus 
intensity (PTT) before and after the cold pressor test provides a quantitative index of the CPM capacity in 
the individual subject. The techniques used for pressure stimulation and cold pressor test described above 
will be combined to measure CPM. 
 
QST testing will be performed at the GI clinic or Digestive Disorders Center or the GI lab at UPMC-
Presbyterian and UPMC-Shadyside Hospital by the clinical research coordinator or a physician 
investigator. 
 
 
Device: 
Recording of temporal summation to repetitive pinprick stimulations in the pancreatic and control area 
(midline volar site of dominant forearm) will be employed using a 256 nm Von Frey Hair (Pin-Prick 
Stimulatoren, MRC Systems GmbH, Heidelberg, Germany).  
The pressure pain detection threshold (PDT) and pain tolerance threshold (PTT) will be determined for 
the following skin dermatomes: C5 (clavicula), T10 ventral (upper epigastric area – pancreatic 
viscerotome), T10 back (pancreatic viscerotome), L1 (anterior superior iliac crest) and L4 (the quadriceps 
15 cm above the patella), with an electronic pressure algometer (Algometer Type II, SBMEDIC 
Electronics, Solna, Sweden) with a probe surface area of 1 cm2 is used for the pressure stimulations.  
Bone pressure stimulation will be measured with a probe of 3.1 mm2 (Aalborg University, Denmark). The 
device has been used in previous studies and proven its reliability and validity20,21.  
 
Questionnaires to be used in the study: 
Hospital Anxiety and Depression Scale (HADS) 
PROMIS Global Health Scale (PGHS) 
Modified Brief Pain Inventory – short form (mBPI-sf) 
Pain Catastrophizing Scale (PCS) 
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-
QLQ-C30) 
Patient’s Global Impression of Change (PGIC) 
 
Clinical Outcomes: 
The primary clinical endpoint will be:  
 
QST profile of subjects with Definite or Suspected CP, SOD, Functional Dyspepsia, and controls  

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The secondary clinical endpoint will be:  
 
In subjects undergoing endoscopic or surgical treatment - The absolute and percentage change 
from baseline in ratings of average pain in the past week at day 90 using a daily pain diary based 
on a 0-10 numerical rating scale (NRS). A percentage change of ≥30% is considered clinically 
significant.  
 
Sample Size: 
Sample size determination and statistical methods 
This is an explorative pilot study and therefor no formal power calculation has been conducted.  
 
We plan to enroll a total of 500 subjects in the study, of whom at least 60 will be undergoing 
endotherapy, and at least 100 will be controls. The analysis of clinical and experimental endpoints will be 
by per-protocol, meaning that only subjects completing the experimental setup are included. The 
predictive value of the QST profiles will be analyzed using logistic regression and machine learning. 
Mixed models will be used to analyze the changes in clinical and experimental endpoints over time and 
subsequent analyses directed at the secondary clinical and experimental endpoints are analyzed using 
appropriate statistics.  
 
Patient Recruitment 
Subject with Definite or Suspected CP, SOD type 1 or 2, or Functional Dyspepsia: 
1. Subjects who are receiving care in the Digestive Disorders Center at UPMC Presbyterian-
Montefiore Hospital or GI clinic at UPMC Shadyside Hospital for Definite or Suspected CP, or 
SOD type 1 or 2, or Functional Dyspepsia, will be pre-screened for potential enrolment by the 
study team.  The study team provides clinical care to these subjects. If no exclusion criteria are 
present, and the subject meets the inclusion criteria, the study team will discuss the study with the 
subject for potential recruitment, and obtain informed consent.  
2. Subjects who are receiving care as in-patients at UPMC Presbyterian-Montefiore Hospital or at 
UPMC Shadyside Hospital for Definite or Suspected CP, or SOD type 1 or 2 will be pre-screened 
for potential enrolment by the study team.  The study team provides clinical care to these 
subjects. If no exclusion criteria are present, and the subject meets the inclusion criteria, the study 
team will discuss the study with the subject for potential recruitment, and obtain informed 
consent.  
3. Physicians and other health care professionals at UPMC Hospitals, and in the area will be made 
aware of this study at the University of Pittsburgh by means of various internal communications.  
Referring physician will discuss about the study with subjects who may be potentially eligible, 
and if they are interested will provide their information to the study team to contact.  The 
referring physicians may also ask the interested subject to contact the study team to discuss more 
about the study and potential recruitment.  If an interested subject contacts the study team, the 
clinical research coordinator or physician investigator will schedule a study visit for the subject at 
the Digestive Disorders Center Pancreas Clinic at UPMC Presbyterian-Montefiore Hospital or GI 
clinic at UPMC Shadyside Hospital to undergo screening for eligibility. The study team will 
discuss the study with the subject for potential recruitment, and obtain informed consent. If the 
subject meets the inclusion criteria and no exclusion criteria are present, the subject will be 
enrolled in the study.    
4. Subjects will be identified through the Clinical + Translational Science Institute (CTSI), via the 
Research Patient Registry. This is a voluntary database of individuals who have consented to be 
contacted for potential participation in research studies. The Registry's novel software matches 
participants, based on their demographics and ICD-9/10 codes and/or health preferences, with 
studies for which they may be eligible.   
Controls: 

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1. Controls with no pancreas disease and no abdominal pain, or who have functional dyspepsia may 
be recruited through various tools, such as advertisements (e.g. brochures, university wide 
advertisements), the CTSI research patient registry, as well as approaching subjects who come in 
for preventive services (e.g. screening colonoscopy) to the GI lab, or for evaluation for other 
unrelated conditions (gastroesophageal reflux, dysphagia, etc) to the GI clinic or Digestive 
Disorders Center.  
 
A prepared script will be read to the responders to advertisement to prescreen them for eligibility.  
If the subject agrees to participate, the coordinator will obtain a waiver to document the informed 
consent, and then ask questions regarding potential eligibility.  If the subject is eligible, the 
research coordinator will schedule a study visit to sign an informed consent and undergo a more 
thorough screening evaluation to determine if the subject meets additional criteria to participate in 
the study.  During the study visit the coordinator will review the study with the subject in detail, 
answer any questions, and if the subject is eligible, complete research related procedures.  Prior to 
any research procedure, an informed consent will be obtained by the PI or physician investigator. 
 
Subjects who are coming for screening colonoscopy or those with unrelated conditions identified 
from the Digestive Disorders Clinic will be pre-screened for potential enrolment by the study 
team.  If no exclusion criteria are present, and the subject meets the inclusion criteria, the PI or 
Physician Investigator will discuss the study with the subject for potential recruitment.  The PI or 
physician investigator and Clinical Research Coordinator will discuss with the subject about the 
study, answer any questions.  The PI or physician investigator will obtain informed consent.  
 
Subjects will be given as much time as needed to make a decision about study participation.  They are 
encouraged to take the consent form home with them and to discuss their decision with their friends, 
family, personal care physician, etc. prior to deciding about participating in the trial.  They are also 
informed by the study staff that their decisions will not affect their future care, and that their participation 
is entirely voluntary, and that they may withdraw from participation at any time.  
 
Eligible subjects will have the study explained to them in detail, and they will be provided with the 
informed consent form.  Any and all questions will be answered by the Principal investigator, other 
physician investigator(s) who are part of the study or study coordinator.  Study enrolment will be initiated 
only after subjects have had all questions answered and have signed the informed consent form. 
 
 
Consent 
The consent process will be carried out as a joint effort among the study coordinator, PI or physician who 
is listed as an investigator on the study and the subject’s physician (if applicable).  If the subject is eligible 
for the study and has no exclusion criteria, the physician investigator and the clinical research coordinator 
will discuss with the subject about participation in the study and answer questions that the subject has 
about the study.  The PI or physician investigator will obtain informed consent.  Once all questions are 
satisfactorily addressed, the participant signs the consent form along with the investigator and a copy of 
the consent form is given to the participant.  
 
The potential participant will be address in a private room and the most current IRB-approved informed 
consent form is reviewed point by point.  All aspects of the clinical study will be explained to the subject, 
including but not limited to the nature of participation.  In addition, the subject is informed about the right 
to withdraw from the study at any time without any disadvantage and without having to provide a reason 
for this decision.  
 
Data Safety  

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Data and Safety Monitoring Plan (DSMP): 
Overall safety of research participants and adverse events will be continuously monitored by the Principal 
Investigator, study investigators and research staff.  All suspected adverse events should be reported 
immediately to the Principal Investigator.  Overall safety and study-wide adverse events will be reviewed 
by the local Data Safety and Monitoring Team consisting of the Principal Investigator, research staff and 
study investigators. Reportable Events will be submitted to the University of Pittsburgh Institutional 
Review Board per its reporting guidelines.   
 
Local DSMB: 
 
A local Data Safety and Monitoring Board (DSMB) will be responsible for meeting every 6 months to 
evaluate the progress of the research study, including assessment of data quality and subject recruitment.  
They will also monitor any suspected adverse events that are reported related to the devices and will 
assess to determine if the study design needs to be refined.  They will also review the procedures designed 
to protect the privacy of the research subjects and confidentiality of the research data.  The results of the 
DSMB meeting will be submitted to the IRB at the time of the annual renewal. 
 
Data Safety: 
All data entered into a local computer will be password protected. Care will be taken to ensure that the 
personal information in a subject’s medical record and research records will be kept private.  To protect 
subject privacy, the study staff will use a study number and initials rather than name on any photocopies 
of study records, and on any records that are sent outside of the local research institution(s) for review or 
testing. If information from this study is published in scientific journals or presented at scientific 
meetings, the subject’s name and other personal information will not be used.  Any breach in subject 
confidentiality will be reviewed at the DSMB and reported to the IRB per its guidelines. 
 
All data will be keyed into the web accessible RedCap database by the assigned staff.  Only study IDs 
will be used for data entry.  
 
This information is explained to the study participants in the informed consent as follows: If you agree to 
participate in the study, you can change your mind up until the end of the study.  When study researchers 
receive written instructions from you, they will destroy your records and all information that identifies 
you.  After the study ends, you will not be able to withdraw your records because the data storage facility 
will not know which records are yours.  
 
Data obtained as part of this study will be stored securely for secondary analyses.