The purpose of this study is to evaluate whether endoscopic ultrasound (EUS) only versus EUS + endoscopic retrograde cholangiopancreatography (ERCP) with pancreatic endotherapy reduces pain in the treatment of chronic pancreatitis with pancreatic duct obstruction.

This is a single center, pilot, sham-controlled clinical trial of ERCP with pancreatic endotherapy for pain secondary to chronic calcific pancreatitis with main pancreatic duct obstruction. Potential subjects will undergo a comprehensive baseline assessment including Quantitative Sensory Testing, to ensure enrollment criteria are met and baseline covariates are measured. Eligible subjects will complete a 14-day run-in period. If eligibility criteria persist, subjects will be randomized to diagnostic endoscopic ultrasound (EUS) + sham pancreatic endotherapy or diagnostic EUS + ERCP with pancreatic endotherapy as defined in the study protocol. Subjects will be followed by a blinded physician for the next 90 days, at which time the pilot trial outcomes will be measured. Regardless of outcomes, all subjects will be followed longitudinally for 12 months after randomization.

Inclusion Criteria

• Age ≥ 18 years
• Main pancreatic duct obstruction, defined by the presence of one or both of the following features:
• Main pancreatic duct calcification with upstream main duct dilation ≥6mm.
• Main pancreatic duct stricture, defined by the presence of main pancreatic duct narrowing with upstream main duct dilation ≥6mm.
• Baseline average abdominal pain score ≥4 during the run-in period, based on Ecological Momentary Assessment 11-point Numeric Rating Scale
• Ability to provide written, informed consent

Exclusion Criteria

• Symptoms attributable to a pancreatic pseudocyst or walled off necrosis
• Clinical suspicion of pancreatobiliary malignancy*
• Low probability of follow-up to complete study objectives
• Pregnancy or incarceration
• Medical comorbidities that contraindicate the performance of ERCP
• Previous pancreatic endotherapy
• Current Opioid Misuse Measure score ≥9
• Does not have access to a mobile phone * Pancreatobiliary malignancy

An Adverse Event form was used to document reportable adverse events (AEs) for this study, which included: 1. All non-serious adverse events related to abdominal pain in addition to all serious adverse events were reported through Day 30 2. All serious adverse events (SAEs) were reported through the end of study (12 months post randomization) 3. All acute pancreatitis events or pancreatitis-related pain events that occur were reported through end of study ((12 months post randomization).

Unblinded personnel reported AEs between randomization and Day 30. Blinded personnel reported AEs between Day 30 post randomization & up to the 90 day visit, then unblinded personnel reported any SAEs at Day 90 and afterwards.

Small sample size due to recruitment challenges

- It is difficult to recruit for the sham arm because endotherapy is widely utilized in clinical practice and advocated by expert consensus. Patients with painful chronic pancreatitis are disabled by their disease and often keen to try something even when risks are fixed and benefit unpredictable.

In addition to the participant and the investigator assessing outcomes, study coordinators involved in collecting outcomes data will be masked to the treatment assignment.