Pancreatic Endotherapy for Refractory Chronic Pancreatitis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Pancreatic Endotherapy for Refractory Chronic Pancreatitis

Conditions
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Pancreatic Duct Stone, Pancreatic Duct Stricture, Pancreatic Duct Dilatation

Intervention / Treatment
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* Procedure: EUS + SHAM
* Procedure: EUS + Pancreatic Endotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: EUS + SHAM<br>All subjects will undergo anesthesia administered sedation and endoscopic ultrasound (EUS). The endoscopist will assess the pancreas for parenchymal and ductal features of chronic pancreatitis and confirm the absence of exclusion criteria (such as the presence of an occult pancreatobiliary malignancy). | Procedure: EUS + SHAM<br>* Endoscopic Ultrasound<br>|
| Experimental: EUS + Pancreatic Endotherapy<br>If randomized to ERCP with pancreatic endotherapy, the endoscopist will proceed with this intervention immediately following the completion of EUS and treatment allocation (during the same anesthesia). Pancreatic endotherapy may include any or all of the following maneuvers: pancreatic endoscopic sphincterotomy, stricture dilation using a bougie or hydrostatic balloon catheter, pancreatic stone extraction with or without mechanical or electrohydraulic lithotripsy, extracorporeal shock wave lithotripsy, and stent placement. Overall technical success will be defined by the ability to insert at least one pancreatic stent across the dominant main pancreatic duct obstruction. Technical success for pancreatic stone treatment will be defined by the ability to remove all fluoroscopically visible main pancreatic duct stones. | Procedure: EUS + Pancreatic Endotherapy<br>* Pancreatic endotherapy may include any or all of the following maneuvers: pancreatic endoscopic sphincterotomy, stricture dilation using a bougie or hydrostatic balloon catheter, pancreatic stone extraction with or without mechanical or electrohydraulic lithotripsy, extracorporeal shock wave lithotripsy, and stent placement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average daily pain: Numeric Rating Scale (NRS) | The average daily pain from the electronic diaries during the 14-day period preceding the 90-day assessment, compared to the average daily pain reported during the 14-day run-in. Clinical improvement will be defined by the change in the average pain score between these two intervals, and without the need for increased opioids or additional interventions/procedures. The investigators will employ the standardized 11-point Numeric Rating Scale (NRS) to capture average daily pain with the empirically-supported anchors of 0=No Pain and 10=Worst Pain Imaginable. | Day -14 to Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in pain severity and functional impairment | At 90-days, change from baseline in functional impairment due to pain will be examined. The instrument used is Brief Pain Inventory (BPI), Measures pain at its worst, least, average, and at time of evaluation Measures patient perception of effectiveness of current pain medications Measures functional impairment due to pain | Baseline to Day 90 | 
| Quality of Life: Using the PROMIS 29 instrument | Using the PROMIS 29 instrument, quality of life will be assessed through this questionnaire evaluating anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, ability to participate in social roles and activities, and a single pain intensity item. | Baseline to Day 90 | 
| Opioid Misuse | Using the instrument titled Current Opioid Misuse Measure (COMM), this will be evaluated by patient self-reported measures of risk for aberrant medication-related behavior in patients prescribed opioids for chronic pain. | Baseline to Day 90 | 
| Pain Catastrophizing | The instrument titled Pain Catastrophizing Scale (PCS) used to assess pain catastrophizing will do the following: Measure of negative cognitive-set brought to bear during painful experiences Predict functional impairment due to pain and pain-related depression | Baseline to Day 90 | 
| Mechanical pain threshold | Using Quantitative Sensory Testing, assess the mechanical pain threshold using the IITC Life Sciences Digital Anesthesiometer applied to the distal phalange of the digiti minimi of the left hand (increased at rate of 10grams/sec; pressure recorded in grams). | Baseline to Day 90 | 
| Pain tolerance: Quantitative Sensory Testing | Using Quantitative Sensory Testing, assess thermal pain tolerance using 5 trials of cutaneous heat stimuli via the thermode of the Medoc TSA-II Neurosensory Analyzer. | Baseline to Day 90 | 
| Pain wind up | Using Quantitative Sensory Testing, assess thermal wind-up pain (3 trials) with the thermode delivering 20 brief suprathreshold thermal pulses at the rate of 1 pulse per 1.5 secs thereby selectively stimulating C-fibers (during the 3 trials of 30sec of repeated heat stimulation, subjects will indicate their level of pain severity using a dynamic visual analogue scale). | Baseline to Day 90 | 
| Conditioned pain modulation | Using Quantitative Sensory Testing, assess conditioned pain modulation (3 trials) using mechanical pain thresholds assessed via the IITC Life Sciences Digital Anesthesiometer applied to the right trapezus (increased at rate of 10grams/sec; pressure recorded in grams) with and without simultaneous stimulation via the ATS thermode. | Baseline to Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreas, pancreatic duct, ductal stone, duct stricture, ERCP, pancreatic duct obstruction, duct calcification