Trial of Indomethacin in Chronic Pancreatitis

Study Overview
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Brief Summary
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The researchers are trying to find a way to slow down the progression of chronic pancreatitis (CP) and investigate the possibility of the long term treatment of this disease.

Official Title
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Phase 1/2 Trial of Indomethacin in Chronic Pancreatitis (The PAIR Trial)

Conditions
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Chronic Pancreatitis

Intervention / Treatment
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* Drug: Indomethacin
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any gender, age ≥ 18 years and < 60 years Diagnosed with chronic pancreatitis per American Pancreatic Association guidelines (pancreatic calcifications and/or Cambridge 3-4 changes on CT, MRI, and/or ERCP) Scheduled for an upper GI endoscopic procedure (EGD or EUS) for clinical or research) indications (not conflicting with current investigation). Able to provide written informed consent. Serum creatinine within normal laboratory range, as measured within 30 days of the baseline study endoscopy. For females of reproductive potential: willing to use highly effective contraception while taking study medication and for an additional 5 days after completing study medication. Exclusion Criteria: Diagnosed with acute pancreatitis requiring hospitalization within the 6 weeks prior to study enrollment. Habitual use of aspirin or non-steroidal anti-inflammatory medications (NSAIDs), defined as use more than once per week. Any use of aspirin or NSAIDs within 1 week of baseline study endoscopy procedure. Allergy to secretin, indomethacin or NSAIDs. History of known chronic renal insufficiency or cirrhosis. History of coronary artery disease, angina pectoris, myocardial infarction, cerebrovascular accident (stroke), or transient ischemic accident (TIA). History of peptic ulcer or gastrointestinal bleeding. Incarcerated. Found to have active GI ulceration at the time of baseline endoscopy. Hospitalized for acute pancreatitis while participating in this research protocol. Participants who are hospitalized for an episode of acute pancreatitis during study participation will be withdrawn from the study, and considered non-accrued.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Single Group Assignment
Interventional Model Description: Subjects will be assigned to receive IN or placebo according to a computer generated randomization list composed of randomized blocks of sizes of 2 or 4. Two separate sets of blocks will be created, one for subjects with alcoholic CP and the other for those with other causes of CP. Within each block, equal number of subjects will be assigned to IN and placebo. Separate sets of blocks will be provided for Mayo and Ohio State. The randomization lists will be computer generated by the study statistician (Dr Li), and kept in a secure computer file and paper study binder in the Mayo and Ohio State Research Pharmacies. No investigators or study personnel other than Dr Li will have knowledge of the randomization list. Dr Li will not participate in any aspect of subject recruitment, subject allocation, conduct of the study, or data ascertainment, but will perform data analysis.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral indomethacin 50 mg po BID<br>The study intervention is oral indomethacin. Indomethacin is an FDA approved, commonly prescribed NSAID. Commercially available indomethacin will be utilized in this study. One capsule orally BID for 28 days. Those in the indomethacin arm will receive indomethacin 50 mg BID. Participants will be advised not to make up missed doses. They will be advised to take a dose of study medication on the morning of their follow-up endoscopy, 2 hours prior to their scheduled procedure time, with a sip of water. At the time of follow-up endoscopy they will return any unused study medication. | Drug: Indomethacin<br>* 50 mg twice a day by mouth.<br>|
| Placebo Comparator: Placebo po BID<br>Participants in both study arms will receive study medication, one capsule orally BID for 28 days. Those in the placebo arm will receive placebo capsules BID. Participants will be advised not to make up missed doses. They will be advised to take a dose of study medication on the morning of their follow-up endoscopy, 2 hours prior to their scheduled procedure time, with a sip of water. At the time of follow-up endoscopy they will return any unused study medication. | Drug: Placebos<br>* Lactose capsules not containing active study drug will be taken twice a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in prostaglandin E2 (PGE2) concentrations | Mean change in PGE2 concentrations | Baseline, 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in pain | Measured using the self reported Brief Pain Inventory questionnaire | Baseline, 28 days | 
| Changes in quality of life | Measured using the self reported PROMIS Global quesionnaire | Baseline, 28 days |