Trial of Indomethacin in Chronic Pancreatitis

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Pancreatitis
• Intervention / Treatment: Drug: Indomethacin; Procedure: Endoscopy for Pancreatic Function Testing; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Any gender, age ≥ 18 years and < 60 years
2. Diagnosed with chronic pancreatitis per American Pancreatic Association guidelines (pancreatic calcifications and/or Cambridge 3-4 changes on CT, MRI, and/or ERCP)
3. Scheduled for an upper GI endoscopic procedure (EGD or EUS) for clinical or research) indications (not conflicting with current investigation).
4. Able to provide written informed consent.
5. Serum creatinine within normal laboratory range, as measured within 30 days of the baseline study endoscopy.
6. 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:

1. Diagnosed with acute pancreatitis requiring hospitalization within the 6 weeks prior to study enrollment.
2. Habitual use of aspirin or non-steroidal anti-inflammatory medications (NSAIDs), defined as use more than once per week.
3. Any use of aspirin or NSAIDs within 1 week of baseline study endoscopy procedure.
4. Allergy to secretin, indomethacin or NSAIDs.
5. History of known chronic renal insufficiency or cirrhosis.
6. History of coronary artery disease, angina pectoris, myocardial infarction, cerebrovascular accident (stroke), or transient ischemic accident (TIA).
7. History of peptic ulcer or gastrointestinal bleeding.
8. Incarcerated.
9. Found to have active GI ulceration at the time of baseline endoscopy.
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Indomethacin; The study intervention is oral indomethacin. Indomethacin is an FDA approved, commonly prescribed non-steroidal anti-inflammatory drug (NSAID). Commercially available indomethacin will be utilized in this study. Subjects randomized to the indomethacin arm will take one capsule of 50 mg of Indomethacin orally twice a day for 28 days. 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 medications.	Drug: Indomethacin; One capsule of 50 mg of indomethacin will be taken orally twice a day for a total of 28 days.; Procedure: Endoscopy for Pancreatic Function Testing; All subjects in the study (regardless of which treatment arm they are randomized to) will undergo an upper endoscopy during which they will receive an endoscopic pancreatic function test. An upper endoscopy will be performed during the baseline visit and at the follow-up visit at day 28 of the treatment (2 endoscopies total per each subject). Specifically, during the upper endoscopy, secretin will be administered intravenously at a weight-based dose of 0.2 mcg/kg over 1 minute. Fluid will be aspirated from the duodenum through the endoscope from 0-10 minutes and 10-20 minutes following secretin administration. The collected fluid will then be sent to the laboratory for analysis.
Placebo Comparator: Placebo; Participants in both study arms will receive study medication, one capsule orally twice a day for 28 days. Those in the placebo arm will take placebo capsules (one capsule) twice a day for a total of 28 days. 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.	Procedure: Endoscopy for Pancreatic Function Testing; All subjects in the study (regardless of which treatment arm they are randomized to) will undergo an upper endoscopy during which they will receive an endoscopic pancreatic function test. An upper endoscopy will be performed during the baseline visit and at the follow-up visit at day 28 of the treatment (2 endoscopies total per each subject). Specifically, during the upper endoscopy, secretin will be administered intravenously at a weight-based dose of 0.2 mcg/kg over 1 minute. Fluid will be aspirated from the duodenum through the endoscope from 0-10 minutes and 10-20 minutes following secretin administration. The collected fluid will then be sent to the laboratory for analysis.; Drug: Placebo; One capsule of lactose not containing active study drug will be taken orally twice a day for a total of 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Prostaglandin E2 (PGE2) Concentrations	Mean change in PGE2 concentrations in pancreas fluid before and after intervention	Baseline, 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Pain Interference Score	Measured using the self reported Brief Pain Inventory questionnaire. The pain interference subscale includes 7 items which each utilize a 11-point scale from 0-10, with 10 representing the worst outcome (highest level of pain). The scores from the 7 items are summed to create a total score. Thus, the total score can range from 0-70. The total pain interference score at baseline was then subtracted from the total pain interference score at 28 days to calculate the change in pain interference score.	Baseline, 28 days
Change in Quality of Life (Mental Health)	Measured using the self reported PROMIS-10 instrument. The PROMIS-10 instrument includes 4 items for mental health, which each have 1-5 scale, with 5 representing the worst outcome. T-scores are then calculated from the raw scores. A mean T-score of 50 represents average health with a standard deviation of 10. Higher scores denote a worse outcome. The mean T-score at baseline was then subtracted from the mean T-score at 28 days to derive the change in mental quality of life..	Baseline, 28 days
Change in Pain Composite Score	Assessed using the Brief Pain Inventory (BPI) scale. The pain composite score includes 4 questions from the BPI, each of which is scored on a 0-10 scale with 10 representing the worst outcome (highest level of pain) and 0 representing the best outcome (no pain). The 4 questions assess 1) worst pain, 2) least pain, 3) average pain, and 4) current pain. The mean score of the responses to these 4 questions is calculated to derive the pain composite score. Thus, the pain composite score will also range from 0-10. The mean pain composite score at baseline was then subtracted from the mean pain composite score at 28 days to calculate the change in pain composite score.	Baseline, 28 days
Change in Quality of Life (Physical Health)	Quality of life measured using the self reported PROMIS-10 instrument. The PROMIS-10 instrument includes 4 items for physical health, which each have a 1-5 scale, with 5 representing the worst outcome. T-scores are then calculated from the raw scores. A T-score of 50 indicates the population mean with a standard deviation of 10. Higher T-scores represent worse outcomes. The mean T-score at baseline was then subtracted from the mean T-score at 28 days to derive the change in physical quality of life.	Baseline, 28 days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Santhi Vege, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2020
• Primary Completion (Actual): April 24, 2023
• Study Completion (Actual): April 24, 2023

Study Registration Dates

• First Submitted: December 17, 2019
• First Submitted That Met QC Criteria: December 18, 2019
• First Posted (Actual): December 20, 2019

Study Record Updates

• Last Update Posted (Actual): September 4, 2024
• Last Update Submitted That Met QC Criteria: August 8, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Pancreatic Diseases; Chronic Disease; Pancreatitis; Pancreatitis, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Reproductive Control Agents; Gout Suppressants; Tocolytic Agents; Indomethacin
• Other Study ID Numbers: 18-008193; R21DK117212 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No