Trial of Indomethacin in Chronic Pancreatitis

NCT04207060 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 18-008193R21DK117212
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Chronic Pancreatitis

Outcome Measures

Primary Outcomes (1)

• Change in Prostaglandin E2 (PGE2) Concentrations

  Mean change in PGE2 concentrations in pancreas fluid before and after intervention

  Baseline, 28 days

Secondary Outcomes (4)

• Changes in Pain Interference Score

  Baseline, 28 days

• Change in Quality of Life (Mental Health)

  Baseline, 28 days

• Change in Pain Composite Score

  Baseline, 28 days

• Change in Quality of Life (Physical Health)

  Baseline, 28 days

Study Arms (2)

Indomethacin

EXPERIMENTAL

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; Procedure: Endoscopy for Pancreatic Function Testing

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Procedure: Endoscopy for Pancreatic Function Testing

Interventions

Indomethacin DRUG

One capsule of 50 mg of indomethacin will be taken orally twice a day for a total of 28 days.

Indomethacin

Placebo DRUG

One capsule of lactose not containing active study drug will be taken orally twice a day for a total of 28 days.

Placebo

Endoscopy for Pancreatic Function Testing PROCEDURE

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.

Indomethacin; Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Han S, Vege SS, Hart PA, Saloman JL, Xu J, Li L, Cruz-Monserrate Z, Palermo TM, Hill R, Hao W, Yadav D, Topazian M, Conwell DL. Oral Indomethacin for Chronic Pancreatitis: Results From the PAIR Randomized Placebo-Controlled Trial. Clin Transl Gastroenterol. 2025 Sep 1;16(9):e00888. doi: 10.14309/ctg.0000000000000888.

  PMID: 40622408 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Pancreatitis, Chronic

Interventions

Indomethacin; Endoscopy

Condition Hierarchy (Ancestors)

Pancreatitis; Pancreatic Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative

Limitations and Caveats

Limitations include the short treatment period as participants received the study medication for only 28 days, which may be too short to detect a significant biochemical change in a chronic disease such as chronic pancreatitis. Additionally, as this was a Phase 1/2 study, the only dose chosen for the intervention, indomethacin, was 50 mg BID, which may not represent an effective dose to modify chronic pancreatitis. Furthermore, the short follow-up period limits ascertaining long-term effects.

Results Point of Contact

• Title: Dr. Santhi Swaroop Vege
• Organization: Mayo Clinic

vege.santhi@mayo.edu

(507) 266-6931

Study Officials

• Santhi Vege, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding: Study medication will be labelled "indomethacin 50 mg or placebo capsule" with the subject's name, hospital or clinic number, study IRB number, and subject number. Placebo and indomethacin capsules will be identical in appearance. The investigators, study coordinator, and clinical caregivers will remain blinded to subject allocation throughout the data ascertainment and data entry phase of the study. The success of blinding will be evaluated by asking the investigator, the study coordinator, and the subject the following question during each telephone follow-up visit: "Which treatment group is this subject/were you assigned to: placebo, active drug, or unsure?"
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Subjects will be assigned to receive indomethacin or placebo according to a computer generated randomization list composed of randomized blocks of sizes of 2 or 4. Within each block, equal number of subjects will be assigned to indomethacin and placebo. Separate sets of blocks will be provided for Mayo Clinic 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.

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 20, 2019
• Study Start: July 15, 2020
• Primary Completion: April 24, 2023
• Study Completion: April 24, 2023
• Last Updated: September 4, 2024
• Results First Posted: September 4, 2024

Record last verified: 2024-08

Locations

US (2)