Trial of Indomethacin in Chronic Pancreatitis

Sponsor

Mayo Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT04207060

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Locations

Arms

31.5

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Pancreatitis	Drug: Indomethacin Drug: Placebos	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Intervention 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.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 (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

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 IN 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?"

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 15, 2020

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral indomethacin 50 mg po BID 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 50 mg twice a day by mouth.
Placebo Comparator: Placebo po BID 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 Lactose capsules not containing active study drug will be taken twice a day.

Arm

Intervention/Treatment

Experimental: Oral indomethacin 50 mg po BID

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

50 mg twice a day by mouth.

Placebo Comparator: Placebo po BID

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

Lactose capsules not containing active study drug will be taken twice a day.

Outcome Measures

Primary Outcome Measures

Change in prostaglandin E2 (PGE2) concentrations [Baseline, 28 days]
Mean change in PGE2 concentrations

Secondary Outcome Measures

Changes in pain [Baseline, 28 days]
Measured using the self reported Brief Pain Inventory questionnaire
Changes in quality of life [Baseline, 28 days]
Measured using the self reported PROMIS Global quesionnaire

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905
2	Ohio State University	Columbus	Ohio	United States	43210

Sponsors and Collaborators

Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

Principal Investigator: Santhi Vege, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Mayo Clinic Clinical Trials

Publications

None provided.

Responsible Party:

Santhi Swaroop Vege, Principal Investigator, Mayo Clinic

ClinicalTrials.gov Identifier:

NCT04207060

Other Study ID Numbers:

18-008193
R21DK117212

First Posted:

Dec 20, 2019

Last Update Posted:

May 3, 2022

Last Verified:

May 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Pancreatitis

Pancreatitis, Chronic

Indomethacin

Study Results

No Results Posted as of May 3, 2022