Trial of Indomethacin in Chronic Pancreatitis

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

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04207060

Enrollment

Registered

2019-12-20

Start date

2020-07-15

Completion date

2023-04-24

Last updated

2024-09-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Pancreatitis

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.

Interventions

DRUGIndomethacin

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

DRUGPlacebo

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

PROCEDUREEndoscopy 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, 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 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?

Intervention model description

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.

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Changes in Pain Interference Score	Baseline, 28 days	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.
Change in Quality of Life (Mental Health)	Baseline, 28 days	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..
Change in Pain Composite Score	Baseline, 28 days	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.
Change in Quality of Life (Physical Health)	Baseline, 28 days	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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. Indomethacin: One capsule of 50 mg of indomethacin will be taken orally twice a day for a total of 28 days. 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.	13
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. Placebo: One capsule of lactose not containing active study drug will be taken orally twice a day for a total of 28 days. 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.	14
Total	27

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	2	0

Baseline characteristics

Characteristic	Indomethacin	Placebo	Total
Age, Continuous	56.2 years STANDARD_DEVIATION 11.6	51.1 years STANDARD_DEVIATION 11.4	53.5 years STANDARD_DEVIATION 11.6
Baseline PGE2 Level	812.4 pg/ml STANDARD_DEVIATION 581.4	991.6 pg/ml STANDARD_DEVIATION 1000.3	905.3 pg/ml STANDARD_DEVIATION 790.9
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	2 Participants	8 Participants	10 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) White	10 Participants	6 Participants	16 Participants
Region of Enrollment United States	13 participants	14 participants	27 participants
Sex: Female, Male Female	8 Participants	6 Participants	14 Participants
Sex: Female, Male Male	5 Participants	8 Participants	13 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 13	0 / 14
other Total, other adverse events	4 / 13	4 / 14
serious Total, serious adverse events	0 / 13	0 / 14

Arm	Measure	Value (MEAN)	Dispersion
Indomethacin	Changes in Pain Interference Score	-2.9 score on a scale	Standard Deviation 3.6
Placebo	Changes in Pain Interference Score	-0.4 score on a scale	Standard Deviation 1.3

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026