Metformin in Post Chronic Pancreatitis Diabetes Mellitus (MOOD)

Metformin in Post Chronic Pancreatitis Diabetes Mellitus: a Double-blind, Randomized, Placebo-controlled Trial

The goal of this clinical trial is to evaluate the efficacy and safety of metformin in treating patients with post chronic pancreatitis diabetes mellitus (PPDM-C). The main questions it aims to answer are:

• What is the efficacy of metformin in glycemic control in patients with PPDM-C?
• What is the incidence of adverse effects associated with metformin in patients with PPDM-C?

Participants will be randomly assigned to receive either metformin or a placebo to see if metformin provides significant glycemic control and to assess the safety profile of the treatment.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pancreatitis
• Intervention / Treatment: Drug: Metformin; Drug: Placebo

Detailed Description

Chronic pancreatitis (CP) is an irreversible chronic fibro-inflammatory disease caused by multiple factors. Patients often present with recurrent upper abdominal pain, dyspepsia, steatorrhea, and other symptoms. Typical imaging findings of CP include pancreatic duct calcification, ductal dilation, and parenchymal atrophy. As pancreatic fibrosis progresses, islet cells may also be damaged, leading to abnormal glucose metabolism or even diabetes mellitus (DM). Approximately 25-80% of CP patients develop DM which has been called post chronic pancreatitis diabetes mellitus (PPDM-C), with the prevalence increasing with the duration of CP. PPDM-C has garnered significant attention in the academic community due to its unique clinical manifestations and complications. However, there is currently no well-defined management strategy for PPDM-C.

The management of PPDM-C requires balancing pancreatic endocrine and exocrine functions, and developing individualized treatment strategies. Compared with T2DM patients, PPDM-C patients face greater difficulty in achieving optimal glycemic control. Currently, there is no standardized management for PPDM-C, with treatment protocol largely relying on clinical experience. Metformin is the most frequently used medication for PPDM patients (64.5%), and is typically the initial treatment. In PPDM-C patients, previous metformin use is associated with a survival benefit over those who have never used any antidiabetic drugs. However, there is lake of clinical trails specifically addressing PPDM-C to elucidate the the efficacy in glycemic control and safety of metformin.

• Study Type: Interventional
• Enrollment (Estimated): 58
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lianghao Hu, M.D.; Phone Number: +86-13817593520; Email: lianghao-hu@smmu.edu.cn
• Study Contact Backup: Name: Xiaoyu Zhou, M.D.; Phone Number: +86-17721292061; Email: xyzhou0116@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Changhai Hospital
      • Principal Investigator: Zhaoshen Li, M.D.
      • Contact: Lianghao Hu, M.D.; Phone Number: +86-13817593520; Email: lianghao-hu@smmu.edu.cn
      • Contact: Xiaoyu Zhou, M.D.; Phone Number: +86-17721292061; Email: xyzhou0116@163.com
      • Principal Investigator: Lianghao Hu, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18-65 years, any sex.
2. Patients diagnosed with chronic pancreatitis.
3. Diagnose diabetes at least 3 months after chronic pancreatitis diagnosis.
4. Never used any diabetes drug/glucose-lowering medication or had discontinued any glucose-lowering medications for at least 8 weeks prior to screening.
5. HbA1c criteria: 7.5%~9.0%.
6. BMI >18.5.
7. Provision of signed informed consent.

Exclusion Criteria:

1. Type 1 diabetes or secondary diabetes not caused by chronic pancreatitis (e.g. diabetes due to monogenic defects, cystic fibrosis, medications, autoimmune diseases, stress, or other factors).
2. Contraindications or history of intolerance or allergy to metformin.
3. Fasting C-peptide <0.3 nmol/L.
4. Acute episodes of chronic pancreatitis at enrollment or within 3 months prior to enrollment.
5. History of congestive heart failure (NYHA class 3 or greater), unstable angina, or other severe cardiovascular diseases.
6. History of cancer (except non-melanoma skin cancer) within 5 years prior to screening.
7. History of partial or total pancreatectomy.
8. History of or planning bariatric surgery.
9. Previous organ transplantation.
10. Treatment with oral or systemic glucocorticoids within 3 months prior to enrollment or plan to use during the study (inhaled steroids are permitted).
11. History of hemolytic anemia, chronic transfusion requirements, or other conditions rendering HbA1c results unreliable.
12. Other conditions requiring glucose-lowering medications, such as polycystic ovary syndrome.
13. Fasting blood glucose >11.1 mmol/L during screening, requiring immediate treatment as judged by the physician.
14. Sever psychiatric disorders or health conditions deemed unsuitable for clinical research participation.
15. Pregnancy or plans for pregnancy during the course of the study.
16. Any other condition considered by the investigator to be inappropriate for participation in the trial.

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: Metformin; Participants are administered metformin with an initial dose of 500 mg/day, which was incrementally increased by 500 mg/day each week until the maximum tolerated dose. The maximum dose of metformin is set at 2000 mg/day. After 2 weeks of administration, participants will undergo safety assessments, including complete blood count, urinalysis, liver function tests, and renal function tests. After attainment to a stable dose of metformin, participants will undergo follow-up assessments at 4 weeks, 8 weeks, and 12 weeks. The final evaluation of outcome measures will be completed at the 12-week follow-up.	Drug: Metformin; Participants are administered metformin with an initial dose of 500 mg/day, which was incrementally increased by 500 mg/day each week until the maximum tolerated dose. The maximum dose of metformin is set at 2000 mg/day.
Placebo Comparator: Placebo; Participants are administered a placebo, starting with one tablet per day, followed by an incremental increase of one tablet per week. In the absence of adverse reactions, the dosage is escalated up to a maximum of four tablets per day. After 2 weeks of administration, participants will undergo safety assessments, including complete blood count, urinalysis, liver function tests, and renal function tests. After attainment to a stable dose, participants will undergo follow-up assessments at 4 weeks, 8 weeks, and 12 weeks. The final evaluation of outcome measures will be completed at the 12-week follow-up.	Drug: Placebo; Participants are administered a placebo, starting with one tablet per day, followed by an incremental increase of one tablet per week. In the absence of adverse reactions, the dosage is escalated up to a maximum of four tablets per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in glycosylated hemoglobin (HbA1c)	The change in the value of glycosylated hemoglobin (HbA1c) collected at Week 12 (after the attainment of a stable does) relative to baseline.	12 weeks after the attainment of a stable dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients with HbA1c below 6.5% at Week 12	At the Week 12 after the attainment of a stable does, the proportions of patients with glycosylated hemoglobin (HbA1c) levels exceeding 6.5% are assessed.	12 weeks after the attainment of a stable dose
The proportion of patients with HbA1c below 7% at Week 12	At the Week 12 after the attainment of a stable does, the proportions of patients with glycosylated hemoglobin (HbA1c) levels exceeding 7% are assessed.	12 weeks after the attainment of a stable dose
The proportion of patients with HbA1c below 7.5% at Week 12	At the Week 12 after the attainment of a stable does, the proportions of patients with glycosylated hemoglobin (HbA1c) levels exceeding 7.5% are assessed.	12 weeks after the attainment of a stable dose
The incidence of adverse events	Adverse events include hypoglycemia, diabetic ketoacidosis, hyperglycemic hyperosmolar state, acute pancreatitis and gastrointestinal symptoms (nausea, vomiting, diarrhea, etc.).	12 weeks after the attainment of a stable dose
Blood glucose profile characteristics	Blood glucose profile from continuous glucose monitoring system (CGMS) (unit: mmol/L or mg/dL).	12 weeks after the attainment of a stable dose
Exploratory objectives: pancreatic exocrine function	Pancreatic exocrine function is evaluated by fecal elastase-1 test.	12 weeks after the attainment of a stable dose
Exploratory objectives: scores of quality of life	Quality of life scores for patients with chronic pancreatitis are obtained using SF-36 (36-Item Short Form Health Survey) which contains 8 dimensions scored from 0 to 100 (standardized converted scores). The higher score means better function.	12 weeks after the attainment of a stable dose
Exploratory objectives: pancreatic and gut hormones	Levels of specific pancreatic hormones (C-peptide, insulin, glucagon, etc.) and gut hormones (ghrelin, gastric inhibitory peptide, glucagon like peptide-1, etc.) measured in venous blood (unit: mmol/L or mg/dL).	Baseline

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Investigators: Principal Investigator: Lianghao Hu, M.D., Changhai Hospital; Study Chair: Zhaoshen Li, M.D., Changhai Hospital

Publications and helpful links

General Publications

• Vege SS, Chari ST. Chronic Pancreatitis. N Engl J Med. 2022 Mar 3;386(9):869-878. doi: 10.1056/NEJMcp1809396. No abstract available.
• Cho J, Petrov MS. Pancreatitis, Pancreatic Cancer, and Their Metabolic Sequelae: Projected Burden to 2050. Clin Transl Gastroenterol. 2020 Nov;11(11):e00251. doi: 10.14309/ctg.0000000000000251.
• Petrov MS. Diabetes of the exocrine pancreas: American Diabetes Association-compliant lexicon. Pancreatology. 2017 Jul-Aug;17(4):523-526. doi: 10.1016/j.pan.2017.06.007. Epub 2017 Jun 19.
• Beyer G, Habtezion A, Werner J, Lerch MM, Mayerle J. Chronic pancreatitis. Lancet. 2020 Aug 15;396(10249):499-512. doi: 10.1016/S0140-6736(20)31318-0.
• Pan J, Xin L, Wang D, Liao Z, Lin JH, Li BR, Du TT, Ye B, Zou WB, Chen H, Ji JT, Zheng ZH, Hu LH, Li ZS. Risk Factors for Diabetes Mellitus in Chronic Pancreatitis: A Cohort of 2,011 Patients. Medicine (Baltimore). 2016 Apr;95(14):e3251. doi: 10.1097/MD.0000000000003251.
• Zhu X, Liu D, Wei Q, Lin H, Zhi M, Chen Y, Qi L, Waldron RT, Lugea A, Pandol SJ, Li L. New-Onset Diabetes Mellitus After Chronic Pancreatitis Diagnosis: A Systematic Review and Meta-analysis. Pancreas. 2019 Aug;48(7):868-875. doi: 10.1097/MPA.0000000000001359.
• Olesen SS, Viggers R, Drewes AM, Vestergaard P, Jensen MH. Risk of Major Adverse Cardiovascular Events, Severe Hypoglycemia, and All-Cause Mortality in Postpancreatitis Diabetes Mellitus Versus Type 2 Diabetes: A Nationwide Population-Based Cohort Study. Diabetes Care. 2022 Jun 2;45(6):1326-1334. doi: 10.2337/dc21-2531.
• Viggers R, Jensen MH, Laursen HVB, Drewes AM, Vestergaard P, Olesen SS. Glucose-Lowering Therapy in Patients With Postpancreatitis Diabetes Mellitus: A Nationwide Population-Based Cohort Study. Diabetes Care. 2021 Sep;44(9):2045-2052. doi: 10.2337/dc21-0333. Epub 2021 Aug 6.
• Cho J, Scragg R, Pandol SJ, Goodarzi MO, Petrov MS. Antidiabetic Medications and Mortality Risk in Individuals With Pancreatic Cancer-Related Diabetes and Postpancreatitis Diabetes: A Nationwide Cohort Study. Diabetes Care. 2019 Sep;42(9):1675-1683. doi: 10.2337/dc19-0145. Epub 2019 Jun 21.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: April 7, 2025
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 22, 2025

Study Record Updates

• Last Update Posted (Actual): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 16, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Metabolic Diseases; Digestive System Diseases; Glucose Metabolism Disorders; Pancreatic Diseases; Pancreatitis; Pancreatitis, Chronic; Diabetes Mellitus; Physiological Effects of Drugs; Hypoglycemic Agents; Metformin
• Other Study ID Numbers: MOOD202501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No