Metformin in Post Chronic Pancreatitis Diabetes Mellitus

NCT ID: NCT06937294

Last Updated: 2025-05-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

58 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-28

Study Completion Date

2026-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Chronic Pancreatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients will be randomized to the experimental group (metformin) or the control group (placebo).
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
This study is a double-blind trail. Participants, investigators, care providers and outcomes assessors are blinded to the group allocations. Investigators and care providers provide guidance on drug use and lifestyle. Outcomes assessors are responsible for the follow-up of the patients. A study coordinator, who is not blinded to the group allocations, is appointed to oversee the coordination of the study and the maintenance of the blinding procedures. The study coordinator do not be allowed to communicate with others (participants, investigators, care providers and outcomes assessors) regarding the group allocations and clinical conditions of the participants. In the event of a serious adverse event, the blinding could be broken by contacting the study coordinator for safety considerations, and the reasons for unblinding were documented in detail.

Study Groups

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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.

Group Type EXPERIMENTAL

Metformin

Intervention Type DRUG

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

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Changhai Hospital

OTHER

Sponsor Role lead

Responsible Party

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Zhaoshen Li

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Zhaoshen Li, M.D.

Role: STUDY_CHAIR

Changhai Hospital

Lianghao Hu, M.D.

Role: PRINCIPAL_INVESTIGATOR

Changhai Hospital

Locations

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Changhai Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Lianghao Hu, M.D.

Role: CONTACT

+86-13817593520

Xiaoyu Zhou, M.D.

Role: CONTACT

+86-17721292061

Facility Contacts

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Lianghao Hu, M.D.

Role: primary

+86-13817593520

Xiaoyu Zhou, M.D.

Role: backup

+86-17721292061

References

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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.

Reference Type RESULT
PMID: 33259158 (View on PubMed)

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.

Reference Type RESULT
PMID: 28655595 (View on PubMed)

Vege SS, Chari ST. Chronic Pancreatitis. N Engl J Med. 2022 Mar 3;386(9):869-878. doi: 10.1056/NEJMcp1809396. No abstract available.

Reference Type RESULT
PMID: 35235728 (View on PubMed)

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.

Reference Type RESULT
PMID: 32798493 (View on PubMed)

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.

Reference Type RESULT
PMID: 27057870 (View on PubMed)

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.

Reference Type RESULT
PMID: 31268977 (View on PubMed)

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.

Reference Type RESULT
PMID: 35312752 (View on PubMed)

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.

Reference Type RESULT
PMID: 34362812 (View on PubMed)

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.

Reference Type RESULT
PMID: 31227582 (View on PubMed)

Other Identifiers

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MOOD202501

Identifier Type: -

Identifier Source: org_study_id

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