Metformin in Post Chronic Pancreatitis Diabetes Mellitus

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Change from baseline in glycosylated hemoglobin (HbA1c) [Срок оценки: 12 weeks after the attainment of a stable dose]

Вторичные конечные точки (8)

• The proportion of patients with HbA1c below 6.5% at Week 12 [Срок оценки: 12 weeks after the attainment of a stable dose]
• The proportion of patients with HbA1c below 7% at Week 12 [Срок оценки: 12 weeks after the attainment of a stable dose]
• The proportion of patients with HbA1c below 7.5% at Week 12 [Срок оценки: 12 weeks after the attainment of a stable dose]
• The incidence of adverse events [Срок оценки: 12 weeks after the attainment of a stable dose]
• Blood glucose profile characteristics [Срок оценки: 12 weeks after the attainment of a stable dose]
• Exploratory objectives: pancreatic and gut hormones [Срок оценки: Baseline]
• Exploratory objectives: pancreatic exocrine function [Срок оценки: 12 weeks after the attainment of a stable dose]
• Exploratory objectives: scores of quality of life [Срок оценки: 12 weeks after the attainment of a stable dose]

Критерии участия

Критерии включения

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

Критерии исключения

• 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).
• Contraindications or history of intolerance or allergy to metformin.
• Fasting C-peptide <0.3 nmol/L.
• Acute episodes of chronic pancreatitis at enrollment or within 3 months prior to enrollment.
• History of congestive heart failure (NYHA class 3 or greater), unstable angina, or other severe cardiovascular diseases.
• History of cancer (except non-melanoma skin cancer) within 5 years prior to screening.
• History of partial or total pancreatectomy.
• History of or planning bariatric surgery.
• Previous organ transplantation.
• Treatment with oral or systemic glucocorticoids within 3 months prior to enrollment or plan to use during the study (inhaled steroids are permitted).
• History of hemolytic anemia, chronic transfusion requirements, or other conditions rendering HbA1c results unreliable.
• Other conditions requiring glucose-lowering medications, such as polycystic ovary syndrome.
• Fasting blood glucose >11.1 mmol/L during screening, requiring immediate treatment as judged by the physician.
• Sever psychiatric disorders or health conditions deemed unsuitable for clinical research participation.
• Pregnancy or plans for pregnancy during the course of the study.
• Any other condition considered by the investigator to be inappropriate for participation in the trial.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Changhai Hospital — Шанхай

Публикации

• 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. PMID 33259158
• 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. PMID 28655595
• Vege SS, Chari ST. Chronic Pancreatitis. N Engl J Med. 2022 Mar 3;386(9):869-878. doi: 10.1056/NEJMcp1809396. No abstract available. PMID 35235728
• 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. PMID 32798493
• 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. PMID 27057870
• 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. PMID 31268977
• 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. PMID 35312752
• 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. PMID 34362812

Идентификаторы

NCT: NCT06937294 · MOOD202501

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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