GLP-1 Agonists for Prevention of Recurrent Hypertriglyceridemic Acute Pancreatitis

Phase 4Not Yet RecruitingNCT07617155

Peking Union Medical College Hospital396 enrolled

Overview

Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is associated with a high risk of recurrence despite standard lipid-lowering therapy and lifestyle modification. The goal of this clinical trial is to evaluate whether GLP-1 receptor agonist therapy can reduce the recurrence of HTG-AP in adults with a history of HTG-AP and hypertriglyceridemia. The main questions this study aims to answer are: * Whether GLP-1 receptor agonist therapy reduces the recurrence rate of HTG-AP. * Whether GLP-1 receptor agonist therapy improves triglyceride control, body weight, and metabolic parameters. * Whether GLP-1 receptor agonist therapy is safe and well tolerated in this patient population. Researchers will compare GLP-1 receptor agonist therapy plus standard care with standard care alone to determine whether GLP-1 receptor agonist therapy provides additional benefit in preventing recurrent HTG-AP. Participants will: * Receive either GLP-1 receptor agonist therapy plus standard care or standard care alone. * Undergo regular clinical follow-up visits and laboratory assessments. * Receive monitoring of triglyceride levels, recurrence events, metabolic outcomes, and adverse events during the study period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

396

Conditions

Hypertriglyceridemia Induced Acute Pancreatitis Recurrent Acute Pancreatitis

Interventions

SemaglutideDRUG

Semaglutide is administered as a once-weekly subcutaneous injection for 18 months. Treatment is initiated at 0.25 mg once weekly for the first 4 weeks and escalated to 0.5 mg once weekly thereafter to improve tolerability.

Placebo (Normal Saline)DRUG

Placebo consists of normal saline administered as a once-weekly subcutaneous injection following the same administration schedule as semaglutide for 18 months. Participants receive 0.25 mg-equivalent injection volume once weekly for the first 4 weeks followed by 0.5 mg-equivalent injection volume once weekly thereafter.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria * Age ≥ 18 years old * Previous diagnosis of index HTG-AP (defined as AP with serum TG \>1000 mg/dL or a serum TG level of 500-1000 mg/dL accompanied by chylous serum)36-38 * Having HTG as the exclusive cause of AP * Time from discharge of index HTG-AP to recruitment between 4 weeks to 3 months, without AP-related symptoms between discharge and recruitment * Expression of the willingness to comply with lifestyle modification during the study period. * Clinically stable at the time of inclusion * The ability to understand the trial and completing it, as evaluated by the investigators. * Patients who may get pregnant should ensure using contraceptives for 20 months after inclusion Exclusion Criteria * History of malignancy in past 5 years * History of hypothyroidism, nephrotic syndrome, Cushing's syndrome or AIDS * History of chronic pancreatitis or pancreatic neoplasm * History of severe cardiovascular and pulmonary diseases, such as heart failure, coronary heart disease and chronic obstructive pulmonary disease. * Severe renal deficiency (glomerular filtration rate \< 30 ml/min) * Severe hepatic deficiency (Child-Pugh Class B or C) * Previous pancreatic surgery * Recurrent AP due to pancreatic diverticulum * Recurrent AP due to known genetic mutations (eg. CFTR) * Personal or family history of medullary thyroid carcinoma (MTC) * Current or prior diagnosis or suspected diagnosis of multiple endocrine neoplasia type 2 (MEN2) * Serious hypersensitivity reaction to semaglutide or any of the excipients in the investigational drug or placebo * Pregnancy * Breast-feeding

Outcomes

Primary Outcomes

Proportion of participants with recurrent hypertriglyceridemia-induced acute pancreatitis

Recurrent hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is defined as an episode of acute pancreatitis occurring at least 1 month after complete symptom resolution from the index episode, with serum triglycerides \>1000 mg/dL or triglycerides 500-1000 mg/dL accompanied by chylous serum and no other identifiable cause of acute pancreatitis.

Time frame: Within 18 months after randomization

Secondary Outcomes

Number of recurrent hypertriglyceridemia-induced acute pancreatitis episodes

Total number of recurrent HTG-AP episodes experienced by each participant during follow-up.

Time frame: 18 months after randomization

Change in fasting serum triglyceride level

Change in fasting serum triglyceride concentration from baseline.