GLP-1 Agonists for Prevention of Recurrent Hypertriglyceridemic Acute Pancreatitis

Official title

Effects of GLP-1 Agonists on Prevention of HTG-Induced Acute Pancreatitis Recurrence: Protocol for a Randomized Clinical Trial

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.

Interventions

• Drug Semaglutide
  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.
• Drug Placebo (Normal Saline)
  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.

Primary outcome measures

• Proportion of participants with recurrent hypertriglyceridemia-induced acute pancreatitis [Time frame: Within 18 months after randomization]

Secondary outcome measures (12)

• Number of recurrent hypertriglyceridemia-induced acute pancreatitis episodes [Time frame: 18 months after randomization]
• Change in fasting serum triglyceride level [Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months]
• Change in PAN-PROMISE score [Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months]
• Change in lipid profile parameters [Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months]
• Change in glycemic parameters [Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months]
• Change in anthropometric measures [Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months]
• Change in smoking [Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months]
• Change in alcohol consumption [Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months]
• MRI assessment of hepatic and pancreatic fat infiltration and pancreatic volume [Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months]
• Incidence of metabolic and pancreatic complications [Time frame: Within 18 months after randomization]
• Incidence of chronic pancreatitis [Time frame: 18 months after randomization]
• Change in health-related quality of life [Time frame: Baseline and 18 months after randomization]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

China · 1 center

• Peking Union Medical College Hospital — Beijing

Publications

• Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011 Dec;20(10):1727-36. doi: 10.1007/s11136-011-9903-x. Epub 2011 Apr 9. PMID 21479777
• de-Madaria E, Sanchez-Marin C, Carrillo I, Vege SS, Chooklin S, Bilyak A, Mejuto R, Mauriz V, Hegyi P, Marta K, Kamal A, Lauret-Brana E, Barbu ST, Nunes V, Ruiz-Rebollo ML, Garcia-Rayado G, Lozada-Hernandez EE, Pereira J, Negoi I, Espina S, Hollenbach M, Litvin A, Bolado-Concejo F, Vargas RD, Pascual-Moreno I, Singh VK, Mira JJ. Design and validation of a patient-reported outcome measure scale in PMID 32245906
• Xu X, Ding L, Chen T, Liu G, Deng L, Sheng J, Zhu C, Sheng J, Zhang H, Wu D, He W, Xia L, Luo L, Xiong H, Lu NH, Ke L, Zhu Y; Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG). Efficacy and safety of intensive triglyceride-lowering therapy on reducing recurrence of hypertriglyceridemia-associated pancreatitis (REDUCE): protocol for a multicentre, randomised controlled trial. BMJ Open. 2025 PMID 40681200
• Wang Q, Wang G, Qiu Z, He X, Liu C. Elevated Serum Triglycerides in the Prognostic Assessment of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Observational Studies. J Clin Gastroenterol. 2017 Aug;51(7):586-593. doi: 10.1097/MCG.0000000000000846. PMID 28682990
• Scherer J, Singh VP, Pitchumoni CS, Yadav D. Issues in hypertriglyceridemic pancreatitis: an update. J Clin Gastroenterol. 2014 Mar;48(3):195-203. doi: 10.1097/01.mcg.0000436438.60145.5a. PMID 24172179
• Trikudanathan G, Yazici C, Evans Phillips A, Forsmark CE. Diagnosis and Management of Acute Pancreatitis. Gastroenterology. 2024 Sep;167(4):673-688. doi: 10.1053/j.gastro.2024.02.052. Epub 2024 May 15. PMID 38759844
• Tsai MS, Lin CL, Hsu YC, Lee HM, Kao CH. Long-term risk of pancreatitis and diabetes after cholecystectomy in patients with cholelithiasis but no pancreatitis history: a 13-year follow-up study. Eur J Intern Med. 2015 Sep;26(7):540-4. doi: 10.1016/j.ejim.2015.06.013. Epub 2015 Jul 2. PMID 26143191
• Nreu B, Dicembrini I, Tinti F, Mannucci E, Monami M. Cholelithiasis in patients treated with Glucagon-Like Peptide-1 Receptor: An updated meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2020 Mar;161:108087. doi: 10.1016/j.diabres.2020.108087. Epub 2020 Feb 19. PMID 32084455

Identifiers

NCT: NCT07617155 · 2026-RECAP-GLP1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗