Hypertriglyceridemia, Hypertriglyceridemia Induced Acute Pancreatitis, Pancreatitis Relapsing, Recurrent Acute Pancreatitis
Conditions
Keywords
hypertriglyceridemia-induced acute pancreatitis, recurrent acute pancreatitis, semaglutide, GLP-1 receptor agonist, pancreatitis prevention
Brief summary
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
DRUGSemaglutide
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.
DRUGPlacebo (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.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with recurrent hypertriglyceridemia-induced acute pancreatitis | Within 18 months after randomization | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of recurrent hypertriglyceridemia-induced acute pancreatitis episodes | 18 months after randomization | Total number of recurrent HTG-AP episodes experienced by each participant during follow-up. |
| Change in fasting serum triglyceride level | Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months | Change in fasting serum triglyceride concentration from baseline. |
| Change in PAN-PROMISE score | Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months | Change in patient-reported outcomes measured using the PAN-PROMISE questionnaire. PAtieNt-rePoRted OutcoMe scale in acute pancreatItis, an international proSpEctive cohort study, (PAN-PROMISE scale) was designed and validated to evaluate the symptoms that cause the greatest discomfort and concern to patients with AP. They include pain, abdominal distension, difficulty eating, difficulty with bowel movements, nausea or vomiting, thirst, and weakness. Each symptom is scored (highest intensity in the last 24 hours) by the patient from 0 (none) to 10 (maximum possible intensity according to the patient's judgment), with a total score ranging from 0 to 70. |
| Change in lipid profile parameters | Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months | Changes in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) from baseline. |
| Change in glycemic parameters | Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months | Changes in fasting serum glucose and hemoglobin A1C from baseline. |
| Change in anthropometric measures | Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months | Changes in body weight, body mass index (BMI), and waist circumference from baseline. |
| Change in smoking | Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months | Changes in self-reported smoking amount |
| Change in alcohol consumption | Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months | Changes in self-reported alcohol intake from baseline. |
| MRI assessment of hepatic and pancreatic fat infiltration and pancreatic volume | Baseline, 1 month, 3 months, 6 months, 12 months, and 18 months | Changes in MRI-based measurements of hepatic fat infiltration, pancreatic fat infiltration, and pancreatic volume from baseline. |
| Incidence of metabolic and pancreatic complications | Within 18 months after randomization | Incidence of stress hyperglycemia, post-acute pancreatitis diabetes mellitus, abdominal obesity, or pancreatic exocrine insufficiency. |
| Incidence of chronic pancreatitis | 18 months after randomization | Incidence of newly diagnosed chronic pancreatitis during follow-up. |
| Change in health-related quality of life | Baseline and 18 months after randomization | Change in EQ-VAS score from baseline. EQ VAS is a 0-100 scale where respondents are asked to indicate their overall health on the day they complete the questionnaire. It is a visual analog scale. The score ranges from 0 to 100 where 100 means the best health the patient can imagine, and 0 means the worst health the patient can imagine. |
| Pancreatitis-related unplanned readmission rate | 18 months after randomization | Rate of unplanned hospital readmissions related to pancreatitis. |
| All-cause mortality | 18 months after randomization | Death from any cause during study follow-up. |
Countries
China
Contacts
CONTACTDong Wu, Medical Doctor
Outcome results
None listed