Endotherapy and/or Extracorporeal Shockwave Lithotripsy for Painless Chronic Pancreatitis

Official title

Endotherapy and/or Extracorporeal Shockwave Lithotripsy Versus Conservative Treatment in Painless Chronic Pancreatitis

Overview

Chronic pancreatitis (CP) is caused by factors such as genetics and the environment, leading to the destruction of pancreatic tissue, infiltration of inflammatory cells, and progressive fibrosis of the pancreas. As the disease progresses, pancreatic tissue is damaged, resulting in impaired endocrine and exocrine functions, manifesting as symptoms like steatorrhea and diabetes. Pain associated with chronic pancreatitis (PACP) is the most common symptom in CP patients. Approximately 75% of patients initially present with abdominal pain, and previous studies have shown that PACP can occur in 85-97% of CP patients. However, there is a type of pancreatitis where patients do not experience abdominal pain and typically seek medical attention due to routine check-ups or symptoms of pancreatic endocrine and exocrine dysfunction; this particular type of pancreatitis is known as painless CP. A meta-analysis showed that painless CP accounts for about 12% of all CP patients. In patients with CP, continuous pancreatic damage leads to the destruction of pancreatic tissue, subsequently causing insufficiency in both exocrine and endocrine functions. "Painless" does not equate to "harmless"; patients with painless CP often present with severe symptoms of pancreatic exocrine and endocrine dysfunction at the time of diagnosis. These findings underscore the importance of early identification and active management of patients with painless CP. Whether active endoscopic intervention is needed for painless CP remains a matter of debate. The European Society of Gastrointestinal Endoscopy (ESGE) suggests endoscopic therapy and/or extracorporeal shockwave lithotripsy (ESWL) as the first-line therapy for painful uncomplicated chronic pancreatitis (CP) with an obstructed main pancreatic duct (MPD) in the head/ body of the pancreas; however, due to the unclear potential benefits (preservation of pancreatic function) of endoscopic and/or ESWL treatment for painless CP, it is not recommended for patients without pain, although the evidence is of low quality. Although there is currently no consensus on whether endoscopic treatment can protect the pancreatic function of patients with painless chronic pancreatitis, preliminary evidence suggests that endoscopic treatment may have a positive impact on pancreatic atrophy and dysfunction in patients with painless CP. In a retrospective study by Ikeura et al., which included 268 patients with CP and painless pancreatic duct stones, it was found that endoscopic treatment and complete clearance of stones in patients with painless pancreatic duct stones helped maintain the volume of the pancreatic parenchyma. Although preliminary research suggests that endoscopic treatment may protect pancreatic function in patients with painless CP, it could also trigger pain. A study by Ikeura et al. found that painless CP patients who underwent endoscopic treatment but did not have complete clearance of pancreatic duct stones were at a significantly higher risk of developing pain. This indicates that incomplete endoscopic treatment might lead patients from a painless state to one of pain. However, a study by Amodio et al. suggests that the likelihood of painless CP patients experiencing pain in the short term is low, implying that conservative treatment might be more appropriate. Current research on the clinical characteristics of painless CP and its response to treatment is relatively limited, necessitating further clinical studies to clarify the impact of ERCP and/or ESWL on these patients. We plan to conduct a randomized controlled trial to assess whether these minimally invasive interventions can improve clinical outcomes for patients with painless CP

Interventions

• Behavioral Lifestyle modifications
  Lifestyle modifications primarily include quitting smoking and alcohol consumption, as well as engaging in physical exercise.
• Drug Pancreatic enzyme (Pancreatin Enteric-coated Capsules or Oryz-Aspergillus Enzyme and Pancreatin Table), antidiabetic medicine(Acarbose , Metformin, Glimepirde Tablets, Insulin)
  This intervention involves the use of medications to control the pancreatic exocrine and endocrine dysfunction caused by chronic pancreatitis. 1. Pancreatic enzyme therapy: Patients will use pancreatic enzymes (pancreatin enteric-coated capsules or oryz-aspergillus enzyme and pancreatin tablets) to control the symptoms of exocrine pancreatic insufficiency. 2. Diabetes treatment: Patients with diabetes will also use antidiabetic medications (such as oral hypoglycemic drugs or insulin, depending
• Procedure Endoscopic Retrograde Cholangiopancreatography (ERCP) and/or Extracorporeal Shockwave Lithotripsy (ESWL)
  This intervention involves the application of endoscopic retrograde cholangiopancreatography (ERCP) and/or extracorporeal shockwave lithotripsy (ESWL), conducted in accordance with established clinical guidelines. The procedures are tailored to the individual patient's condition, which may include sphincterotomy, balloon dilation of pancreatic duct strictures, stone extraction, and stent placement as indicated. ESWL may be used prior to ERCP to fragment pancreatic duct stones, facilitating their

Primary outcome measures

• Acute Pancreatitis Incidence [Time frame: 12 months]

Secondary outcome measures (12)

• Severity of Acute Pancreatitis [Time frame: 12 months]
• Incidence and Severity of Pancreatic Pain [Time frame: 12 months]
• Pancreatic Exocrine Function [Time frame: 12 months]
• Glycosylated Hemoglobin Level [Time frame: 12 months]
• Fasting Blood Glucose Level [Time frame: 12 months]
• Fasting C-Peptide Concentration [Time frame: 12 months]
• C-peptide Area Under the Curve (AUC) Post MMTT [Time frame: 12 months]
• Glucose Area Under the Curve (AUC) Post MMTT [Time frame: 12 months]
• Insulin Area Under the Curve (AUC) Post MMTT [Time frame: 12 months]
• Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [Time frame: 12 months]
• Homeostatic Model Assessment of β-cell Function (HOMA-b) [Time frame: 12 months]
• Insulinogenic Index Post MMTT [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Adults aged 18-85 years.
• Diagnosed with painless chronic pancreatitis.
• No prior history of endoscopic retrograde cholangiopancreatography (ERCP) or extracorporeal shockwave lithotripsy (ESWL) treatment.

Exclusion criteria

• Presence of complications requiring endoscopic or surgical intervention, such as pancreatic pseudocysts, benign biliary strictures, or pancreatic fistulas.
• Autoimmune pancreatitis.
• Suspected malignancy.
• History of pancreatic surgery or gastrointestinal bypass surgery (e.g., Billroth II procedure).
• End-stage disease.
• Pregnancy or lactation.
• Contraindications to ESWL or ERCP.
• Refusal to provide informed consent.

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

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Changhai Hospital — Shanghai

Identifiers

NCT: NCT07074379 · PCP

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗