Endotherapy and/or Extracorporeal Shockwave Lithotripsy for Painless Chronic Pancreatitis

Not Applicable

Recruiting

• Conditions: Painless Chronic Pancreatitis
• Interventions: Behavioral: Lifestyle modifications; Drug: Pancreatic enzyme (Pancreatin Enteric-coated Capsules or Oryz-Aspergillus Enzyme and Pancreatin Table), antidiabetic medicine(Acarbose , Metformin, Glimepirde Tablets, Insulin); Procedure: Endoscopic Retrograde Cholangiopancreatography (ERCP) and/or Extracorporeal Shockwave Lithotripsy (ESWL)

• Registration Number: NCT07074379
• Lead Sponsor: Changhai Hospital

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-06-29
• Study First Submitted QC: 2025-07-10
• Study First Posted: 2025-07-20
• Study Start: 2025-07-21
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-01
• Last Update Posted: 2025-08-06
• Primary Completion: 2027-08-01
• Study Completion: 2027-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 126

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Endotherapy and/or Extracorporeal Shockwave Lithotripsy Group	Lifestyle modifications	Participants in this arm will undergo a comprehensive treatment approach that includes lifestyle modifications, pharmacological interventions, and procedural therapies such as endoscopic retrograde cholangiopancreatography (ERCP) and/or extracorporeal shockwave lithotripsy (ESWL).
Conservative Treatment Group	Pancreatic enzyme (Pancreatin Enteric-coated Capsules or Oryz-Aspergillus Enzyme and Pancreatin Table), antidiabetic medicine(Acarbose , Metformin, Glimepirde Tablets, Insulin)	This arm includes participants who will receive standard conservative management for painless chronic pancreatitis. The treatment regimen comprises lifestyle modification and medications to manage symptoms of pancreatic exocrine and endocrine insufficiency, such as pancreatic enzyme supplements and medications for diabetes management (e.g., oral hypoglycemics or insulin).
Endotherapy and/or Extracorporeal Shockwave Lithotripsy Group	Pancreatic enzyme (Pancreatin Enteric-coated Capsules or Oryz-Aspergillus Enzyme and Pancreatin Table), antidiabetic medicine(Acarbose , Metformin, Glimepirde Tablets, Insulin)	Participants in this arm will undergo a comprehensive treatment approach that includes lifestyle modifications, pharmacological interventions, and procedural therapies such as endoscopic retrograde cholangiopancreatography (ERCP) and/or extracorporeal shockwave lithotripsy (ESWL).
Endotherapy and/or Extracorporeal Shockwave Lithotripsy Group	Endoscopic Retrograde Cholangiopancreatography (ERCP) and/or Extracorporeal Shockwave Lithotripsy (ESWL)	Participants in this arm will undergo a comprehensive treatment approach that includes lifestyle modifications, pharmacological interventions, and procedural therapies such as endoscopic retrograde cholangiopancreatography (ERCP) and/or extracorporeal shockwave lithotripsy (ESWL).
Conservative Treatment Group	Lifestyle modifications	This arm includes participants who will receive standard conservative management for painless chronic pancreatitis. The treatment regimen comprises lifestyle modification and medications to manage symptoms of pancreatic exocrine and endocrine insufficiency, such as pancreatic enzyme supplements and medications for diabetes management (e.g., oral hypoglycemics or insulin).

Primary Outcome Measures

Name	Time	Method
Acute Pancreatitis Incidence	12 months	The incidence of acute pancreatitis assessed by Revised Atlanta Classification over a 12-month period following randomization.

Secondary Outcome Measures

Name	Time	Method
Incidence and Severity of Pancreatic Pain	12 months	The incidence and severity of pancreatic pain over a 12-month period. Pain severity will be measured using the Visual Analogue Scale (VAS), where patients rate their pain on a scale from 0 (no pain) to 10 (worst possible pain).
Glycosylated Hemoglobin Level	12 months	This outcome measure evaluates the percentage of hemoglobin that is glycosylated, reflecting the average blood glucose levels over the past 2 to 3 months. It is a key indicator of long-term glycose level in patients.
Fasting Blood Glucose Level	12 months	This outcome measure assesses the level of glucose in the blood after an overnight fast. Fasting glucose is a standard test for diagnosing diabetes and monitoring diabetes control. It provides a snapshot of the body's ability to manage glucose without the influence of food.
Glucose Area Under the Curve (AUC) Post MMTT	12 months	This outcome assesses the total glucose exposure over the first 2 hours following a Mixed Meal Tolerance Test (MMTT). The AUC is determined using Riemann sums based on the midpoint of each interval (0, 30, 60, 90, and 120 minutes). This metric is essential for evaluating the body's glucose handling ability and the effectiveness of glucose control.
Insulin Area Under the Curve (AUC) Post MMTT	12 months	This outcome measures the total insulin exposure over the first 2 hours following a Mixed Meal Tolerance Test (MMTT). The AUC is calculated using Riemann sums based on the midpoint of each interval (0, 30, 60, 90, and 120 minutes). This metric is vital for assessing the overall insulin secretion response to a meal and the effectiveness of insulin production.
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	12 months	The HOMA-IR is calculated from fasting glucose and fasting insulin levels obtained during the MMTT. It provides an estimate of insulin resistance and is calculated using the formula: HOMA-IR= (fasting glucose × fasting insulin)/405. This index is crucial for understanding the body's insulin sensitivity.
Severity of Acute Pancreatitis	12 months	The severity of acute pancreatitis episodes that occur within 12 months post randomization. Severity will be graded according to the Atlanta Classification criteria, which categorizes pancreatitis into mild, moderate, and severe based on clinical and imaging findings.
Pancreatic Exocrine Function	12 months	This outcome assesses changes in pancreatic exocrine function by measuring fecal elastase-1 levels at baseline and 12 months post randomization.
Fasting C-Peptide Concentration	12 months	This outcome measure determines the concentration of C-peptide in the blood during a fasting state. C-peptide is a byproduct of insulin production and provides an index of endogenous insulin secretion. It is useful for assessing insulin production capacity.
C-peptide Area Under the Curve (AUC) Post MMTT	12 months	This outcome measures the total exposure to C-peptide over the first 2 hours following a mixed meal tolerance test (MMTT). The AUC is calculated using Riemann sums based on the midpoint of each interval (0, 30, 60, 90, and 120 minutes). This metric is crucial for assessing the overall insulin secretion capacity of the islets.
Disposition Index for C-peptide	12 months	The disposition index for C-peptide is calculated as (ΔC-peptide30-0min / Δglucose30-0min) × (1 / fasting C-peptide). It represents the ratio of insulin or C-peptide secretion to sensitivity and is an important indicator of the overall β-cell function and insulin sensitivity.
Quality of Life Assessed by SF-36	12 months	This outcome evaluates the quality of life (QoL) of patients with painless chronic pancreatitis at two time points: at baseline (time of hospital admission) and at 12 months post-randomization. The assessment is conducted using the Short Form Health Survey (SF-36), a widely recognized and validated tool that measures health-related quality of life across eight dimensions: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The SF-36 provides a comprehensive overview of how the condition and treatment affect the patients' overall well-being and daily functioning.
Homeostatic Model Assessment of β-cell Function (HOMA-b)	12 months	HOMA-b is determined by the formula HOMA b = (fasting insulin × 360)/(fasting glucose - 63) to assess insulin secretion. It provides an estimate of the β-cell function in response to fasting glucose levels.
Insulinogenic Index Post MMTT	12 months	The insulinogenic index is a measure of the early insulin response to a glucose challenge, calculated as (Δinsulin30-0min / Δglucose30-0min). It reflects the capacity of the β-cells to secrete insulin in response to a rise in blood glucose levels.
C-peptide Secretion Index Post MMTT	12 months	This index is calculated by replacing insulin with C-peptide in the insulinogenic index formula, i.e., (ΔC-peptide30-0min / Δglucose30-0min). It serves as a measure of the early C-peptide response to a glucose challenge, providing information about the secretory capacity of the islets.

Trial Locations

Locations (1)

Changhai Hospital; 🇨🇳 Shanghai, Shanghai, China