Endotherapy for Painless Chronic Pancreatitis (EACH)

Effect of Endotherapy on the Progression of Chronic Pancreatitis in Painless Patients

This is a prospective randomized controlled trial. . Patients will be divided into conservative or endoscopic group and fecal pancreatic elastase-1 (FE-1) is tested to evaluate pancreatic exocrine function. The effect of extracorporeal shock wave lithotripsy and endoscopic treatment on the progression of chronic pancreatitis in painless patients will be determined.

Study Overview

• Status: Recruiting
• Conditions: Abdominal Pain; Pancreatitis, Chronic; Exocrine Pancreatic Insufficiency; Cholangiopancreatography, Endoscopic Retrograde
• Intervention / Treatment: Procedure: extracorporeal shock wave lithotripsy and endoscopic drainage of the main pancreatic duct; Drug: pancreatic enzyme(Pancreatin Enteric-coated Capsules or Oryz-Aspergillus Enzyme and Pancreatin Table), antidiabetic medicine(Acarbose Tablets, Glucophage, Glimepirde Tablets)

Detailed Description

This is a prospective, randomized controlled trial. Patients will be divided into conservative or endoscopic group and FE-1 is tested to evaluate pancreatic exocrine function. The effect of extracorporeal shock wave lithotripsy and endoscopic treatment on the progression of chronic pancreatitis in painless patients will be determined.

Chronic pancreatitis (CP) is a pathologic fibro-inflammatory syndrome of the pancreas that eventually leads to damage of the gland in individuals with genetic, environmental and/or other risk factors. If widespread, this damage causes failure of exocrine and endocrine pancreatic function resulting in steatorrhea and diabetes. The global pooled incidence of CP is 10 cases [95% Confidence interval (CI) 8-12] per 100,000 general population per year. Endoscopic retrograde cholangiopancreatography (ERCP) and extracorporeal shock wave lithotripsy (ESWL) has become first-line therapy for patients with chronic pancreatitis according to guidelines. Endoscopic therapy has been proved effective and safe. The clearance rate of pancreatic stones was 42-76%, and the pain relief rate was 15-85%.

Pain is the major clinical features of CP and remained a major clinical challenge. It is present in up to 90% of patients and is the main cause of hospitalization in most patients.Patten of pain for patients with chronic pancreatitis differs widely.

However, some CP patients have never had abdominal pain during the course of the disease, and participants are often diagnosed with CP due to diabetes or steatorrhea, which are called painless CP, accounting for about 10% of the CP population. These patients are mainly characterized as pancreatic endocrine and exocrine insufficiency. Some studies proposed that painless CP may be related to the severity of inflammation and the pain sensitivity of patients, but the mechanism has not yet been elucidated.

It is still controversial whether painless CP requires active endoscopic intervention or not. The United European Gastroenterology evidence-based guidelines does not recommend endoscopic treatment in painless CP patients, but the recommendation is not supported by strong clinical research evidence. European Society of Gastrointestinal Endoscopy (ESGE) Guideline proposed whether active endoscopic treatment had a protective effect on the pancreatic function of patients with painless CP is still unconfirmed. On the contrary, a small sample study consisting of 41 CP patients by Katsushi found that endoscopic treatment can delay the progression of exocrine dysfunction in CP patients.Considering these contradicting results, it is urgent to conduct a clinical study to determine the effect of endoscopic treatment on preservation of pancreatic function in patients with CP.

Therefore, this study intends to use clinical prospective trials to explore whether patients with painless CP can benefit from active endoscopic minimally invasive interventions (including ERCP, ESWL, etc.), including slowing down the deterioration of pancreatic endocrine and exocrine function and improving patients' life quality and other aspects, and then provide an important reference basis for the clinical treatment of this type of patients.

Considering all these backgrounds, the primary outcome aimed to explore whether painless CP patients can benefit from endoscopic interventions (including ERCP, ESWL, etc.), including slowing down the deterioration of pancreatic endocrine and exocrine function, improving patients' life quality and other aspects. Based on the above, this study intends to provide important reference for the clinical treatment of painless CP patients.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhuan Liao; Phone Number: 13061921980; Email: liaozhuan@smmu.edu.cn
• Study Contact Backup: Name: Yangyang Qian; Phone Number: 13818040017; Email: drfionachien@163.com

Study Locations

• China
  • Shanghai, China, 200433
    • Recruiting
    • Changhai Hospital
    • Sub-Investigator: Lianghao Hu
    • Sub-Investigator: Yangyang Qian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosed with chronic pancreatitis without pain attack related with chronic pancreatitis;
• calcified stone in the cephalic or corporeal portion of the main pancreatic duct with upstream duct dilation;
• no ERCP or ESWL carried out before admission;

Exclusion Criteria:

• suspected to have malignant tumors;
• history of pancreatic surgery or gastrojejunostomy (Billroth II);
• with end-stage disease;
• pregnancy or lactation;
• refuse to write informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endoscopic group; The patients received intravenous analgesia (flurbiprofen and remifentanil) before the ESWL (Compact Delta II; Dornier Med Tech, Wessling, Germany). After the last ESWL session, the patients are treated with following ERCP within 48h. ERCP was performed under conscious sedation with intramuscular administration of diazepam 2.5-5.0 mg and pethidine 25-50 mg. If necessary, endoscopic sphincterotomy was performed. A dilating bougie or balloon will be used to dilate the stenosis after sphincterotomy. Standard techniques (i.e., extraction basket, extraction balloon, or both) will be used for stone removal. A pancreatic duct stent for drainage and nasopancreatic catheters will be inserted for temporary drainage if necessary. Conservative treatments similar to patients in the control group were given in endoscopic group according to patients' condition.	Procedure: extracorporeal shock wave lithotripsy and endoscopic drainage of the main pancreatic duct; In addition to drug administrated in the control group, patients in this group would be treated with ESWL and endoscopic drainage of the main pancreatic duct.; Other Names: ESWL; ERCP
Other: Conservative group; Patients will have pancreatic enzymes (Pancreatin Enteric-coated Capsules or Oryz-Aspergillus Enzyme and Pancreatin Table) to control symptoms of exocrine pancreatic insufficiency. The recommended initial dose for adults is (25 000-40 000) IU lipase per meal (40 000 IU for meals and 20 000 IU for snacks), which can be increased until the PEI is relieved. The maximum recommended dose is (75 000-80 000) IU lipase per meal. Actions including drugs(Acarbose Tablets, Glucophage, Glimepirde Tablets) or insulin(Biosynthetic Human Insulin Injection, Tresiba or both) would also be taken for control of diabetes according to patients' glucose levels.	Drug: pancreatic enzyme(Pancreatin Enteric-coated Capsules or Oryz-Aspergillus Enzyme and Pancreatin Table), antidiabetic medicine(Acarbose Tablets, Glucophage, Glimepirde Tablets); Patients will receive drugs to control pancreatic insufficiency

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
exocrine function of the pancreas assessed by the value of fecal elastase in μg/g	Pancreatic exocrine function insufficiency(PEI) is defined as fecal elastase <200 μg/g. The result wii be divided into 4 conditions, including normal exocrine function, newly developed PEI, PEI relief, PEI persisting.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
endocrine function of the pancreas assessed by glycosylated hemoglobin in %.	It is considered as pancreatic endocrine function insufficiency when glycosylated hemoglobin >6.5%， the result of pancreatic endocrine function can also be divided into 4 parts similar to that of pancreatic exocrine function.	12 months
endocrine function of the pancreas assessed by fasting blood glucose in mmol/L	It is considered as pancreatic endocrine function insufficiency when fasting blood glucose >6.1mmol/L, the result of pancreatic endocrine function can also be divided into 4 parts similar to that of pancreatic exocrine function.	12 months
endocrine function of the pancreas assessed by fasting C peptide in ug/L	It is considered as pancreatic endocrine function insufficiency when fasting C peptide<1.1ug/L, the result of pancreatic endocrine function can also be divided into 4 parts similar to that of pancreatic exocrine function.	12 months
life quality assessed by SF-36 questionnaire	life quality assessed by the MOS item short from health survey (SF-36) questionnaire	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMI in kg/m^2	Body Mass Index (BMI) is a person's weight in kilograms divided by the square of height in meters.	12 months
Treatment-related costs in RMB from initial enrollment to the end of the study	The total costs in RMB of each hospitalization	12 months

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Investigators: Principal Investigator: Zhuan Liao, MD, Shanghai Changhai Hospital, Shanghai, China

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: November 24, 2021
• First Submitted That Met QC Criteria: February 26, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 26, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: endoscopic retrograde cholangiopancreatography; chronic pancreatitis; Exocrine Pancreatic Insufficiency; painless
• Additional Relevant MeSH Terms: Digestive System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Pancreatic Diseases; Abdominal Pain; Pancreatitis; Pancreatitis, Chronic; Exocrine Pancreatic Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Metformin; Acarbose; Pancrelipase; Pancreatin
• Other Study ID Numbers: Painless CP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No