Pancreatic Enzyme Replacement Therapy for Acute Pancreatitis-Associated Exocrine Pancreatic Insufficiency (PERT-AP)

Pancreatic Enzyme Replacement Therapy for Acute Pancreatitis-Associated Exocrine Pancreatic Insufficiency: the PERT-AP Trial

This study aims to evaluate if a 6-month course of pancrelipase (CREON) treatment improves symptoms of exocrine pancreatic insufficiency (EPI) after an attack of acute pancreatitis. Diagnosis of EPI is measured by a fecal elastase value of <200, and patients must have a qualifying symptom burden based on the EPI symptom tracker survey. Blood and stool will be analyzed as part of this study, and other surveys of health status will be used to track improvement of symptoms.

Study Overview

• Status: Recruiting
• Conditions: Exocrine Pancreatic Insufficiency
• Intervention / Treatment: Drug: Pancrelipase Capsules

Detailed Description

This is a prospective, multi-center, open-label, single-arm study of pancrelipase (CREON) in eligible outpatient adults following an episode of acute pancreatitis. Following study eligibility evaluation and informed consent, patients will complete a 7-day run-in period without any pancreatic enzyme replacement therapy and complete baseline questionnaires and assessments, followed by a 180-day treatment period with pancrelipase. The study will end after a final 30 day-post pancrelipase treatment observation period during which safety events will be collected, and EPI symptom burden as well as stool frequency and consistency will be assessed as primary outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Zoe Krebs; Phone Number: 614-685-3619; Email: zoe.krebs@osumc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California
      • Principal Investigator: James Buxbaum, MD
      • Contact: Jorge Zuniga Gomez; Email: jorge.zunigagomez@med.usc.edu
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois Chicago
      • Contact: Haya Alrashdan, MSN; Phone Number: 312-413-0306; Email: halras2@uic.edu
      • Principal Investigator: Cemal Yazici, MD
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Not yet recruiting
      • University of Minnesota
      • Principal Investigator: Guru Trikudanathan, MD
      • Contact: Cathy Kneeland, RN; Email: kreel001@umn.edu
  • New York
    • New York, New York, United States, 10016
      • Withdrawn
      • New York University Langone Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University
      • Contact: Zoe Krebs, BA; Phone Number: 614-685-3619; Email: zoe.krebs@osumc.edu
      • Sub-Investigator: Peter Lee, MbCHb
      • Principal Investigator: Georgios Papachristou, MD, PhD
      • Contact: Samantha Terhorst, MS; Email: samantha.terhorst@osumc.edu
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh
      • Principal Investigator: Anna Phillips, MD
      • Contact: Apsara Mishra; Phone Number: 412-624-9310; Email: apm179@pitt.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult patients of age 18 or older, able to provide informed consent and follow all study procedures.
2. Stable outpatient up to 12 months following an acute pancreatitis episode and has EPI based on an FE-1 < 200 µg/g stool obtained within 3 months prior to baseline assessment (Visit 2).
3. Score of equal or greater 0.6 on the EPI symptom tracker at baseline Visit 2.
4. Must be off PERT (including prescription and non-prescription enzymes) for 7 days prior to baseline Visit 2.
5. Must have fully completed the terminal intervention for necrotizing pancreatitis (surgical or endoscopic necrosectomy or percutaneous drainage).
6. Have a Body Weight between 40 and 120 kg (amounts to 600-1800 LU/meal pancrelipase starting dose of pancrelipase).
7. Women of childbearing potential must have a negative urine pregnancy test at Study Day 1 and practicing at least one protocol specified method of birth control (Section 5.2.4), starting at Study Day 1 through 30 days after last dose of pancrelipase.

8. Females of non-childbearing potential (either postmenopausal or permanently surgically sterile as defined:

   • Age > 55 years with no menses for 12 or more months without an alternative medical cause.
   • Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause AND an FSH level > 40 IU/L.

OR

• Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

do not require pregnancy testing.

Exclusion Criteria:

1. Acute pancreatitis episode due to a pancreatic cystic neoplasm, trauma, or surgery. Post-ERCP acute pancreatitis patients can be enrolled.
2. History of definite chronic pancreatitis defined by APA Chronic Pancreatitis Guideline.1
3. Pancreas malignancy or other active malignancies requiring systemic treatment; treated basal cell carcinoma, and treated in-situ cervical cancer can be included.
4. Enteropathies, and gastroenteritis that may affect FE-1 levels, e.g., Inflammatory bowel disease, Celiac Disease, viral-, bacterial-, fungal-, or parasitic gastroenteritis.
5. Gastroparesis.
6. Confirmed or suspected cystic tumor associated with main pancreatic duct dilation or believed to be the cause of AP (in the site-PI's judgment).
7. Prior pancreatic surgery or GI tract surgery affecting the upper GI tract including but not limited to gastric bypass surgery, total pancreatectomy.
8. Pregnancy or breast feeding.
9. Patients with life expectancy of less than 6 months due to advanced chronic conditions, such as congestive heart failure or chronic obstructive pulmonary disease, or other conditions which preclude study participation by judgement of the investigator.
10. Incarcerated individuals

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pancrelipase; Pancrelipase (CREON) capsules taken orally with food, at a dose 36,000 units with snacks and 72,000 units with meals, for a total of 6 months (180 days)	Drug: Pancrelipase Capsules; Treatment with Pancreatic Enzyme Replacement Therapy; Other Names: CREON

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-Reported EPI Symptoms - Short Term	Determine the patient-reported change in total Exocrine Pancreatic Insufficiency (EPI) symptom score as measured by the EPI Symptom Tracker from baseline to 30 days of pancrelipase treatment; scored from 0 - 3, 0 being no symptoms and 3 being worst possible symptoms.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Stool Frequency	Record changes in stool frequency from baseline to 30 days and from baseline to the end of pancrelipase treatment (180 days)	180 days
Change in Stool Consistency	Record change in stool consistency from baseline to 30 days and from baseline to the end of pancrelipase treatment	180 days
Patient-Reported EPI Symptoms - LongTerm	Determine the patient-reported change in total Exocrine Pancreatic Insufficiency (EPI)symptom score as measured by the EPI Symptom Tracker from baseline to the end of pancrelipase treatment (180 days); scored from 0 - 3, 0 being no symptoms and 3 being worst possible symptoms.	180 days
Change in Depression Score	Change in depression score assessed by the Patient Health Questionnaire (PHQ-9) from baseline to 30 days and from baseline to end of pancrelipase treatment; scores range from 0 - 27, with a higher score meaning worse depression symptoms	180 days
Change in SF-12 Health Score	Change in self-assessment of health status as assessed by the 12-Item Short Form Survey (SF-12) from baseline to 30 days and from baseline to end of pancrelipase treatment (180 days); form is not numerically scored	180 days
Change in Global Health Score	Change in Global Health score assessed by the Global Health (PROMIS) Questionnaire. Each question is scored 1 - 5, with high values indicating better health status in the first part of the form, and high values indicating poor health status in the latter part of the form; also included is a 0-10 average pain scale.	180 days
Change in Nutrition Biomarkers - Vitamin D	Change in serum nutrition biomarker Vitamin D (ng/mL)	180 days
Change in Nutrition Biomarkers - Retinol Binding Protein	Change in serum nutrition biomarker Retinol Binding Protein (mg/dL)	180 days
Change in Nutrition Biomarkers - Pre-albumin	Change in serum nutrition biomarker Pre-albumin (mg/dL)	180 days
Change in Nutrition Biomarkers - Albumin	Change in serum nutrition biomarker Albumin (g/dL)	180 days
Medication Adherence	Medication adherence to be assessed by pill count and questions about dosing compliance in previous two weeks.	180 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency, Type, and Severity of Adverse Events	Evaluate the frequency, severity, and causality of adverse events (AEs), treatment emergent AEs (TEAEs), and serious AEs (SAEs); Descriptive assessment of safety and tolerability using FAS set with AEs collected from time of consent to 30 days after end of pancrelipase treatment	210 days
Change in Stool Frequency	Change in stool frequency from end of pancrelipase treatment to end of 30-day follow-up period	210 days
Change in Stool Consistency	Change in stool consistency from end of pancrelipase treatment to end of 30-day follow-up period	210 days
Patient-Reported EPI Symptoms - Post-Treatment	Change in total Exocrine Pancreatic Insufficiency (EPI) symptom score as measured by the EPI Symptom Tracker from end of pancrelipase treatment to end of 30-day follow-up period; scored from 0 - 3, 0 being no symptoms and 3 being worst possible symptoms.	210 days

Collaborators and Investigators

• Sponsor: Ohio State University
• Collaborators: AbbVie; New York University; University of Pittsburgh; University of Illinois at Chicago; University of Southern California; University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 13, 2024
• First Submitted That Met QC Criteria: June 21, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Exocrine Pancreatic Insufficiency; Hydrolases; Enzymes; Enzymes and Coenzymes; Complex Mixtures; Lipase; Carboxylic Ester Hydrolases; Esterases; Pancreatic Extracts; Tissue Extracts; Pancrelipase
• Other Study ID Numbers: 2023H0394

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes