Safety of Stopping Pancreatic Enzyme Replacement Therapy in Children With Improved Pancreatic Function After Highly Effective Modulator Therapy

NCT07632768 | Completed DMC

• 1 other identifier: 24152
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the safety of stopping pancreatic enzyme replacement therapy (PERT) in children with cystic fibrosis (CF) receiving CFTR modulator therapy (CFTRm) who have regained pancreatic sufficiency. The main questions it aims to answer are:

• Complete study visits and assessments over 6 months
• Continue or discontinue PERT based on study assignment
• Undergo anthropometric measurements
• Complete questionnaires about gastrointestinal symptoms
• Provide blood samples to assess vitamin levels and coagulation markers
• Provide stool samples to measure fecal elastase-1 (FE-1) and evaluate pancreatic function

Conditions

Pancreatic Insufficiency; Pancreas Disease; CFTR Gene Mutation; Cystic Fibrosis (CF); Exocrine Pancreatic Insufficiency; Exocrine Pancreatic Insufficiency in Subjects With Cystic Fibrosis

Keywords

cystic fibrosis; Pancreatic Insufficiency; Pancreatic Function Recovery; Exocrine Pancreatic Insufficiency; Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator Therapy; CFTR modulator; HEMT; Highly Effective Modulator Therapy

Outcome Measures

Primary Outcomes (3)

• Body Mass Index (BMI)

  Description: BMI calculated as body weight in kilograms divided by height in meters squared (kg/m²), using weight and height measurements obtained at each study visit. Time Frame: Baseline (Day 0 ± 28 days), Day 90 ± 28 days, Day 180 ± 28 days Type: Continuous

  6 months

• Weight (kg)

  Description: Participant body weight measured using a calibrated digital clinical scale. Weight will be recorded in kilograms (kg) to the nearest 0.1 kg. Time Frame: Baseline (Day 0 ± 28 days), Day 90 ± 28 days, Day 180 ± 28 days Type: Continuous

  6 months

• Height (cm)

  Description: Participant standing height measured using a wall-mounted stadiometer. Height will be recorded in centimeters (cm) to the nearest 0.1 cm. Time Frame: Baseline (Day 0 ± 28 days), Day 90 ± 28 days, Day 180 ± 28 days Type: Continuous

  6 months

Secondary Outcomes (13)

• Gastrointestinal Symptom Severity Total Score (PAGI-SYM Total Score)

  6 months

• Heartburn/Regurgitation Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Heartburn/Regurgitation Domain Score)

  6 months

• Nausea/Vomiting Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Nausea/Vomiting Domain Score)

  6 months

• Postprandial Fullness/Early Satiety Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Postprandial Fullness/Early Satiety Domain Score)

  6 months

• Bloating Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Bloating Domain Score)

  6 months

Study Arms (1)

Intervention: Discontinuation of Pancreatic Enzyme Replacement Therapy

EXPERIMENTAL

Participants with cystic fibrosis who demonstrate pancreatic sufficiency, defined as fecal elastase-1 (FE-1) ≥200 µg/g after treatment with CFTR modulator therapy, will discontinue pancreatic enzyme replacement therapy (PERT) under medical supervision. Participants will undergo follow-up assessments over 6 months, including monitoring of growth, gastrointestinal symptoms, nutritional laboratory markers, and repeat fecal elastase testing to evaluate the safety and sustainability of pancreatic function recovery after PERT discontinuation.

Drug: Discontinuation of Pancreatic Enzyme Replacement Therapy

Interventions

Discontinuation of Pancreatic Enzyme Replacement Therapy DRUG

Participants with cystic fibrosis who demonstrate pancreatic sufficiency, defined as fecal elastase-1 (FE-1) ≥200 µg/g after treatment with CFTR modulator therapy, will discontinue pancreatic enzyme replacement therapy (PERT) under medical supervision. Participants will undergo follow-up assessments over 6 months, including monitoring of growth, gastrointestinal symptoms, nutritional laboratory markers, and repeat fecal elastase testing to evaluate the safety and sustainability of pancreatic function recovery after PERT discontinuation.

Intervention: Discontinuation of Pancreatic Enzyme Replacement Therapy

Eligibility Criteria

• Age: 0 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of cystic fibrosis.
• History of pancreatic insufficiency, documented by a prior fecal elastase-1 (FE-1) concentration \<200 µg/g stool.
• Current pancreatic sufficiency at study entry, defined as fecal elastase-1 (FE-1) concentration ≥200 µg/g stool after treatment with a CFTR modulator.
• Age ≤18 years.
• Current use of a CFTR modulator, including ivacaftor, elexacaftor/tezacaftor/ivacaftor, or vanzacaftor/tezacaftor/deutivacaftor.

You may not qualify if:

• CF-related diabetes requiring current insulin use
• Advanced CF liver disease as defined by nodular liver, advanced fibrosis (F4), multi-lobular cirrhosis with or without portal hypertension, non-cirrhotic portal hypertension
• Short gut syndrome as defined by need for surgical bowel resection and subsequent need for parenteral nutrition for \> 60 days or bowel length less than 25%
• Moderate to severe malnutrition, defined as a BMI-for-age z score ≤ -2 for participants aged ≥2 years or a weight-for-length z score ≤ -2 for participants aged \<2 years

Sponsors & Collaborators

• Indiana University: lead
• Indiana Clinical and Translational Sciences Institute: collaborator

Study Sites (1)

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Related Publications (24)

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MeSH Terms

Conditions

Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Pancreatic Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Gastroenterology, Hepatology, and Nutrition Fellow

Study Record Dates

• First Submitted: May 26, 2026
• First Posted: June 8, 2026
• Study Start: December 3, 2024
• Primary Completion: August 8, 2025
• Study Completion: January 21, 2026
• Last Updated: June 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available beginning 6 months after publication of the primary study results and ending 5 years after publication.
• Access Criteria: Deidentified individual participant data (IPD) and supporting study documents may be made available to qualified researchers, academic investigators, or healthcare professionals whose proposed use of the data is consistent with the study objectives and approved by the study investigators and institution. Shared materials may include deidentified datasets underlying published results, the study protocol, statistical analysis plan, and informed consent form. Data will be shared upon reasonable request and may require execution of a data use agreement and compliance with institutional policies and applicable privacy and confidentiality regulations. Data will be provided electronically in a secure format.

Locations

US (1)