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Completed

NCT Number: NCT07632768

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

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:

1. Does discontinuation of PERT affect gastrointestinal symptoms, nutritional status, pancreatic function, or body composition over 6 months? 2. Does stopping PERT increase gastrointestinal symptoms or affect nutritional status, pancreatic function, or body composition compared with continuing PERT?

Researchers will evaluate changes in growth, gastrointestinal symptoms, vitamin levels, pancreatic function, and body composition following PERT discontinuation.

Participants will:

* 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

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Key information

Conditions

Cystic Fibrosis (CF) CFTR Gene Mutation Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cystic Fibrosis Digestive System Diseases Exocrine Pancreatic Insufficiency Exocrine Pancreatic Insufficiency in Subjects With Cystic Fibrosis Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Pancreas Disease Pancreatic Diseases Pancreatic Insufficiency Respiratory Tract Diseases

Age range

0 year–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

About this study

This prospective clinical trial will evaluate the safety and feasibility of discontinuing pancreatic enzyme replacement therapy (PERT) in children with cystic fibrosis (CF) who regain pancreatic sufficiency after treatment with cystic fibrosis transmembrane conductance regulator modulators (CFTRm).

Pancreatic insufficiency is a common complication of CF and is typically treated with lifelong PERT. Recent studies and case reports have shown that some individuals receiving CFTR modulators experience improvement or normalization of pancreatic function, as measured by fecal elastase-1 (FE-1) levels. However, there is limited evidence regarding the safety of stopping PERT after pancreatic function recovery. This study aims to address this knowledge gap by prospectively evaluating growth, gastrointestinal symptoms, nutritional status, and pancreatic function after PERT withdrawal.

Eligible participants are children and adolescents aged 18 years or younger with cystic fibrosis and a history of pancreatic insufficiency who are receiving CFTR modulator therapy. Participants will undergo fecal elastase testing at enrollment and will be assigned to study groups based on pancreatic function status. Participants with FE-1 levels ≥200 µg/g will discontinue PERT under medical supervision, while participants with FE-1 levels <200 µg/g will continue standard therapy.

Study assessments will include growth measurements, gastrointestinal symptom questionnaires, laboratory monitoring of fat-soluble vitamins and liver function, CFTR modulator trough levels, and repeat fecal elastase testing. Body composition will also be evaluated. Participants who discontinue PERT will undergo close clinical monitoring throughout the study period for signs of malabsorption, poor weight gain, recurrent pancreatic insufficiency, or pancreatitis. PERT may be restarted if clinically indicated.

The study will also explore factors associated with successful recovery of pancreatic function and sustained pancreatic sufficiency, including demographic characteristics, nutritional status, medication history, and laboratory markers. In addition, optional biospecimen storage will allow future analyses of the metabolome and microbiome related to pancreatic function and CFTR modulator response.

This study is intended to provide feasibility and safety data to support future larger multicenter trials and to improve individualized treatment strategies for children with CF who experience recovery of pancreatic function after CFTR modulator therapy.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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

Treatment and study plan

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.

Primary outcomes

  1. Body Mass Index (BMI)

    Time frame: 6 months

    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

  2. Weight (kg)

    Time frame: 6 months

    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

  3. Height (cm)

    Time frame: 6 months

    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

Secondary outcomes

  1. Gastrointestinal Symptom Severity Total Score (PAGI-SYM Total Score)

    Time frame: 6 months

    Description: Participants complete the validated Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). The PAGI-SYM total score is calculated as the mean of all completed items and ranges from 0 (none) to 5 (very severe). Higher scores indicate worse gastrointestinal symptom severity.

    Time Frame: Day 0 ± 28 days (pre-intervention), Day 90 ± 28 days, Day 180 ± 28 days.

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

    Time frame: 6 months

    Description: Heartburn/regurgitation domain score from the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). The domain score is calculated as the mean of the completed items within the heartburn/regurgitation domain and ranges from 0 (none) to 5 (very severe). Higher scores indicate worse symptom severity.

    Time Frame: Day 0 ± 28 days (pre-intervention), Day 90 ± 28 days, Day 180 ± 28 days.

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

    Time frame: 6 months

    Description: Nausea/vomiting domain score from the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). The domain score is calculated as the mean of the completed items within the nausea/vomiting domain and ranges from 0 (none) to 5 (very severe). Higher scores indicate worse symptom severity.

    Time Frame: Day 0 ± 28 days (pre-intervention), Day 90 ± 28 days, Day 180 ± 28 days.

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

    Time frame: 6 months

    Description: Postprandial fullness/early satiety domain score from the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). The domain score is calculated as the mean of the completed items within the postprandial fullness/early satiety domain and ranges from 0 (none) to 5 (very severe). Higher scores indicate worse symptom severity.

    Time Frame: Day 0 ± 28 days (pre-intervention), Day 90 ± 28 days, Day 180 ± 28 days.

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

    Time frame: 6 months

    Description: Bloating domain score from the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). The domain score is calculated as the mean of the completed items within the bloating domain and ranges from 0 (none) to 5 (very severe). Higher scores indicate worse symptom severity.

    Time Frame: Day 0 ± 28 days (pre-intervention), Day 90 ± 28 days, Day 180 ± 28 days.

  6. Upper Abdominal Pain Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Upper Abdominal Pain Domain Score)

    Time frame: 6 months

    Description: Upper abdominal pain domain score from the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). The domain score is calculated as the mean of the completed items within the upper abdominal pain domain and ranges from 0 (none) to 5 (very severe). Higher scores indicate worse symptom severity.

    Time Frame: Day 0 ± 28 days (pre-intervention), Day 90 ± 28 days, Day 180 ± 28 days.

  7. Lower Abdominal Pain Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Lower Abdominal Pain Domain Score)

    Time frame: 6 months

    Description: Lower abdominal pain domain score from the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). The domain score is calculated as the mean of the completed items within the lower abdominal pain domain and ranges from 0 (none) to 5 (very severe). Higher scores indicate worse symptom severity.

    Time Frame: Day 0 ± 28 days (pre-intervention), Day 90 ± 28 days, Day 180 ± 28 days.

  8. Serum Vitamin A (Retinol) Concentration

    Time frame: 6 months

    How measured: Serum vitamin A (retinol) concentration measured in blood. Blood collected by venipuncture and analyzed by IU Health Pathology Laboratory and/or ARUP Laboratories. Results will be reported in milligrams per liter (mg/L).

    Time points: Day 180 ± 28 days.

    Unit of Measure: mg/L

  9. Serum 25-Hydroxyvitamin D [25(OH)D] Concentration

    Time frame: 6 months

    How measured: Serum 25-Hydroxyvitamin D [25(OH)D] concentration measured in blood. Blood collected by venipuncture and analyzed by IU Health Pathology Laboratory and/or ARUP Laboratories. Results will be reported in nanograms per milliliter (ng/mL).

    Time points: Day 180 ± 28 days.

    Unit of Measure: ng/mL

  10. Serum Vitamin E (Alpha-Tocopherol) Concentration

    Time frame: 6 months

    How measured: Serum Vitamin E (Alpha-Tocopherol) concentration measured in blood. Blood collected by venipuncture and analyzed by IU Health Pathology Laboratory and/or ARUP Laboratories. Results will be reported in milligrams per liter (mg/L).

    Time points: Day 180 ± 28 days.

    Unit of Measure: mg/L

  11. International Normalized Ratio (INR)

    Time frame: 6 months

    What is measured: International Normalized Ratio (INR), a standardized measure of blood coagulation.

    How measured: Blood collected by venipuncture and analyzed by IU Health Pathology Laboratory and/or ARUP Laboratories.

    Time points: Day 180 ± 28 days.

    Unit of Measure: Unitless ratio (INR).

  12. Fecal Elastase-1 (FE-1) Concentration

    Time frame: 6 months

    Description: Fecal elastase-1 (FE-1) concentration measured in stool as a marker of exocrine pancreatic function. Stool samples will be collected and analyzed by a certified clinical laboratory. Results will be reported in micrograms of elastase per gram of stool (µg/g stool). Higher values indicate better exocrine pancreatic function.

    Time Frame: Day 0 ± 28 days (pre-intervention) and Day 180 ± 28 days.

    Unit of Measure: µg/g stool

  13. Sustainability of Pancreatic Sufficiency

    Time frame: 6 months

    Description: Maintenance of pancreatic sufficiency from baseline through Day 180, defined as fecal elastase-1 (FE-1) concentration greater than 200 µg/g stool at both baseline and Day 180. The outcome will be reported as the proportion of participants who remain pancreatic sufficient throughout the study period.

    Time Frame: Day 0 ± 28 days (pre-intervention), Day 180 ± 28 days

    Unit of Measure: Percent of participants maintaining pancreatic sufficiency

Sponsors and collaborators

Lead sponsor

Indiana University

Other

Collaborators

  • Indiana Clinical and Translational Sciences Institute

Registry information

Official study title

The Return of the Pancreas: Evaluating Impact of CFTR Modulators on Pancreatic Function

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Jun 8, 2026
Registry last updated
Jul 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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