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
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
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.
Riley Hospital for Children
Indianapolis, Indiana, United States
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
Time frame: 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
Time frame: 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
Time frame: 6 months
Gastrointestinal Symptom Severity Total Score (PAGI-SYM Total Score)
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.
Time frame: 6 months
Heartburn/Regurgitation Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Heartburn/Regurgitation Domain Score)
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.
Time frame: 6 months
Nausea/Vomiting Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Nausea/Vomiting Domain Score)
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.
Time frame: 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)
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.
Time frame: 6 months
Bloating Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Bloating Domain Score)
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.
Time frame: 6 months
Upper Abdominal Pain Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Upper Abdominal Pain Domain Score)
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.
Time frame: 6 months
Lower Abdominal Pain Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Lower Abdominal Pain Domain Score)
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.
Time frame: 6 months
Serum Vitamin A (Retinol) Concentration
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
Time frame: 6 months
Serum 25-Hydroxyvitamin D [25(OH)D] Concentration
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
Time frame: 6 months
Serum Vitamin E (Alpha-Tocopherol) Concentration
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
Time frame: 6 months
International Normalized Ratio (INR)
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).
Time frame: 6 months
Fecal Elastase-1 (FE-1) Concentration
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
Time frame: 6 months
Sustainability of Pancreatic Sufficiency
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
Time frame: 6 months
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