Cystic Fibrosis (CF)Phase 4NCT07632768

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

A Phase 4 study testing Discontinuation of Pancreatic Enzyme Replacement Therapy in people with Cystic Fibrosis (CF) and Pancreatic Insufficiency, run by Indiana University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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: 1. Read more about this study

Who is it for?: Ages 0 to 18 years
Conditions the study is for: Cystic Fibrosis (CF), Pancreatic Insufficiency, Pancreas Disease
What is being tested?: Discontinuation of Pancreatic Enzyme Replacement Therapy
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 17 participants
Where: 1 siteUnited States
Study dates: 3 Dec 2024to 21 Jan 2026
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 0 to 18 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Riley Hospital for Children
Indianapolis, Indiana, 46202

Other trials in United States

About this study

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

Does discontinuation of PERT affect gastrointestinal symptoms, nutritional status, pancreatic function, or body composition over 6 months?
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

Read the detailed description

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.

Conditions: Cystic Fibrosis (CF), Pancreatic Insufficiency, Pancreas Disease, Exocrine Pancreatic Insufficiency, Exocrine Pancreatic Insufficiency in Subjects With Cystic Fibrosis, CFTR Gene Mutation
Being tested: Discontinuation of Pancreatic Enzyme Replacement Therapy
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
Medical subject headings: Cystic Fibrosis, Exocrine Pancreatic Insufficiency, Pancreatic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Discontinuation of Pancreatic Enzyme Replacement TherapyDrug
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.

Study groups in NCT07632768
Study group	Role	What they receive
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. Receives: Drug: Discontinuation of Pancreatic Enzyme Replacement Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: 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
Measured: 6 months

Secondary outcomes (13)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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).
Measured: 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
Measured: 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
Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Dec 202421 Jan 2026

First posted8 Jun 2026
Study start3 Dec 2024
Primary completion21 Jan 2026
Study completion21 Jan 2026

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (24)Papers the sponsor has linked to this study.
Other trials for Cystic Fibrosis (CF)Studies of the same condition, open and under way.
More trials run by Indiana UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07632768
Sponsor's protocol ID: 24152
Status last verified: Jun 2026
First submitted: 26 May 2026
Last updated: 2 Jul 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Deidentified individual participant data (IPD) that underlie the results reported in publications may be shared. Shared data may include demographic characteristics, growth parameters, gastrointestinal symptom questionnaire results, laboratory values, fecal elastase-1 results, body composition measurements, and pancreatic function outcomes collected during the study. Personally identifiable information will not be shared. Additional study documents, including the study protocol and statistical analysis plan, may be made available upon reasonable request and in accordance with institutional policies and participant consent.

Publications

Terlizzi V, Amato F, Castellani C, Ferrari B, Galietta LJV, Castaldo G, Taccetti G. Ex vivo model predicted in vivo efficacy of CFTR modulator therapy in a child with rare genotype. Mol Genet Genomic Med. 2021 Apr;9(4):e1656. doi: 10.1002/mgg3.1656. Epub 2021 Mar 13.
PubMed 33713579
Stephenson KG, Lingle AJ, Baumberger KA, Dellon EP, Esther CR Jr, Meier EM, Oermann CM, Shenoy VK, Smith NR, Wimmer NS, Duehlmeyer SR, Kam CW, McKinzie CJ, Poisson MO, Elson EC. Changes in fecal elastase-1 following initiation of CFTR modulator therapy in pediatric patients with cystic fibrosis. J Cyst Fibros. 2023 Nov;22(6):996-1001. doi: 10.1016/j.jcf.2023.09.005. Epub 2023 Sep 26.
PubMed 37758535
Stallings VA, Sainath N, Oberle M, Bertolaso C, Schall JI. Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations. J Pediatr. 2018 Oct;201:229-237.e4. doi: 10.1016/j.jpeds.2018.05.018. Epub 2018 Jul 18.
PubMed 30029855
Smith H, Rayment JH. Sustained recovery of exocrine pancreatic function in a teenager with cystic fibrosis treated with ivacaftor. Pediatr Pulmonol. 2020 Oct;55(10):2493-2494. doi: 10.1002/ppul.24952. Epub 2020 Jul 17. No abstract available.
PubMed 32678518
Schwarzenberg SJ, Vu PT, Skalland M, Hoffman LR, Pope C, Gelfond D, Narkewicz MR, Nichols DP, Heltshe SL, Donaldson SH, Frederick CA, Kelly A, Pittman JE, Ratjen F, Rosenfeld M, Sagel SD, Solomon GM, Stalvey MS, Clancy JP, Rowe SM, Freedman SD; Promise Study Group. Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI. J Cyst Fibros. 2023 Mar;22(2):282-289. doi: 10.1016/j.jcf.2022.10.003. Epub 2022 Oct 21.
PubMed 36280527
Rosenfeld M, Cunningham S, Harris WT, Lapey A, Regelmann WE, Sawicki GS, Southern KW, Chilvers M, Higgins M, Tian S, Cooke J, Davies JC; KLIMB study group. An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5 years (KLIMB). J Cyst Fibros. 2019 Nov;18(6):838-843. doi: 10.1016/j.jcf.2019.03.009. Epub 2019 Apr 30.
PubMed 31053538
Ronan NJ, Einarsson GG, Deane J, Fouhy F, Rea M, Hill C, Shanahan F, Elborn JS, Ross RP, McCarthy M, Murphy DM, Eustace JA, Mm T, Stanton C, Plant BJ. Modulation, microbiota and inflammation in the adult CF gut: A prospective study. J Cyst Fibros. 2022 Sep;21(5):837-843. doi: 10.1016/j.jcf.2022.06.002. Epub 2022 Jun 25.
PubMed 35764510
Ratjen F, Hug C, Marigowda G, Tian S, Huang X, Stanojevic S, Milla CE, Robinson PD, Waltz D, Davies JC; VX14-809-109 investigator group. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2017 Jul;5(7):557-567. doi: 10.1016/S2213-2600(17)30215-1. Epub 2017 Jun 9.
PubMed 28606620
Ramsey ML, Li SS, Lara LF, Gokun Y, Akshintala VS, Conwell DL, Heintz J, Kirkby SE, McCoy KS, Papachristou GI, Patel A, Singh VK, Hart PA. Cystic fibrosis transmembrane conductance regulator modulators and the exocrine pancreas: A scoping review. J Cyst Fibros. 2023 Mar;22(2):193-200. doi: 10.1016/j.jcf.2022.08.008. Epub 2022 Aug 23.
PubMed 36008229
Pope CE, Vo AT, Hayden HS, Weiss EJ, Durfey S, McNamara S, Ratjen A, Grogan B, Carter S, Nay L, Parsek MR, Singh PK, McKone EF, Aitken ML, Rosenfeld MR, Hoffman LR. Changes in fecal microbiota with CFTR modulator therapy: A pilot study. J Cyst Fibros. 2021 Sep;20(5):742-746. doi: 10.1016/j.jcf.2020.12.002. Epub 2020 Dec 31.
PubMed 33390317
Nichols AL, Davies JC, Jones D, Carr SB. Restoration of exocrine pancreatic function in older children with cystic fibrosis on ivacaftor. Paediatr Respir Rev. 2020 Sep;35:99-102. doi: 10.1016/j.prrv.2020.04.003. Epub 2020 Apr 14.
PubMed 32386958
Moshiree B, Freeman AJ, Vu PT, Khan U, Ufret-Vincenty C, Heltshe SL, Goss CH, Schwarzenberg SJ, Freedman SD, Borowitz D, Sathe M; GALAXY Study Group. Multicenter prospective study showing a high gastrointestinal symptom burden in cystic fibrosis. J Cyst Fibros. 2023 Mar;22(2):266-274. doi: 10.1016/j.jcf.2022.10.006. Epub 2022 Oct 29.
PubMed 36319569
Megalaa R, Gopalareddy V, Champion E, Goralski JL. Time for a gut check: Pancreatic sufficiency resulting from CFTR modulator use. Pediatr Pulmonol. 2019 Aug;54(8):E16-E18. doi: 10.1002/ppul.24353. Epub 2019 May 7.
PubMed 31066218
McNamara JJ, McColley SA, Marigowda G, Liu F, Tian S, Owen CA, Stiles D, Li C, Waltz D, Wang LT, Sawicki GS. Safety, pharmacokinetics, and pharmacodynamics of lumacaftor and ivacaftor combination therapy in children aged 2-5 years with cystic fibrosis homozygous for F508del-CFTR: an open-label phase 3 study. Lancet Respir Med. 2019 Apr;7(4):325-335. doi: 10.1016/S2213-2600(18)30460-0. Epub 2019 Jan 24.
PubMed 30686767
Hager ER, Quigg AM, Black MM, Coleman SM, Heeren T, Rose-Jacobs R, Cook JT, Ettinger de Cuba SA, Casey PH, Chilton M, Cutts DB, Meyers AF, Frank DA. Development and validity of a 2-item screen to identify families at risk for food insecurity. Pediatrics. 2010 Jul;126(1):e26-32. doi: 10.1542/peds.2009-3146.
PubMed 20595453

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Return of the Pancreas: Evaluating Impact of CFTR Modulators on Pancreatic Function
ClinicalTrials.gov ID: NCT07632768
Acronym / sponsor ID: 24152
Conditions: Cystic Fibrosis (CF), Pancreatic Insufficiency, Pancreas Disease, Exocrine Pancreatic Insufficiency, Exocrine Pancreatic Insufficiency in Subjects With Cystic Fibrosis, CFTR Gene Mutation
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
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: Indiana UniversityUniversity, hospital or other
Collaborators: Indiana Clinical and Translational Sciences Institute
Study start: 3 Dec 2024 (actual)
Primary completion: 21 Jan 2026 (actual)
Study completion: 21 Jan 2026 (actual)
First posted: 8 Jun 2026 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Does discontinuation of PERT affect gastrointestinal symptoms, nutritional status, pancreatic function, or body composition over 6 months?
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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Intervention: Discontinuation of Pancreatic Enzyme Replacement Therapy	Experimental	Drug: Discontinuation of Pancreatic Enzyme Replacement TherapyParticipants 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.

Who may qualify

Ages: 0 to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Discontinuation of Pancreatic Enzyme Replacement TherapyParticipants 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	Intervention: Discontinuation of Pancreatic Enzyme Replacement Therapy

Primary outcome

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
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
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

13 secondary outcomes

Gastrointestinal Symptom Severity Total Score (PAGI-SYM Total Score)
Time frame: 6 months
Heartburn/Regurgitation Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Heartburn/Regurgitation Domain Score)
Time frame: 6 months
Nausea/Vomiting Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Nausea/Vomiting Domain Score)
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)
Time frame: 6 months
Bloating Symptom Severity (Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index [PAGI-SYM] Bloating Domain Score)
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)
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)
Time frame: 6 months
Serum Vitamin A (Retinol) Concentration
Time frame: 6 months
Serum 25-Hydroxyvitamin D [25(OH)D] Concentration
Time frame: 6 months
Serum Vitamin E (Alpha-Tocopherol) Concentration
Time frame: 6 months
International Normalized Ratio (INR)
Time frame: 6 months
Fecal Elastase-1 (FE-1) Concentration
Time frame: 6 months
Sustainability of Pancreatic Sufficiency
Time frame: 6 months

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2026.
Background: PubMed 33713579Terlizzi V, Amato F, Castellani C, Ferrari B, Galietta LJV, Castaldo G, Taccetti G. Ex vivo model predicted in vivo efficacy of CFTR modulator therapy in a child with rare genotype. Mol Genet Genomic Med. 2021 Apr;9(4):e1656. doi: 10.1002/mgg3.1656. Epub 2021 Mar 13.
Background: PubMed 37758535Stephenson KG, Lingle AJ, Baumberger KA, Dellon EP, Esther CR Jr, Meier EM, Oermann CM, Shenoy VK, Smith NR, Wimmer NS, Duehlmeyer SR, Kam CW, McKinzie CJ, Poisson MO, Elson EC. Changes in fecal elastase-1 following initiation of CFTR modulator therapy in pediatric patients with cystic fibrosis. J Cyst Fibros. 2023 Nov;22(6):996-1001. doi: 10.1016/j.jcf.2023.09.005. Epub 2023 Sep 26.
Background: PubMed 30029855Stallings VA, Sainath N, Oberle M, Bertolaso C, Schall JI. Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations. J Pediatr. 2018 Oct;201:229-237.e4. doi: 10.1016/j.jpeds.2018.05.018. Epub 2018 Jul 18.
Background: PubMed 32678518Smith H, Rayment JH. Sustained recovery of exocrine pancreatic function in a teenager with cystic fibrosis treated with ivacaftor. Pediatr Pulmonol. 2020 Oct;55(10):2493-2494. doi: 10.1002/ppul.24952. Epub 2020 Jul 17. No abstract available.
Background: PubMed 36280527Schwarzenberg SJ, Vu PT, Skalland M, Hoffman LR, Pope C, Gelfond D, Narkewicz MR, Nichols DP, Heltshe SL, Donaldson SH, Frederick CA, Kelly A, Pittman JE, Ratjen F, Rosenfeld M, Sagel SD, Solomon GM, Stalvey MS, Clancy JP, Rowe SM, Freedman SD; Promise Study Group. Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI. J Cyst Fibros. 2023 Mar;22(2):282-289. doi: 10.1016/j.jcf.2022.10.003. Epub 2022 Oct 21.
Background: PubMed 31053538Rosenfeld M, Cunningham S, Harris WT, Lapey A, Regelmann WE, Sawicki GS, Southern KW, Chilvers M, Higgins M, Tian S, Cooke J, Davies JC; KLIMB study group. An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5 years (KLIMB). J Cyst Fibros. 2019 Nov;18(6):838-843. doi: 10.1016/j.jcf.2019.03.009. Epub 2019 Apr 30.
Background: PubMed 35764510Ronan NJ, Einarsson GG, Deane J, Fouhy F, Rea M, Hill C, Shanahan F, Elborn JS, Ross RP, McCarthy M, Murphy DM, Eustace JA, Mm T, Stanton C, Plant BJ. Modulation, microbiota and inflammation in the adult CF gut: A prospective study. J Cyst Fibros. 2022 Sep;21(5):837-843. doi: 10.1016/j.jcf.2022.06.002. Epub 2022 Jun 25.
Background: PubMed 28606620Ratjen F, Hug C, Marigowda G, Tian S, Huang X, Stanojevic S, Milla CE, Robinson PD, Waltz D, Davies JC; VX14-809-109 investigator group. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2017 Jul;5(7):557-567. doi: 10.1016/S2213-2600(17)30215-1. Epub 2017 Jun 9.
Background: PubMed 36008229Ramsey ML, Li SS, Lara LF, Gokun Y, Akshintala VS, Conwell DL, Heintz J, Kirkby SE, McCoy KS, Papachristou GI, Patel A, Singh VK, Hart PA. Cystic fibrosis transmembrane conductance regulator modulators and the exocrine pancreas: A scoping review. J Cyst Fibros. 2023 Mar;22(2):193-200. doi: 10.1016/j.jcf.2022.08.008. Epub 2022 Aug 23.
Background: PubMed 33390317Pope CE, Vo AT, Hayden HS, Weiss EJ, Durfey S, McNamara S, Ratjen A, Grogan B, Carter S, Nay L, Parsek MR, Singh PK, McKone EF, Aitken ML, Rosenfeld MR, Hoffman LR. Changes in fecal microbiota with CFTR modulator therapy: A pilot study. J Cyst Fibros. 2021 Sep;20(5):742-746. doi: 10.1016/j.jcf.2020.12.002. Epub 2020 Dec 31.
Background: PubMed 32386958Nichols AL, Davies JC, Jones D, Carr SB. Restoration of exocrine pancreatic function in older children with cystic fibrosis on ivacaftor. Paediatr Respir Rev. 2020 Sep;35:99-102. doi: 10.1016/j.prrv.2020.04.003. Epub 2020 Apr 14.
Background: PubMed 36319569Moshiree B, Freeman AJ, Vu PT, Khan U, Ufret-Vincenty C, Heltshe SL, Goss CH, Schwarzenberg SJ, Freedman SD, Borowitz D, Sathe M; GALAXY Study Group. Multicenter prospective study showing a high gastrointestinal symptom burden in cystic fibrosis. J Cyst Fibros. 2023 Mar;22(2):266-274. doi: 10.1016/j.jcf.2022.10.006. Epub 2022 Oct 29.
Individual participant dataSharing planned: Yes. Deidentified individual participant data (IPD) that underlie the results reported in publications may be shared. Shared data may include demographic characteristics, growth parameters, gastrointestinal symptom questionnaire results, laboratory values, fecal elastase-1 results, body composition measurements, and pancreatic function outcomes collected during the study. Personally identifiable information will not be shared. Additional study documents, including the study protocol and statistical analysis plan, may be made available upon reasonable request and in accordance with institutional policies and participant consent.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Body Mass Index (BMI) (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07632768, which also lists 24 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.