Proton Pump Inhibitors (PPI) and Fat Absorption in Cystic Fibrosis (CF) and Exocrine Pancreatic Insufficiency (EPI)

Phase 2

Completed

• Conditions: Pancreatic Insufficiency; Cystic Fibrosis
• Interventions: Drug: Omeprazole 20mg Capsule; Drug: Placebo oral capsule

• Registration Number: NCT03551691
• Lead Sponsor: Children's Hospital of Philadelphia

Brief Summary

This is a clinical trial with a cross over design investigating the effect of the proton pump inhibitor omeprazole on fat malabsorption in subjects with cystic fibrosis and pancreatic insufficiency. Participants will be randomized to receive either omeprazole or placebo for 28 days, then cross over and receive omeprazole or placebo for another 28 days. Markers of fat absorption will be measured after each treatment course.

Detailed Description

Fat malabsorption contributes to poor nutritional status in people with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI). Prescribing gastric acid-reducing agents such as proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs) as an adjunct to pancreatic enzyme replacement therapy (PERT) to improve PERT efficacy and dietary fat absorption has become accepted clinical practice in CF, despite limited evidence to support the practice. Establishing the efficacy and true health benefit of acid suppression for nutritional status and outcomes in CF is particularly important in light of potential health risks and cost associated with long-term or even lifetime use of these medications.

This study aims to characterize changes in fat malabsorption using the coefficient of fat absorption (CFA) as the primary endpoint in subjects who are on and off acid suppression with a PPI in addition to PERT. Additionally, the SmartPill® will be used to evaluate duodenal power of hydrogen (pH) while on and off acid suppression, and the malabsorption blood test (MBT) will be used to characterize changes in fat absorption. Associations will be explored between changes in nutritional status (weight, height, BMI), clinical GI symptoms, and quality of life in subjects treated with PPI vs. placebo.

Study Timeline

• Study First Submitted: 2018-05-29
• Study First Submitted QC: 2018-05-29
• Study First Posted: 2018-06-11
• Study Start: 2018-08-07
• Primary Completion: 2022-11-02
• Study Completion: 2022-11-02
• Disposition First Submitted: 2023-10-30
• Results First Submitted: 2023-12-21
• Status Verified: 2024-04
• Results First Submitted QC: 2024-04-29
• Last Update Submitted: 2024-04-29
• Results First Posted: 2024-04-30
• Disposition First Posted: 2024-04-30
• Last Update Posted: 2024-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

• Cystic fibrosis and pancreatic insufficiency (Fecal elastase <200 ug/g stool)
• Age ≥12 years
• In usual state of good health
• Willing to participate in a four-month study with three visits

Exclusion Criteria

• Forced expiratory vital capacity at one second (FEV1) <40% predicted
• Pregnancy or breast feeding
• Other illness affecting growth or nutritional status
• Unwillingness to continue their clinically established PERT dose for the duration of the study
• Use of other medication that affects dietary fat absorption
• Allergy to soy products
• Allergy to safflower products
• For subjects ≥18 years, celiac disease or allergy to gluten

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Omeprazole	Omeprazole 20mg Capsule	Subjects will take omeprazole 20mg daily for 28 days, then undergo assessments of fat absorption.
Placebo	Placebo oral capsule	Subjects will take a placebo daily for 28 days, then undergo assessments of fat absorption.

Primary Outcome Measures

Name	Time	Method
Coefficient of Fat Absorption	After 28 days of treatment or placebo	Gold standard measurement of fat malabsorption

Secondary Outcome Measures

Name	Time	Method
Fat Absorption Via Malabsorption Blood Test	After 28 days of treatment or placebo	Measurement of serum pentadecanoic acid and heptadecanoic acid
Duodenal pH	After 28 days of treatment or placebo	Change in duodenal pH as measured by the motility testing system (SmartPill)

Trial Locations

Locations (1)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States