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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Pancreatic Insufficiency, Cystic Fibrosis

Intervention / Treatment
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* Drug: Omeprazole 40mg Capsule
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment Arm<br>Subjects will take omeprazole 40mg daily for 28 days, then undergo assessments of fat absorption. | Drug: Omeprazole 40mg Capsule<br>* Omeprazole 40mg daily for 28 days<br>|
| Placebo Comparator: Placebo Arm<br>Subjects will take a placebo daily for 28 days, then undergo assessments of fat absorption. | Drug: Placebo oral capsule<br>* Identically-appearing capsule to omeprazole for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coefficient of fat absorption | Gold standard measurement of fat malabsorption | After 28 days of treatment or placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duodenal pH | Change in duodenal pH as measured by the motility testing system (SmartPill) | After 28 days of treatment or placebo | 
| Fat absorption via Malabsorption Blood Test | Measurement of serum pentadecanoic acid and heptadecanoic acid | After 28 days of treatment or placebo | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fat absorption, pancreatic enzyme