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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Pancreatic Insufficiency
• Intervention / Treatment: Drug: Omeprazole 40mg Capsule; Drug: Placebo oral capsule

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 Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19146
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: Chiesi USA, Inc.
• Investigators: Principal Investigator: Virginia A Stallings, MD, Children's Hospital of Philadelphia

Publications and helpful links

General Publications

• Borowitz DS, Grand RJ, Durie PR. Use of pancreatic enzyme supplements for patients with cystic fibrosis in the context of fibrosing colonopathy. Consensus Committee. J Pediatr. 1995 Nov;127(5):681-4. doi: 10.1016/s0022-3476(95)70153-2. No abstract available.
• Ng SM, Moore HS. Drug therapies for reducing gastric acidity in people with cystic fibrosis. Cochrane Database Syst Rev. 2016 Aug 22;2016(8):CD003424. doi: 10.1002/14651858.CD003424.pub4.
• Stallings VA, Mondick JT, Schall JI, Barrett JS, Wilson M, Mascarenhas MR. Diagnosing malabsorption with systemic lipid profiling: pharmacokinetics of pentadecanoic acid and triheptadecanoic acid following oral administration in healthy subjects and subjects with cystic fibrosis. Int J Clin Pharmacol Ther. 2013 Apr;51(4):263-73. doi: 10.5414/CP201793.
• Mascarenhas MR, Mondick J, Barrett JS, Wilson M, Stallings VA, Schall JI. Malabsorption blood test: Assessing fat absorption in patients with cystic fibrosis and pancreatic insufficiency. J Clin Pharmacol. 2015 Aug;55(8):854-65. doi: 10.1002/jcph.484. Epub 2015 Mar 23.
• Lightdale JR, Gremse DA; Section on Gastroenterology, Hepatology, and Nutrition. Gastroesophageal reflux: management guidance for the pediatrician. Pediatrics. 2013 May;131(5):e1684-95. doi: 10.1542/peds.2013-0421. Epub 2013 Apr 29.
• Heijerman HG, Lamers CB, Bakker W, Dijkman JH. Improvement of fecal fat excretion after addition of omeprazole to pancrease in cystic fibrosis is related to residual exocrine function of the pancreas. Dig Dis Sci. 1993 Jan;38(1):1-6. doi: 10.1007/BF01296765.
• Heijerman HG, Lamers CB, Bakker W. Omeprazole enhances the efficacy of pancreatin (pancrease) in cystic fibrosis. Ann Intern Med. 1991 Feb 1;114(3):200-1. doi: 10.7326/0003-4819-114-3-200.
• Proesmans M, De Boeck K. Omeprazole, a proton pump inhibitor, improves residual steatorrhoea in cystic fibrosis patients treated with high dose pancreatic enzymes. Eur J Pediatr. 2003 Nov;162(11):760-3. doi: 10.1007/s00431-003-1309-5. Epub 2003 Sep 17.
• Cox KL, Isenberg JN, Osher AB, Dooley RR. The effect of cimetidine on maldigestion in cystic fibrosis. J Pediatr. 1979 Mar;94(3):488-92. doi: 10.1016/s0022-3476(79)80609-5.
• Carroccio A, Pardo F, Montalto G, Iapichino L, Soresi M, Averna MR, Iacono G, Notarbartolo A. Use of famotidine in severe exocrine pancreatic insufficiency with persistent maldigestion on enzymatic replacement therapy. A long-term study in cystic fibrosis. Dig Dis Sci. 1992 Sep;37(9):1441-6. doi: 10.1007/BF01296016.
• Boyle BJ, Long WB, Balistreri WF, Widzer SJ, Huang N. Effect of cimetidine and pancreatic enzymes on serum and fecal bile acids and fat absorption in cystic fibrosis. Gastroenterology. 1980 May;78(5 Pt 1):950-3.
• Chalmers DM, Brown RC, Miller MG, Clarke PC, Kelleher J, Littlewood JM, Losowsky MS. The influence of long-term cimetidine as an adjuvant to pancreatic enzyme therapy in cystic fibrosis. Acta Paediatr Scand. 1985 Jan;74(1):114-7. doi: 10.1111/j.1651-2227.1985.tb10930.x.
• Bowler IM, Green JH, Wolfe SP, Littlewood JM. Resting energy expenditure and substrate oxidation rates in cystic fibrosis. Arch Dis Child. 1993 Jun;68(6):754-9. doi: 10.1136/adc.68.6.754.
• Francisco MP, Wagner MH, Sherman JM, Theriaque D, Bowser E, Novak DA. Ranitidine and omeprazole as adjuvant therapy to pancrelipase to improve fat absorption in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2002 Jul;35(1):79-83. doi: 10.1097/00005176-200207000-00017.
• Ng SM, Franchini AJ. Drug therapies for reducing gastric acidity in people with cystic fibrosis. Cochrane Database Syst Rev. 2014 Jul 13;(7):CD003424. doi: 10.1002/14651858.CD003424.pub3.
• Ng SM, Francini AJ. Drug therapies for reducing gastric acidity in people with cystic fibrosis. Cochrane Database Syst Rev. 2012 Apr 18;(4):CD003424. doi: 10.1002/14651858.CD003424.pub2.
• Ng SM, Jones AP. Drug therapies for reducing gastric acidity in people with cystic fibrosis. Cochrane Database Syst Rev. 2003;(2):CD003424. doi: 10.1002/14651858.CD003424.
• Kaunitz JD, Akiba Y. Wireless telemetry and cystic fibrosis: just the pHacts. Dig Dis Sci. 2013 Aug;58(8):2129-30. doi: 10.1007/s10620-013-2714-x. Epub 2013 Jun 9. No abstract available.
• Gelfond D, Ma C, Semler J, Borowitz D. Intestinal pH and gastrointestinal transit profiles in cystic fibrosis patients measured by wireless motility capsule. Dig Dis Sci. 2013 Aug;58(8):2275-81. doi: 10.1007/s10620-012-2209-1. Epub 2012 May 17.
• Borowitz D, Baker SS, Duffy L, Baker RD, Fitzpatrick L, Gyamfi J, Jarembek K. Use of fecal elastase-1 to classify pancreatic status in patients with cystic fibrosis. J Pediatr. 2004 Sep;145(3):322-6. doi: 10.1016/j.jpeds.2004.04.049.
• Borowitz D, Lin R, Baker SS. Comparison of monoclonal and polyclonal ELISAs for fecal elastase in patients with cystic fibrosis and pancreatic insufficiency. J Pediatr Gastroenterol Nutr. 2007 Feb;44(2):219-23. doi: 10.1097/MPG.0b013e31802c41de.

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2018
• Primary Completion (Actual): November 2, 2022
• Study Completion (Actual): November 2, 2022

Study Registration Dates

• First Submitted: May 29, 2018
• First Submitted That Met QC Criteria: May 29, 2018
• First Posted (Actual): June 11, 2018

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: fat absorption; pancreatic enzyme
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: 17-014666

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported will be shared upon request, after deidentification.
• IPD Sharing Time Frame: The data will be available immediately upon publication.
• IPD Sharing Access Criteria: Contact brownellj@email.chop.edu. Requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No