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

NCT03551691 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 17-014666
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Insufficiency; Cystic Fibrosis

Keywords

fat absorption; pancreatic enzyme

Outcome Measures

Primary Outcomes (1)

• Coefficient of Fat Absorption

  Gold standard measurement of fat malabsorption

  After 28 days of treatment or placebo

Secondary Outcomes (2)

• Duodenal pH

  After 28 days of treatment or placebo

• Fat Absorption Via Malabsorption Blood Test

  After 28 days of treatment or placebo

Study Arms (2)

Omeprazole

ACTIVE COMPARATOR

Subjects will take omeprazole 20mg daily for 28 days, then undergo assessments of fat absorption.

Drug: Omeprazole 20mg Capsule

Placebo

PLACEBO COMPARATOR

Subjects will take a placebo daily for 28 days, then undergo assessments of fat absorption.

Drug: Placebo oral capsule

Interventions

Omeprazole 20mg Capsule DRUG

Omeprazole 20mg daily for 28 days

Also known as: PPI

Omeprazole

Placebo oral capsule DRUG

Identically-appearing capsule to omeprazole for 28 days

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• Chiesi USA, Inc.: collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19146, United States

Location

Related Publications (21)

• 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.

  PMID: 7472816 BACKGROUND

• 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.

  PMID: 27546383 BACKGROUND

• 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.

  PMID: 23357842 BACKGROUND

• 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.

  PMID: 25689042 BACKGROUND

• 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.

  PMID: 23629618 BACKGROUND

• 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.

  PMID: 8420740 BACKGROUND

• 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.

  PMID: 1984743 BACKGROUND

• 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.

  PMID: 13680386 BACKGROUND

• 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.

  PMID: 423042 BACKGROUND

• 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.

  PMID: 1505293 BACKGROUND

• 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.

  PMID: 7380201 BACKGROUND

• 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.

  PMID: 3885675 BACKGROUND

• 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.

  PMID: 8333766 BACKGROUND

• 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.

  PMID: 12142815 BACKGROUND

• 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.

  PMID: 25019293 BACKGROUND

• 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.

  PMID: 22513912 BACKGROUND

• 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.

  PMID: 12804466 BACKGROUND

• 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.

  PMID: 23748712 BACKGROUND

• 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.

  PMID: 22592630 BACKGROUND

• 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.

  PMID: 15343184 BACKGROUND

• 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.

  PMID: 17255835 BACKGROUND

MeSH Terms

Conditions

Exocrine Pancreatic Insufficiency; Cystic Fibrosis

Interventions

Omeprazole

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Analysis of the secondary measures remains ongoing and results are anticipated in the Spring of 2024. Results from secondary outcomes will be reported when data analysis are complete.

Results Point of Contact

• Title: Dr. Virginia Stallings
• Organization: Children's Hospital of Philadelphia

stallingsv@chop.edu

267-425-1633

Study Officials

• Virginia A Stallings, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2018
• First Posted: June 11, 2018
• Study Start: August 7, 2018
• Primary Completion: November 2, 2022
• Study Completion: November 2, 2022
• Last Updated: April 30, 2024
• Results First Posted: April 30, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: The data will be available immediately upon publication.
• Access Criteria: Contact brownellj@email.chop.edu. Requestors will need to sign a data access agreement.

Locations

US (1)