Philadelphia, Pennsylvania 19146


Purpose:

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 summary:

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.


Criteria:

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 is Available At:


Original ID:

17-014666


NCT ID:

NCT03551691


Secondary ID:


Study Acronym:


Brief Title:

PPIs and Fat Absorption in CF and EPI


Official Title:

Proton Pump Inhibitors and Fat Absorption in Subjects With Cystic Fibrosis and Pancreatic Insufficiency


Overall Status:

Recruiting


Study Phase:

Phase 2


Genders:

N/A


Minimum Age:

12 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Children's Hospital of Philadelphia


Oversight Authority:

There was an error processing this request


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

24


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Virginia A Stallings, MD
Principal Investigator
Children's Hospital of Philadelphia
Primary Contact:Jefferson N Brownell, MD
2674251628
brownellj@email.chop.edu
Backup Contact:Joan I Schall, PhD
2674251632
schall@email.chop.edu

Study Dates

Start Date:August 7, 2018
Completion Date:June 30, 2020
Completion Type:Anticipated
Primary Completion Date:June 30, 2020
Primary Completion Type:Anticipated
Verification Date:March 2019
Last Changed Date:March 11, 2019
First Received Date:May 29, 2018

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Fat absorption via Malabsorption Blood Test
Time Frame:After 28 days of treatment or placebo
Safety Issues:False
Description:Measurement of serum pentadecanoic acid and heptadecanoic acid
Outcome Type:Secondary Outcome
Measure:Duodenal pH
Time Frame:After 28 days of treatment or placebo
Safety Issues:False
Description:Change in duodenal pH as measured by the SmartPill
Outcome Type:Primary Outcome
Measure:Coefficient of fat absorption
Time Frame:After 28 days of treatment or placebo
Safety Issues:False
Description:Gold standard measurement of fat malabsorption

Study Interventions

Intervention Type:Drug
Name:Omeprazole 40mg Capsule
Description:Omeprazole 40mg daily for 28 days
Arm Name:Treatment Arm
Intervention Type:Drug
Name:Placebo oral capsule
Description:Identically-appearing capsule to omeprazole
Arm Name:Placebo Arm

Study Arms

Study Arm Type:Active Comparator
Arm Name:Treatment Arm
Description:Subjects will take omeprazole 40mg daily for 28 days, then undergo assessments of fat absorption.
Study Arm Type:Placebo Comparator
Arm Name:Placebo Arm
Description:Subjects will take a placebo daily for 28 days, then undergo assessments of fat absorption.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Children's Hospital of Philadelphia
Agency Class:Industry
Agency Type:Collaborator
Agency Name:Chiesi Farmaceutici S.p.A.

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation: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. Review.
PMID:7472816
Reference Type:Reference
Citation:Ng SM, Moore HS. Drug therapies for reducing gastric acidity in people with cystic fibrosis. Cochrane Database Syst Rev. 2016 Aug 22;(8):CD003424. doi: 10.1002/14651858.CD003424.pub4. Review.
PMID:27546383
Reference Type:Reference
Citation: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
Reference Type:Reference
Citation: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
Reference Type:Reference
Citation: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. Review.
PMID:23629618
Reference Type:Reference
Citation: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.
PMID:8420740
Reference Type:Reference
Citation: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.
PMID:1984743
Reference Type:Reference
Citation: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. Epub 2003 Sep 17.
PMID:13680386
Reference Type:Reference
Citation: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.
PMID:423042
Reference Type:Reference
Citation: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.
PMID:1505293
Reference Type:Reference
Citation: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
Reference Type:Reference
Citation: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.
PMID:3885675
Reference Type:Reference
Citation: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.
PMID:8333766
Reference Type:Reference
Citation: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.
PMID:12142815
Reference Type:Reference
Citation: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. Review. Update in: Cochrane Database Syst Rev. 2016;8:CD003424.
PMID:25019293
Reference Type:Reference
Citation: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. Review. Update in: Cochrane Database Syst Rev. 2014;(7):CD003424.
PMID:22513912
Reference Type:Reference
Citation:Ng SM, Jones AP. Drug therapies for reducing gastric acidity in people with cystic fibrosis. Cochrane Database Syst Rev. 2003;(2):CD003424. Review. Update in: Cochrane Database Syst Rev. 2012;4:CD003424.
PMID:12804466
Reference Type:Reference
Citation: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.
PMID:23748712
Reference Type:Reference
Citation: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
Reference Type:Reference
Citation: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.
PMID:15343184
Reference Type:Reference
Citation: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.
PMID:17255835

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


If you would like to be contacted by the clinical trial representative please fill out the form below.