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

NCT ID: NCT03551691

Last Updated: 2024-04-30

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-07

Study Completion Date

2022-11-02

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.

Conditions

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Pancreatic Insufficiency Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Omeprazole

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

Group Type ACTIVE_COMPARATOR

Omeprazole 20mg Capsule

Intervention Type DRUG

Omeprazole 20mg daily for 28 days

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type DRUG

Identically-appearing capsule to omeprazole for 28 days

Interventions

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Omeprazole 20mg Capsule

Omeprazole 20mg daily for 28 days

Intervention Type DRUG

Placebo oral capsule

Identically-appearing capsule to omeprazole for 28 days

Intervention Type DRUG

Other Intervention Names

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PPI Placebo

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
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chiesi USA, Inc.

INDUSTRY

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Virginia A Stallings, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

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Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 7472816 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27546383 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23357842 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25689042 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23629618 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8420740 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1984743 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 13680386 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 423042 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1505293 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7380201 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3885675 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8333766 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12142815 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25019293 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22513912 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12804466 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23748712 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22592630 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15343184 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17255835 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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17-014666

Identifier Type: -

Identifier Source: org_study_id

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