Proton Pump Inhibitors and Dysbiosis in Cirrhosis

The purpose of this study is to find out whether the use of medications that suppress acid in your stomach can change the composition of your bowel bacteria.

Study Overview

• Status: Completed
• Conditions: Healthy; Cirrhosis
• Intervention / Treatment: Drug: Omeprazole

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria for PPI initiation study:

• Cirrhosis not on current PPI or acid suppressive therapy
• No systemic antibiotics or probiotics

Exclusion Criteria for PPI initiation study:

• On systemic antibiotics
• On PPI or acid suppression therapy already
• unable to give informed consent
• Allergy to proton pump inhibitors

Inclusion Criteria for PPI withdrawal study:

• Cirrhosis on current PPI for an FDA-unapproved indication
• No systemic antibiotics or probiotics

Exclusion Criteria for PPI withdrawal study:

• On systemic absorbable antibiotics
• On PPI or acid suppression therapy for an FDA-approved indication
• unable to give informed consent
• unwilling to withdraw PPI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PPI inititation; Adding 40mg omeprazole QD for 14 days	Drug: Omeprazole; 20mg PO BID for 20 days
Active Comparator: PPI withdrawal; The intervention here is systematically withdrawing chronic PPI for 14 days	Drug: Omeprazole; 20mg PO BID for 20 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Overgrowth of Oral Microbiota in Their Stool After PPI Therapy Withdrawal or Initiation	Analysis at baseline will be compared to that at 2 weeks using Multitagged sequencing. Number of patients with overgrowth of oral microbiota in their stool after PPI therapy withdrawal or initiation were specifically analyzed.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Adverse Events During Initiation or Withdrawal of PPI Therapy	Analysis at baseline will be compared to that at 2 weeks. This will be specifically, changes in those with PPI withdrawal compared to those with PPI initiation	2 weeks

Collaborators and Investigators

• Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center

Publications and helpful links

General Publications

• Bajaj JS, Cox IJ, Betrapally NS, Heuman DM, Schubert ML, Ratneswaran M, Hylemon PB, White MB, Daita K, Noble NA, Sikaroodi M, Williams R, Crossey MM, Taylor-Robinson SD, Gillevet PM. Systems biology analysis of omeprazole therapy in cirrhosis demonstrates significant shifts in gut microbiota composition and function. Am J Physiol Gastrointest Liver Physiol. 2014 Nov 15;307(10):G951-7. doi: 10.1152/ajpgi.00268.2014. Epub 2014 Sep 25.
• Bajaj JS, Thacker LR, Fagan A, White MB, Gavis EA, Hylemon PB, Brown R, Acharya C, Heuman DM, Fuchs M, Dalmet S, Sikaroodi M, Gillevet PM. Gut microbial RNA and DNA analysis predicts hospitalizations in cirrhosis. JCI Insight. 2018 Mar 8;3(5):e98019. doi: 10.1172/jci.insight.98019.
• Bajaj JS, Liu EJ, Kheradman R, Fagan A, Heuman DM, White M, Gavis EA, Hylemon P, Sikaroodi M, Gillevet PM. Fungal dysbiosis in cirrhosis. Gut. 2018 Jun;67(6):1146-1154. doi: 10.1136/gutjnl-2016-313170. Epub 2017 Jun 3.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): February 1, 2018

Study Registration Dates

• First Submitted: October 21, 2011
• First Submitted That Met QC Criteria: October 24, 2011
• First Posted (Estimate): October 25, 2011

Study Record Updates

• Last Update Posted (Actual): March 19, 2018
• Last Update Submitted That Met QC Criteria: March 14, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: BAJAJ004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED