The Impact of Proton Pump Inhibitors on the Fecal Microbiome

The Impact of Proton Pump Inhibitors on the Fecal Microbiome and Their Relationship to Clostridium Difficile Infection

The investigators hypothesis is that daily use of a proton pump inhibitor (PPI) is associated with significant alterations in the healthy fecal microbiome that are similar to those seen in persons with an initial episode of clostridium difficile infection (CDI).

Study Overview

• Status: Completed
• Conditions: Healthy; Clostridium Difficile Infection
• Intervention / Treatment: Drug: omeprazole

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Table 1. Inclusion Criteria for Healthy Volunteers:

1. Healthy individuals without chronic gastrointestinal problems or using antisecretory medications.

Table 2. Inclusion Criteria for Clostridium difficile infection subjects:

1. Newly diagnosed first episode of CDI prior to being treated.

Table 3. Exclusion Criteria for Healthy Subjects:

1. Prior gastrointestinal surgery that has altered the anatomy of the esophagus, stomach, or small/large intestine including appendectomy and cholecystectomy.
2. Chronic daily use of any medications that could alter gastrointestinal secretory or motor function (see Table 2).
3. Gastrointestinal, cardiovascular, endocrine, renal, or other chronic disease likely to affect gastrointestinal motility (e.g., uncontrolled diabetes mellitus).
4. Females of childbearing age who are not practicing at least one form of birth control at least one month prior to starting the PPI or are pregnant or lactating (a pregnancy test will be performed on female subjects prior to PPI use).
5. Significant untreated psychiatric disease.

Table 4. Prohibited Medications:

1. Antibiotics within 2 months of the stool sample collection.
2. Probiotics (e.g., Florastor, Align, Flora-Q, VSL#3, lactobacillus, bifidobacterium) within 2 weeks of the stool sample collection.
3. Fiber supplements (e.g., Metamucil, Citrucel, Benefiber), unless maintained on a stable dose for the last 3 months.
4. Chronic use of medications that alter gastric pH: proton pump inhibitors (e.g., omeprazole, lansoprazole, esomeprazole, pantoprazole, rabeprazole, dexlansoprazole) and histamine2 receptor antagonists (e.g., cimetidine, famotidine, ranitidine).
5. Chronic use of medications that affect gastrointestinal motility and/or transit including prokinetic agents (e.g., metoclopramide (Reglan), tegaserod (Zelnorm), domperidone (Motilium), erythromycin), narcotic analgesic agents (e.g., methadone, fentanyl, oxycodone, codeine, morphine, hydromorphone), laxatives including mineral oil, anticholinergic agents (e.g., Bentyl, Levsin), and antidiarrheal agents (e.g., Kaopectate (donnagel), Pepto-Bismol (bismuth subsalicylate), Imodium (loperamide), Lomotil (atropine with diphenoxylate), codeine, tincture of opium).

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

No Intervention: Proton pump inhibitor; We will recruit 10 healthy adult individuals and 5 adult patients with an initial episode of CDI cared for at Mayo Clinic in Arizona. A baseline stool sample will be collected from the healthy individuals. They will then be given a PPI, omeprazole 20 mg, to be taken once (n=5) or twice (n=5) daily for 1 month. Stool samples will be collected after 1 week and again after 1 month. A final stool sample will be collected 1 month after stopping the omeprazole. A stool sample will be collected from the CDI subjects before treatment of the infection and again 2 months after treatment to avoid enrolling those at risk for relapse (which most commonly occurs during the first 2 months after treatment).

Drug: omeprazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in fecal microbial diversity due to PPI therapy	2 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in fecal microbial diversity due to CDI	2 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: John Di Baise, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: March 26, 2013
• First Submitted That Met QC Criteria: April 2, 2013
• First Posted (Estimate): April 4, 2013

Study Record Updates

• Last Update Posted (Estimate): August 20, 2014
• Last Update Submitted That Met QC Criteria: August 18, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: proton pump inhibitor; gut microbiota; Clostridium difficile infection; Fecal microbiome; single episode of CDI
• Additional Relevant MeSH Terms: Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Clostridium Infections; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: 13-000180