Effects of Gastric Acid on Colonic Microbiome

NCT01901276 | Completed Phase 4 Results DMC

• 1 other identifier: AAAL3307
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The colonic microbiome is essential in human health and disease. Clostridium difficile-associated diarrhea (CDAD), a highly morbid form of infectious diarrhea, is caused by antibiotics which perturb the microbiome and allow C. difficile to proliferate. Proton pump inhibitors (PPIs) are powerful suppressors of gastric acid and among the most common medicines in the United States. Dozens of observational studies show that longterm PPI use is associated with CDAD. However, the mechanism by which PPIs cause CDAD is unknown. We believe that PPIs cause CDAD by inducing alterations in the human colonic microbiome. We will confirm or refute the hypothesized mechanism for the association between PPIs and CDAD using an unblinded, single-armed study design. We will use pyrosequencing of the hypervariable V4 region of the bacterial 16S ribosomal subunit gene in human fecal samples to describe the colonic flora. We will collect fecal samples from volunteers before and after PPIs given for different durations and test the microbiome to determine 1) whether PPIs diminish overall diversity, 2) whether PPIs diminish relative abundance of Bacteroidetes, 3) whether increased duration of PPIs affects diversity, and 4) whether there is recovery of diversity after completing a defined course of PPIs. We believe that PPIs will cause a pattern of diminished overall microbiome diversity and reduced anaerobes - the same pattern seen after use of antibiotics. Furthermore, we believe that increased PPI duration will further diminish diversity and that the microbiome will return to pre-PPI levels of diversity after PPIs are stopped. These results will facilitate biologically-based clinical interventions to reduce rates of CDAD among patients who require acid suppression.

Conditions

Clostridium Difficile

Keywords

Proton Pump Inhibitors; Microbiome; Clostridium difficile

Outcome Measures

Primary Outcomes (1)

• Shannon Diversity Index Measuring Change in Microbiome Diversity

  In order to assess the diversity of the colonic microbiome, the Shannon diversity index will be calculated for each subject: * After four weeks of no acid suppression (Week 0 vs. Week 4) * After four weeks of twice daily PPI (Week 4 vs. Week 8) The Shannon diversity index is a mathematical measure of species diversity in a given community. The Shannon index is calculated as: -∑\[(pi)×ln(pi)\] where H is the Shannon diversity index, and pi is the proportion of individuals of i-th species in a whole community. The minimum value of the Shannon diversity index is 0, which indicates there's no diversity - only one species is found in that habitat. There is no upper limit to the Shannon index. The higher the value of H, the higher the diversity of species in a particular community.

  Baseline (Week 0), Week 4, Week 8

Study Arms (1)

Omeprazole 40 mg bid x 4-8 weeks

EXPERIMENTAL

See study description for further details.

Drug: Omeprazole 40 mg bid

Interventions

Omeprazole 40 mg bid DRUG

As above.

Also known as: Brand name: Prilosec

Omeprazole 40 mg bid x 4-8 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• or more years old
• Able to give informed consent

You may not qualify if:

• Use of systemic antibiotics within the past year
• Use of acid suppression medications (PPIs or H2-receptor antagonists) within the past year (antacids permitted if more than one month from date of enrollment)
• History of chronic gastrointestinal mucosal disease (e.g. inflammatory bowel disease, celiac disease, microscopic colitis)
• Any clinically significant or uncontrolled major morbidity, including but not limited to serious cardiac or respiratory disease or uncontrolled HIV
• Abnormal bowel frequency (minimum once every 2 days, maximum 3 times per day)
• Use of clopidogrel or medications with potential significant interaction with PPIs
• Osteoperosis or history of non-traumatic bone fracture
• History of adverse reactions to PPIs
• Initiation of any new medication within the month prior to enrollment
• Pregnancy
• Inability to give informed consent

Sponsors & Collaborators

• Daniel Freedberg, MD: lead

Study Sites (1)

Columbia University

New York, New York, 10032, United States

Location

Related Publications (1)

• Freedberg DE, Toussaint NC, Chen SP, Ratner AJ, Whittier S, Wang TC, Wang HH, Abrams JA. Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial. Gastroenterology. 2015 Oct;149(4):883-5.e9. doi: 10.1053/j.gastro.2015.06.043. Epub 2015 Jul 9.

  PMID: 26164495 BACKGROUND

MeSH Terms

Interventions

Omeprazole; BID protein, human

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

Results Point of Contact

• Title: Daniel Freedberg, MD, MS
• Organization: Columbia University Medical Center

def2004@cumc.columbia.edu

212-305-1021

Study Officials

• Julian A Abrams, MD, MS

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 12, 2013
• First Posted: July 17, 2013
• Study Start: August 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: August 15, 2024
• Results First Posted: August 15, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)