Effects of Gastric Acid on Colonic Microbiome

NCT ID: NCT01901276

Last Updated: 2024-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2015-03-31

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.

Detailed Description

Study Design We will recruit 12 adult volunteers for a crossover study with a total duration of 12 weeks. Subjects will be observed off of PPIs for 4 weeks and then will be placed on PPIs for 4 weeks. Subsequently, subjects will be randomized to receive an additional 4 weeks of PPIs or no therapy. Stool samples will be collected at 4 separate time points.

Study Outcomes and Statistical Analyses The primary outcome will be change in overall diversity of fecal flora after 4 weeks of PPIs compared to 4 weeks of no acid suppression. Additional outcomes to be assessed include the effect of PPIs on the relative abundance of Bacteroidetes at week 4 and change in the diversity of fecal flora at week 8.

Conditions

Clostridium Difficile

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Omeprazole 40 mg bid x 4-8 weeks

See study description for further details.

Group Type: EXPERIMENTAL

Omeprazole 40 mg bid

Intervention Type: DRUG

As above.

Interventions

Omeprazole 40 mg bid

As above.

Intervention Type: DRUG

Other Intervention Names

Brand name: Prilosec

Eligibility Criteria

Inclusion Criteria

• 18 or more years old
• Able to give informed consent

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Daniel Freedberg, MD

OTHER

Sponsor Role: lead

Responsible Party

Daniel Freedberg, MD

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Julian A Abrams, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University

New York, New York, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 26164495 (View on PubMed)

Other Identifiers

AAAL3307

Identifier Type: -

Identifier Source: org_study_id