Effects of Gastric Acid on Colonic Microbiome

Clostridium Difficile Clinical Trial

Official title:

The Effects of Gastric Acid Suppression on the Colonic Microbiome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01901276
• Other study ID #: AAAL3307
• Status: Completed
• Phase: Phase 4
• First received: July 12, 2013
• Last updated: April 13, 2015
• Start date: August 2013
• Est. completion date: March 2015

Study information

• Verified date: April 2015
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Clostridium Difficile

Intervention

Drug:
• Omeprazole 40 mg bid
As above.

Locations

Country	Name	City	State
United States	Columbia University	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Daniel Freedberg

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Microbiome diversity	In order to assess the diversity of the colonic microbiome, three Bray-Curtis indices 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 0); After 8 weeks of twice daily PPI or four weeks of "washout" (Week 8 vs. Week 4)	4 weeks