Ignite Creation Date:
2024-05-06 @ 1:47 AM
Last Modification Date:
2024-10-26 @ 11:10 AM
Study NCT ID:
NCT01901276
Status:
COMPLETED
Last Update Posted:
2015-04-14
First Post:
2013-07-12
Brief Title:
Effects of Gastric Acid on Colonic Microbiome
Sponsor:
Daniel Freedberg
Organization:
Columbia University
Study Overview
Official Title:
The Effects of Gastric Acid Suppression on the Colonic Microbiome
Status:
COMPLETED
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None