This study proposes to: 1. Characterize the impact of oral vancomycin on C. difficile loads after end of treatment compared to a placebo group. 2. Determine the effect of oral vancomycin on structural and functional microbiome changes after end of treatment compared to a placebo group. 3. Characterize the impact of oral vancomycin against a placebo group on the daily frequency of loose stools by the end of treatment.
Clostridium difficile infection (CDI) is considered the most frequent healthcare associated infection in the US, causing almost half a million cases per year with an estimated annual cost of 4.8 billion dollars. Despite the existence of a few treatment options against CDI, yearly attributable deaths are estimated at 29,300 in the US. From April 2014 to April 2016, Froedtert Health reported 899 CDIs. Over half of these events are NAAT (Nucleic Acid Amplification Test)(+)/EIA (Enzyme immunoassay)(-) events. To test for CDI, NAAT followed by EIA is used in a Multistep algorithmic testing in which a sensitive nucleic acid amplification test (NAAT) is followed by a specific toxin A and toxin B enzyme immunoassay (EIA) and are among the most accurate methods for Clostridium difficile infection (CDI) diagnosis. There is currently uncertainty on how to treat these CDI events. The primary outcome of this randomized double blind controlled intervention trial will be changes in C. difficile (Clostridium difficile) loads between day 1 and day 14 and changes in C. difficile load between day 14 and day 28. Thirty patients with documented C. difficile will be randomized to either 14 days of vancomycin or placebo capsules. Block randomization will be used to assign patients to the treatment or placebo arms. Randomized assignments will be placed in sealed envelopes which will only be handled by the research pharmacist. Study related stool collections will be obtained on days 1, 7, 14, 21, and 28 (+/- 2days) \[Day 1=first day study drug was administered\]. Patients will be followed for 90 days starting on day 1. Patients unable to complete at least 7 days of study treatment will be removed from analysis and replaced.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
7
125 mg capsules every 6 hours for 14 days.
Gelatin pill manufactured to mimic 125 mg Vancomycin oral capsule
Medical College of Wisconsin, Inc.
Milwaukee, Wisconsin, United States
Determine the change in C. difficile loads between the vancomycin vs. placebo group.
Compare the impact of vancomycin vs placebo on changes in C. difficile load from stool samples collected on Day 1 to end-of-treatment (Day 14) and to Day 28 using quantitative Polymerase Chain Reaction (qPCR).
Time frame: Day 1- Day 28
Determine the long-term persistence of C. difficile from the change in qPCR levels between the vancomycin vs. placebo group
Establish the long-term persistence of C. difficile by qPCR from stool samples collected at Day 1, 7, 14, 21, 28, and 90 between the vancomycin and placebo group.
Time frame: Day 1 - Day 90
Characterize the change on structural alterations of the microbiome after end of treatment between the vancomycin vs. placebo groups through 16S rRNA sequencing.
Structural alterations of the microbiome after end of treatment will be determined using 16S rRNA sequencing from stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 \& 90. Structural alterations will be defined according to the Shannon Diversity Index.
Time frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in bile acids in the oral vancomycin vs. placebo groups by mass spectrometry.
Characterize the impact of oral vancomycin against placebo on functional microbiome changes after end of treatment by measuring bile acids. They will be measured via mass spectrometry using stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 \& 90.
Time frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in amino acids in the oral vancomycin vs. placebo groups by mass spectrometry.
Characterize the impact of oral vancomycin against placebo on functional microbiome changes after end of treatment by measuring amino acids. They will be measured via mass spectrometry using stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 \& 90.
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Time frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in sugars in the oral vancomycin vs. placebo groups by mass spectrometry.
Characterize the impact of oral vancomycin against placebo on functional microbiome changes after end of treatment by measuring sugars. They will be measured via mass spectrometry using stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 \& 90.
Time frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in lipids from Day 1 to Day 90 in the oral vancomycin vs. placebo groups by mass spectrometry.
Characterize the impact of oral vancomycin against placebo on functional microbiome changes after end of treatment by measuring lipids. They will be measured via mass spectrometry using stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 \& 90.
Time frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in frequency of bowel movements in the oral vancomycin vs. placebo groups.
Characterize the impact of oral vancomycin against a placebo group on the daily frequency of bowel movements by the end of treatment. This scale goes from 0 to \>20 in increments of 1. Data will be analyzed over time as a slope for each patient. The closer to 1 per 24 hours the better the outcome. Data will be obtained from patient self-reports using study questionnaires on Days 1, 7, 14, 21, 28 \& 90.
Time frame: Day 1 - Day 90 past the beginning of treatment