The Effect of an Antibiotic on the Production of Uremic Toxins by the Gut Microbiome
Study Details
Study Description
Brief Summary
The purpose of this study is to determine if multiple doses of vancomycin over the course of 3 months will perturb the intestinal flora (microbiome) and result in reduced serum concentration of the uremic toxin indoxyl sulfate and p-cresyl sulfate. The design of the study will permit investigators to assess the variability of serum uremic retention solute concentrations with and without antibiotic over a three-month period.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: 250mg of oral vancomycin First After 3 months, initial experimental group will be switched to placebo for 3 months. |
Drug: Vancomycin
Oral vancomycin 250mg capsules
Other Names:
Other: Placebo
Placebo Pills distributed by Research Pharmacy labeled "placebo."
|
Placebo Comparator: Placebo First After three months, the control group will be crossed over to weekly oral vancomycin (250mg) |
Drug: Vancomycin
Oral vancomycin 250mg capsules
Other Names:
Other: Placebo
Placebo Pills distributed by Research Pharmacy labeled "placebo."
|
Outcome Measures
Primary Outcome Measures
- Change in Plasma Concentration Measure of Indoxyl Sulphate (IS) [4 weeks]
Plasma concentrations of IS were measured by HPLC (high pressure liquid chromatography). Assessed weekly between day 0 and Week 4; change from baseline/day 0 to Week 4 reported
- Change in Plasma Concentration Measure P-Cresyl Sulphate (PCS) [4 weeks]
Plasma concentrations of P-Cresyl Sulphate (PCS) were measured by HPLC (high pressure liquid chromatography) Assessed weekly between day 0 and Week 4; change from baseline/day 0 to Week 4 reported
Eligibility Criteria
Criteria
Inclusion Criteria:
- Patients with stable chronic kidney disease on hemodialysis with a fistula or an AV graft.
Exclusion Criteria:
-
Antibiotics received within the last 3 months;
-
recent diarrhea
-
known allergy to vancomycin
-
history of C. difficile infection
-
elevation of white blood cell count or fever within one week of enrollment.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | New York University School of Medicine | New York | New York | United States | 10016 |
Sponsors and Collaborators
- NYU Langone Health
Investigators
- Principal Investigator: Jerome Lowenstein, MD, NYU Langone Health
Study Documents (Full-Text)
More Information
Publications
None provided.- 17-00963
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | 250mg of Oral Vancomycin First, Then Placebo | Placebo First, Then 250mg of Oral Vancomycin |
---|---|---|
Arm/Group Description | 250mg of Oral Vancomycin given for 3 months then crossed over to placebo for additional 3 months (no washout period). | Placebo given for 3 months then crossed over to 250 mg of Oral Vancomycin for additional 3 months (no washout period). |
Period Title: First Intervention (3 Months) | ||
STARTED | 10 | 5 |
COMPLETED | 5 | 5 |
NOT COMPLETED | 5 | 0 |
Period Title: First Intervention (3 Months) | ||
STARTED | 5 | 5 |
COMPLETED | 5 | 5 |
NOT COMPLETED | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Placebo First or 250mg of Oral Vancomycin First (Crossover After 3 Months) |
---|---|
Arm/Group Description | Total cohort |
Overall Participants | 15 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
57.6
(9)
|
Sex: Female, Male (Count of Participants) | |
Female |
4
26.7%
|
Male |
11
73.3%
|
Race/Ethnicity, Customized (Count of Participants) | |
White |
2
13.3%
|
Black |
3
20%
|
Asian |
2
13.3%
|
Hispanic |
6
40%
|
Other or more than one |
2
13.3%
|
Outcome Measures
Title | Change in Plasma Concentration Measure of Indoxyl Sulphate (IS) |
---|---|
Description | Plasma concentrations of IS were measured by HPLC (high pressure liquid chromatography). Assessed weekly between day 0 and Week 4; change from baseline/day 0 to Week 4 reported |
Time Frame | 4 weeks |
Outcome Measure Data
Analysis Population Description |
---|
As there was no "washout period" following vancomycin, for the analysis of vancomycin effect, investigators compared the changes in solute levels in all 10 subjects while receiving vancomycin to the changes seen in the 5 "Z" series subjects while receiving placebo as the initial treatment. |
Arm/Group Title | 250mg of Oral Vancomycin First, Then Placebo | Placebo First, Then 250mg of Oral Vancomycin |
---|---|---|
Arm/Group Description | 250mg of Oral Vancomycin given for 3 months then crossed over to placebo for additional 3 months (no washout period). | Placebo given for 3 months then crossed over to 250 mg of Oral Vancomycin for additional 3 months (no washout period). |
Measure Participants | 10 | 5 |
Mean (Standard Deviation) [µM/ml] |
-25.31
(36.3)
|
9.71
(49.80)
|
Title | Change in Plasma Concentration Measure P-Cresyl Sulphate (PCS) |
---|---|
Description | Plasma concentrations of P-Cresyl Sulphate (PCS) were measured by HPLC (high pressure liquid chromatography) Assessed weekly between day 0 and Week 4; change from baseline/day 0 to Week 4 reported |
Time Frame | 4 weeks |
Outcome Measure Data
Analysis Population Description |
---|
As there was no "washout period" following vancomycin, for the analysis of vancomycin effect, investigators compared the changes in solute levels in all 10 subjects while receiving vancomycin to the changes seen in the 5 "Z" series subjects while receiving placebo as the initial treatment. |
Arm/Group Title | 250mg of Oral Vancomycin First, Then Placebo | Placebo First, Then 250mg of Oral Vancomycin |
---|---|---|
Arm/Group Description | 250mg of Oral Vancomycin given for 3 months then crossed over to placebo for additional 3 months (no washout period). | Placebo given for 3 months then crossed over to 250 mg of Oral Vancomycin for additional 3 months (no washout period). |
Measure Participants | 10 | 5 |
Mean (Standard Deviation) [µM/ml] |
-73.51
(127.00)
|
0.64
(79.50)
|
Adverse Events
Time Frame | 6 months | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | 250mg of Oral Vancomycin First | Placebo First | ||
Arm/Group Description | After 3 months, initial experimental group will be switched to placebo for 3 months. Vancomycin: Oral vancomycin 250mg capsules Placebo: Placebo Pills distributed by Research Pharmacy labeled "placebo." | After three months, the control group will be crossed over to weekly oral vancomycin (250mg) Vancomycin: Oral vancomycin 250mg capsules Placebo: Placebo Pills distributed by Research Pharmacy labeled "placebo." | ||
All Cause Mortality |
||||
250mg of Oral Vancomycin First | Placebo First | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/10 (0%) | 0/5 (0%) | ||
Serious Adverse Events |
||||
250mg of Oral Vancomycin First | Placebo First | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/10 (0%) | 0/5 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
250mg of Oral Vancomycin First | Placebo First | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/10 (0%) | 0/5 (0%) |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. Jerome Lowenstein |
---|---|
Organization | NYU Langone Health |
Phone | +1 212 263 5635 |
Jerome.Lowenstein@nyulangone.org |
- 17-00963