End Stage Renal Disease
Conditions
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.
Interventions
DRUGVancomycin
Oral vancomycin 250mg capsules
OTHERPlacebo
Placebo Pills distributed by Research Pharmacy labeled placebo.
Sponsors
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Intervention model description
randomized double-blinded placebo-controlled crossover study
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo First or 250mg of Oral Vancomycin First (Crossover After 3 Months) Total cohort | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (3 Months) | Adverse Event | 1 | 0 |
| First Intervention (3 Months) | insufficient samples of plasma and stool | 4 | 0 |
Baseline characteristics
| Characteristic | Placebo First or 250mg of Oral Vancomycin First (Crossover After 3 Months) |
|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 9 |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black | 3 Participants |
| Race/Ethnicity, Customized Hispanic | 6 Participants |
| Race/Ethnicity, Customized Other or more than one | 2 Participants |
| Race/Ethnicity, Customized White | 2 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 5 |
| other Total, other adverse events | 0 / 10 | 0 / 5 |
| serious Total, serious adverse events | 0 / 10 | 0 / 5 |
Outcome results
Primary
Change in Plasma Concentration Measure of Indoxyl Sulphate (IS)
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 250mg of Oral Vancomycin First, Then Placebo | Change in Plasma Concentration Measure of Indoxyl Sulphate (IS) | -25.31 µM/ml | Standard Deviation 36.3 |
| Placebo First, Then 250mg of Oral Vancomycin | Change in Plasma Concentration Measure of Indoxyl Sulphate (IS) | 9.71 µM/ml | Standard Deviation 49.8 |
Primary
Change in Plasma Concentration Measure P-Cresyl Sulphate (PCS)
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 250mg of Oral Vancomycin First, Then Placebo | Change in Plasma Concentration Measure P-Cresyl Sulphate (PCS) | -73.51 µM/ml | Standard Deviation 127 |
| Placebo First, Then 250mg of Oral Vancomycin | Change in Plasma Concentration Measure P-Cresyl Sulphate (PCS) | 0.64 µM/ml | Standard Deviation 79.5 |