The Effect of an Antibiotic on the Production of Uremic Toxins by the Gut Microbiome

Sponsor
NYU Langone Health (Other)
Overall Status
Completed
CT.gov ID
NCT03452189
Collaborator
(none)
15
1
2
8.7
1.7

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

Study Type:
Interventional
Actual Enrollment :
15 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
randomized double-blinded placebo-controlled crossover studyrandomized double-blinded placebo-controlled crossover study
Masking:
Double (Participant, Care Provider)
Primary Purpose:
Treatment
Official Title:
The Effect of an Antibiotic on the Production of Uremic Toxins by the Gut Microbiome
Actual Study Start Date :
Nov 27, 2017
Actual Primary Completion Date :
Aug 18, 2018
Actual Study Completion Date :
Aug 18, 2018

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:
  • vancomycin hydrochloride capsules
  • 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:
  • vancomycin hydrochloride capsules
  • Other: Placebo
    Placebo Pills distributed by Research Pharmacy labeled "placebo."

    Outcome Measures

    Primary Outcome Measures

    1. 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

    2. 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

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts 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.

    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.
    Responsible Party:
    NYU Langone Health
    ClinicalTrials.gov Identifier:
    NCT03452189
    Other Study ID Numbers:
    • 17-00963
    First Posted:
    Mar 2, 2018
    Last Update Posted:
    Mar 26, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    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

    1. Primary Outcome
    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)
    2. Primary Outcome
    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

    [Not Specified]

    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
    Email Jerome.Lowenstein@nyulangone.org
    Responsible Party:
    NYU Langone Health
    ClinicalTrials.gov Identifier:
    NCT03452189
    Other Study ID Numbers:
    • 17-00963
    First Posted:
    Mar 2, 2018
    Last Update Posted:
    Mar 26, 2021
    Last Verified:
    Mar 1, 2021