Chronic Kidney Disease
Conditions
Brief summary
The purpose of this study is to determine if Rifaximin decreases serum and urine levels of bacterial byproducts and inflammatory markers in patients with chronic kidney disease and to evaluate changes in the bacterial content of the stool from these individuals.
Interventions
DRUGRifaximin
550mg pills
DRUGPlacebo
Placebo pill
Sponsors
Jason Stubbs, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic kidney disease with eGFR ≤ 39 ml/min/1.73m2
Exclusion criteria
* Patients with normal renal function or those with less advanced kidney disease * Inability or unwillingness to provide consent * Patients undergoing hemodialysis or peritoneal dialysis therapy or those who have undergone organ transplant * Patients who may be pregnant * Hemodynamically unstable patients * Patients with liver failure, pancreatic insufficiency, or inflammatory bowel disease * Patients with ongoing or recent infection and those with history of C-diff infection * Patients with abnormal bowel structure secondary to surgical or anatomic variations * Patients on certain medications including immunosuppressants, antidiarrheal agents, bile acid sequestrants and current or recent (within the last 3 months) use of antibiotics
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Serum Trimethylamine N-oxide (TMAO) | Change from baseline to Day 11 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| C-reactive Protein | Change from baseline to Day 11 | — |
| Change in Serum Interleukin-6 (IL-6) | Change from baseline to day 11 | post- minus pre-treatment values |
Countries
United States
Participant flow
Recruitment details
Recruitment period: June 2015 - January 2017
Participants by arm
| Arm | Count |
|---|---|
| Rifaximin Participants will receive a 10-day course of Rifaximin.
Rifaximin: 550mg PO BID | 17 |
| Placebo Participants will receive a 10-day course of placebo.
Placebo: Placebo PO BID | 14 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Acute illness, unrelated to study drug | 2 | 3 |
| Overall Study | Protocol Violation | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Rifaximin | Total |
|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 9 | 62 years STANDARD_DEVIATION 13 | 64 years STANDARD_DEVIATION 11 |
| Body mass index | 35 kg/m^2 STANDARD_DEVIATION 9 | 31 kg/m^2 STANDARD_DEVIATION 8 | 33 kg/m^2 STANDARD_DEVIATION 8 |
| Chronic kidney disease etiology Diabetes | 10 Participants | 4 Participants | 14 Participants |
| Chronic kidney disease etiology Glomerulonephritis | 0 Participants | 1 Participants | 1 Participants |
| Chronic kidney disease etiology Hypertension | 1 Participants | 4 Participants | 5 Participants |
| Chronic kidney disease etiology Other/unknown | 2 Participants | 8 Participants | 10 Participants |
| Chronic kidney disease etiology Polycystic kidney disease | 1 Participants | 0 Participants | 1 Participants |
| Diagnosis of diabetes | 11 Participants | 7 Participants | 18 Participants |
| Estimated glomerular filtration rate | 34.4 ml/min/1.73m^2 STANDARD_DEVIATION 14.2 | 27.9 ml/min/1.73m^2 STANDARD_DEVIATION 10.6 | 30.8 ml/min/1.73m^2 STANDARD_DEVIATION 12.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 14 Participants | 23 Participants |
| Serum C-reactive protein | 8.2 ug/ml STANDARD_DEVIATION 11.6 | 8.5 ug/ml STANDARD_DEVIATION 22.1 | 8.4 ug/ml STANDARD_DEVIATION 17.9 |
| Serum deoxycholic acid | 609.8 ng/ml STANDARD_DEVIATION 384.7 | 372.2 ng/ml STANDARD_DEVIATION 268.3 | 479.5 ng/ml STANDARD_DEVIATION 342 |
| Serum indoxyl sulfate | 2.3 ug/ml STANDARD_DEVIATION 0.8 | 3.7 ug/ml STANDARD_DEVIATION 2 | 3.1 ug/ml STANDARD_DEVIATION 1.8 |
| Serum Interleukin-6 | 3.3 pg/ml STANDARD_DEVIATION 2.6 | 2.1 pg/ml STANDARD_DEVIATION 1.6 | 2.7 pg/ml STANDARD_DEVIATION 2.2 |
| Serum kynurenic acid | 19.6 ng/ml STANDARD_DEVIATION 19 | 28.1 ng/ml STANDARD_DEVIATION 21.3 | 24.3 ng/ml STANDARD_DEVIATION 16.8 |
| Serum P-cresol sulfate | 14.4 ug/ml STANDARD_DEVIATION 4.7 | 18.5 ug/ml STANDARD_DEVIATION 10 | 16.7 ug/ml STANDARD_DEVIATION 8.2 |
| Serum Trimethylamine N-oxide | 15.6 uM STANDARD_DEVIATION 11.6 | 18.8 uM STANDARD_DEVIATION 18.7 | 17.3 uM STANDARD_DEVIATION 15.7 |
| Severity of Proteinuria Mild | 4 Participants | 4 Participants | 8 Participants |
| Severity of Proteinuria Moderate | 4 Participants | 7 Participants | 11 Participants |
| Severity of Proteinuria None | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 6 Participants | 11 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 14 |
| other Total, other adverse events | 1 / 17 | 2 / 14 |
| serious Total, serious adverse events | 0 / 17 | 0 / 14 |
Outcome results
Primary
Change in Serum Trimethylamine N-oxide (TMAO)
Time frame: Change from baseline to Day 11
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rifaximin | Change in Serum Trimethylamine N-oxide (TMAO) | -3.9 uM | Standard Deviation 15.4 |
| Placebo | Change in Serum Trimethylamine N-oxide (TMAO) | 0.5 uM | Standard Deviation 9.5 |
Secondary
Change in Serum Interleukin-6 (IL-6)
post- minus pre-treatment values
Time frame: Change from baseline to day 11
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rifaximin | Change in Serum Interleukin-6 (IL-6) | 0.3 pg/ml | Standard Deviation 1.1 |
| Placebo | Change in Serum Interleukin-6 (IL-6) | 0.8 pg/ml | Standard Deviation 2.1 |
Secondary
C-reactive Protein
Time frame: Change from baseline to Day 11
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rifaximin | C-reactive Protein | 6.0 ug/ml | Standard Deviation 19.7 |
| Placebo | C-reactive Protein | -2.6 ug/ml | Standard Deviation 5.8 |