Chronic Kidney Disease, End Stage Renal Disease
Conditions
Brief summary
This study will determine the efficacy of diuretics in patients with chronic kidney disease.
Detailed description
Participants with chronic kidney disease will undergo two 1-week study periods (single-dose diuretic versus single-dose placebo) separated by 1-2 weeks of washout in a cross-over design. Blood and urine samples will be collected at the end of each study period to determine the effect on urine output and to assess the kidney clearance and levels of uremic solute. Participants will weigh themselves daily.
Interventions
DRUGMetolazone
Participants receive a single dose of metolazone.
DRUGPlacebo
Participants receive a single dose of placebo to match metolazone.
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* stable chronic kidney disease patients able to provide consent * stable dialysis patients who produce urine and able to provide consent
Exclusion criteria
* use of antibiotics for last two months or expected antibiotic use * recent hospitalization or other event resulting in instability of food intake
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urine Output | Change from baseline urine output at 1 week for each study arm | Average volume of urine produced in 24 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kidney Clearance of Uremic Solutes | Kidney clearance of uremic solutes at 1 week for each study arm | Kidney clearance of uremic solutes in ml/min. |
| Change in Quality of Life Questionnaire Score | Change from baseline quality of life score at 1 week for each study arm | Kidney Disease Quality of Life 36 Questionnaire (KDQOL36) |
| Plasma Urea | Week 1 | — |
| Blood Pressure | Week 1 | — |
| Weight Change | Baseline, Week 1 | — |
Countries
United States
Participant flow
Pre-assignment details
17 participants signed informed consent, and 6 were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Metolazone Then Placebo Metolazone single dose taken orally during the first week, followed by washout of 1-2 weeks, then placebo single dose taken the following week. | 3 |
| Placebo Then Metolazone Placebo single dose taken orally during the first week, followed by washout of 1-2 weeks, then metolazone single dose taken the following week. | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Metolazone Then Placebo | Total | Placebo Then Metolazone |
|---|---|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 1.5 | 66 years STANDARD_DEVIATION 9 | 66 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 1 Participants |
| Region of Enrollment United States | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Change in Urine Output
Average volume of urine produced in 24 hours.
Time frame: Change from baseline urine output at 1 week for each study arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metolazone | Change in Urine Output | 809 mL/day | Standard Deviation 466 |
| Placebo | Change in Urine Output | 676 mL/day | Standard Deviation 487 |
Secondary
Blood Pressure
Time frame: Week 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metolazone | Blood Pressure | Systolic | 140 mmHg | Standard Deviation 25 |
| Metolazone | Blood Pressure | Diastolic | 77 mmHg | Standard Deviation 13 |
| Placebo | Blood Pressure | Systolic | 146 mmHg | Standard Deviation 18 |
| Placebo | Blood Pressure | Diastolic | 76 mmHg | Standard Deviation 12 |
Secondary
Change in Quality of Life Questionnaire Score
Kidney Disease Quality of Life 36 Questionnaire (KDQOL36)
Time frame: Change from baseline quality of life score at 1 week for each study arm
Population: Because the plan was to administer the intervention as a single dose, the investigators determined that the KDQOL should be removed from the study design because it is an evaluation used to assess changes over time. This decision was made prior to enrollment of any participants and was not administered to any study participants; however, the measure was not removed from the registration at that time.
Secondary
Kidney Clearance of Uremic Solutes
Kidney clearance of uremic solutes in ml/min.
Time frame: Kidney clearance of uremic solutes at 1 week for each study arm
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metolazone | Kidney Clearance of Uremic Solutes | P-Cresol sulfate | 15 mL/min | Standard Deviation 11 |
| Metolazone | Kidney Clearance of Uremic Solutes | Indoxyl sulfate | 34 mL/min | Standard Deviation 20 |
| Metolazone | Kidney Clearance of Uremic Solutes | Hippurate | 61 mL/min | Standard Deviation 48 |
| Metolazone | Kidney Clearance of Uremic Solutes | Phenylactyl glutamine | 14 mL/min | Standard Deviation 9 |
| Placebo | Kidney Clearance of Uremic Solutes | Phenylactyl glutamine | 9 mL/min | Standard Deviation 7 |
| Placebo | Kidney Clearance of Uremic Solutes | P-Cresol sulfate | 10 mL/min | Standard Deviation 8 |
| Placebo | Kidney Clearance of Uremic Solutes | Hippurate | 42 mL/min | Standard Deviation 29 |
| Placebo | Kidney Clearance of Uremic Solutes | Indoxyl sulfate | 22 mL/min | Standard Deviation 15 |
Secondary
Plasma Urea
Time frame: Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metolazone | Plasma Urea | 54 mg/dL | Standard Deviation 15 |
| Placebo | Plasma Urea | 54 mg/dL | Standard Deviation 13 |
Secondary
Weight Change
Time frame: Baseline, Week 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metolazone | Weight Change | Baseline | 74 kg | Standard Deviation 30 |
| Metolazone | Weight Change | Week 1 | 1.6 kg | Standard Deviation 1.7 |
| Placebo | Weight Change | Week 1 | 1.9 kg | Standard Deviation 1.7 |
| Placebo | Weight Change | Baseline | 73 kg | Standard Deviation 31 |