Chronic Kidney Disease, Metabolic Acidosis
Conditions
Brief summary
Low serum bicarbonate levels, even within the normal laboratory range, are strongly associated with increased risks of hypertension, endothelial dysfunction, cardiovascular disease and death. The current proposal will investigate whether bicarbonate administration in patients with chronic kidney disease (CKD) will improve the health and function of arteries and reduce the size of the left ventricle of the heart. Overall, the proposed research will provide important new scientific evidence upon which physicians can base recommendations to patients with CKD to decrease the risk of developing cardiovascular diseases.
Interventions
DRUGSodium bicarbonate
DRUGPlacebo
Sponsors
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 21 years * Serum bicarbonate 22-25 mEq/L on 2 separate measurements (at least 1 day apart) * CKD stage 3B or 4 at time of screening (eGFR 15-44 ml/min/1.73m2) * Blood pressure \<130/80 mm Hg prior to randomization * BMI \< 40 kg/m2 (FMD measurements can be inaccurate in severely obese patients). * Able to provide consent * Stable anti-hypertensive regimen for at least one month prior to randomization * Not taking medications that interact with agents administered during experimental sessions (e.g. sildenafil interacts with nitroglycerin).
Exclusion criteria
* Use of chronic daily oral alkali within the last 3 months (including sodium bicarbonate, calcium carbonate or baking soda) * Uncontrolled hypertension * Serum potassium \< 3.3 or ≥ 5.5 mEq/L at screening * New York Heart Association Class 3 or 4 heart failure symptoms, known EF ≤30%, or hospital admission for heart failure within the past 3 months * Factors judged to limit adherence to interventions * Anticipated initiation of dialysis or kidney transplantation within 12 months * Current participation in another research study * Pregnancy or planning to become pregnant or currently breastfeeding * Chronic use of supplemental oxygen * Use of immunosuppression in past 3 months * Metal implant or implanted electrical device (patient will be unable to get MRI)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Brachial Artery Flow Mediated Dilation | Measured at baseline and 12 months |
| Change in Aortic Pulse Wave Velocity | Measured at baseline,12 months |
Secondary
| Measure | Time frame |
|---|---|
| Change in Left Ventricular Mass Index | Measured at baseline and 12 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sodium Bicarbonate Participants assigned to oral sodium bicarbonate will receive 0.5 mEq/kg-lean body weight (LBW)/day for the entire 12 months. Participants will take ½ the daily dose in the morning and the other ½ in the evening. The number of capsules will be rounded to the nearest whole capsule. To reduce pill burden and increase compliance the maximum number of pills per day will be six.
Sodium bicarbonate | 55 |
| Placebo Subjects randomly assigned to placebo will take the same number of capsules as if they were assigned to receive 0.5 mEq/kg-LBW/day of sodium bicarbonate. Participants will take ½ the daily dose in the morning and the other ½ in the evening. The number of capsules will be rounded to the nearest whole capsule. To reduce pill burden and increase compliance the maximum number of pills per day will be six.
Placebo | 54 |
| Total | 109 |
Baseline characteristics
| Characteristic | Sodium Bicarbonate | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 60.8 years STANDARD_DEVIATION 12.5 | 62 years STANDARD_DEVIATION 12 | 62.6 years STANDARD_DEVIATION 10.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 13 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) White | 42 Participants | 86 Participants | 44 Participants |
| Region of Enrollment United States | 55 participants | 109 participants | 54 participants |
| Sex: Female, Male Female | 28 Participants | 55 Participants | 27 Participants |
| Sex: Female, Male Male | 27 Participants | 54 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 1 / 54 |
| other Total, other adverse events | 36 / 55 | 28 / 54 |
| serious Total, serious adverse events | 7 / 55 | 7 / 54 |
Outcome results
Primary
Change in Aortic Pulse Wave Velocity
Time frame: Measured at baseline,12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Bicarbonate | Change in Aortic Pulse Wave Velocity | Baseline | 998.3 cm/sec | Standard Deviation 447.5 |
| Sodium Bicarbonate | Change in Aortic Pulse Wave Velocity | 12 months | 1067.2 cm/sec | Standard Deviation 457.9 |
| Placebo | Change in Aortic Pulse Wave Velocity | Baseline | 994.8 cm/sec | Standard Deviation 373.5 |
| Placebo | Change in Aortic Pulse Wave Velocity | 12 months | 983.4 cm/sec | Standard Deviation 347.7 |
Primary
Change in Brachial Artery Flow Mediated Dilation
Time frame: Measured at baseline and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Bicarbonate | Change in Brachial Artery Flow Mediated Dilation | Baseline | 3.99 percentage | Standard Deviation 4.8 |
| Sodium Bicarbonate | Change in Brachial Artery Flow Mediated Dilation | 12 months | 4.25 percentage | Standard Deviation 3.51 |
| Placebo | Change in Brachial Artery Flow Mediated Dilation | Baseline | 3.78 percentage | Standard Deviation 4.3 |
| Placebo | Change in Brachial Artery Flow Mediated Dilation | 12 months | 4.43 percentage | Standard Deviation 3.9 |
Secondary
Change in Left Ventricular Mass Index
Time frame: Measured at baseline and 12 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sodium Bicarbonate | Change in Left Ventricular Mass Index | Baseline | 57.4 g/m2 |
| Sodium Bicarbonate | Change in Left Ventricular Mass Index | 12 months | 57.2 g/m2 |
| Placebo | Change in Left Ventricular Mass Index | Baseline | 59.4 g/m2 |
| Placebo | Change in Left Ventricular Mass Index | 12 months | 67.6 g/m2 |