Bicarbonate Administration in CKD

Study Overview
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Brief Summary
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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.

Official Title
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Bicarbonate Administration in CKD

Conditions
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Chronic Kidney Disease, Metabolic Acidosis

Intervention / Treatment
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* Drug: Sodium bicarbonate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium Bicarbonate<br>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. | Drug: Sodium bicarbonate<br> <br> |
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Left Ventricular Mass Index |  | Measured at baseline and 12 months |