Bicarbonate Administration and Cognitive Function in Midlife and Older Adults With CKD

Study Overview
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Brief Summary
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This is a pilot, randomized, double-blinded, placebo-controlled, 12-month trial of 50 patients with CKD stage 3b-4 with metabolic acidosis to examine the effect of sodium bicarbonate therapy on cognitive and cerebrovascular function.

Official Title
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Bicarbonate Administration and Cognitive Function in Midlife and Older Adults With CKD

Conditions
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Metabolic Acidosis, Chronic Kidney Disease, Cognitive Dysfunction

Intervention / Treatment
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* Drug: Sodium Bicarbonate Tablets
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50-75 years old Serum bicarbonate 16-22 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 Use of angiotensin converting enzyme inhibitor or angiotensin receptor blocker Stable anti-hypertensive regimen for at least one month prior to randomization Montreal Cognitive Assessment Score > 24 No history of stroke No history of dementia No history of neurologic disease Able to provide consent Exclusion Criteria:• Significant comorbid conditions that lead the investigator to conclude that life expectancy is less than 1 year 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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo medication will be used at a dose of 0.5 mEq/kg-lean body weight/day | Drug: Placebo<br>* Participants will be given placebo at 0.5 mEq/kg-LBW/day for 12 months<br>|
| Experimental: Sodium bicarbonate<br>Sodium bicarbonate will be used at a dose of 0.5 mEq/kg-lean body weight/day. | Drug: Sodium Bicarbonate Tablets<br>* Participants will be given sodium bicarbonate at 0.5 mEq/kg-LBW/day for 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cognitive Function at 12 months | Cognitive function will be determined using the NIH Toolbox-Cognition Battery computerized tests. Five major cognitive subdomains will be assessed including: 1)attention, 2)episodic memory, 3) working memory, 4) language, 5) executive function and 6)processing speed. The following summary scores will be recorded: Cognitive function composite score, Fluid cognition composite score and crystallized cognition composite score. | Baseline and 12 months | 
| Change in Cognitive Function composite score at 12 months | NIH Toolbox will be used to assess cognitive function composite score | baseline and 12 months | 
| Change in Fluid Cognition Composite Score at 12 months | NIH Toolbox will be used to assess fluid cognition composite score | baseline and 12 months | 
| Change in Crystallized cognition composite score at 12 months | NIH Toolbox will be used to assess crystallized cognition score | baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cerebrovascular hemodynamics at 12 months | Cerebrovascular reactivity will be measured using Transcranial Doppler US by assessing the change in mean blood flow velocity of the middle cerebral artery in response to a vasodilatory hypercapnia challenge. Cerebrovascular pulstatility index and resistance will be determined using the Gosling Pulsatility index. | Baseline and 12 months |