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

Early Phase 1

Completed

• Conditions: Chronic Kidney Disease; Cognitive Dysfunction; Metabolic Acidosis
• Interventions: Drug: Placebo; Drug: Sodium Bicarbonate Tablets

• Registration Number: NCT04600323
• Lead Sponsor: University of Colorado, Denver

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-10-19
• Study First Submitted QC: 2020-10-19
• Study First Posted: 2020-10-23
• Study Start: 2021-02-01
• Primary Completion: 2023-08-30
• Study Completion: 2023-08-30
• Status Verified: 2024-12
• Results First Submitted: 2024-12-05
• Results First Submitted QC: 2024-12-18
• Last Update Submitted: 2024-12-18
• Results First Posted: 2024-12-20
• Last Update Posted: 2024-12-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo medication will be used at a dose of 0.5 mEq/kg-lean body weight/day
Sodium bicarbonate	Sodium Bicarbonate Tablets	Sodium bicarbonate will be used at a dose of 0.5 mEq/kg-lean body weight/day.

Primary Outcome Measures

Name	Time	Method
Change in Cognitive Function Composite Score at 12 Months	Baseline and 12 months	Cognitive function will be determined using the NIH Toolbox-Cognition Battery computerized tests. The Cognitive function composite score is based on the average of the Fluid and Crystallized composites. It is derived by averaging the Fluid and Crystallized standard scores, then deriving standard scores based on this new distribution. Fully Corrected T-scores are adjusted for for age, gender, race/ethnicity, and educational attainment. The score compares the score of the participant to those in the NIH Toolbox nationally representative normative sampling. The T-score has a mean of 50 in the general population and a SD of 10. Scores higher than the mean indicate better performance.
Change in Fluid Cognition Composite Score at 12 Months	baseline and 12 months	NIH Toolbox will be used to assess fluid cognition composite score. This score includes all the tests that are measuring fluid ability: Flanker, Dimensional Change, Picture sequence memory, list sorting and pattern comparison. The composite score is derived by averaging the standard scores of each of the measures. Fully Corrected T-scores are adjusted for age, gender, race/ethnicity, and educational attainment. The score compares the score of the participant to those in the NIH Toolbox nationally representative normative sampling. A fully corrected T-score at or near 50 (population mean with standard deviation of 10) indicates ability that is average compared with others nationally and one below 40 suggests the possibility of cognitive impairment. N
Change in Crystallized Cognition Composite Score at 12 Months	baseline and 12 months	NIH Toolbox will be used to assess crystallized cognition composite score. This composite score includes the picture vocabulary and reading tests. The composite score is derived by averaging the standard scores of each of the measure, and then driving standard scores based on this new distribution. Fully Corrected T-scores are adjusted for age, gender, race/ethnicity, and educational attainment. The score compares the score of the participant to those in the NIH Toolbox nationally representative normative sampling. A fully corrected T-score at or near 50 (population mean with standard deviation of 10) indicates ability that is average compared with others nationally as the mean T-score is 50 nationally. A score higher than 50 indicates better crystallized cognition.

Secondary Outcome Measures

Name	Time	Method
Change in Cerebrovascular Reactivity at 12 Months	Baseline and 12 months	Relative cerebrovascular reactivity was calculated as % change in mean blood flow velocity of the middle cerebral artery/(hypercapnia breath-by-breath end-tidal partial pressure of CO2 (ETCO2) minus resting ETCO2).
Percent Change in Mean Blood Flow Velocity of the Middle Cerebral Artery at 12 Months	Baseline and 12 months	Measured using Transcranial Doppler Ultrasonography in response to a vasodilatory hypercapnic challenge.The change in mean blood flow velocity of the middle cerebral artery (MVMCA) was computed as the difference between hypercapnic MVMCA and normocapnic MVMCA

Trial Locations

Locations (1)

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States