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

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Dysfunction; Chronic Kidney Disease; Metabolic Acidosis
• Intervention / Treatment: Drug: Placebo; Drug: Sodium Bicarbonate Tablets

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo medication will be used at a dose of 0.5 mEq/kg-lean body weight/day	Drug: Placebo; Participants will be given placebo at 0.5 mEq/kg-LBW/day for 12 months
Experimental: Sodium bicarbonate; Sodium bicarbonate will be used at a dose of 0.5 mEq/kg-lean body weight/day.	Drug: Sodium Bicarbonate Tablets; Participants will be given sodium bicarbonate at 0.5 mEq/kg-LBW/day for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cognitive Function Composite Score at 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.	Baseline and 12 months
Change in Fluid Cognition Composite Score at 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	baseline and 12 months
Change in Crystallized Cognition Composite Score at 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.	baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cerebrovascular Reactivity at 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).	Baseline and 12 months
Percent Change in Mean Blood Flow Velocity of the Middle Cerebral Artery at 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	Baseline and 12 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): August 30, 2023
• Study Completion (Actual): August 30, 2023

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 23, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Mental Disorders; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Neurocognitive Disorders; Cognition Disorders; Renal Insufficiency; Acid-Base Imbalance; Cognitive Dysfunction; Kidney Diseases; Renal Insufficiency, Chronic; Acidosis
• Other Study ID Numbers: 20-1672; R21AG068657 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: At the conclusion of the study, data, which has been stripped of all personal identification information and coded with a number, will be made available to qualified individuals within the scientific community who apply for data use. The results and outcomes of this study will be made generally available by publication and journal articles submitted to PubMed Central in compliance with NIH access guidelines.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No