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

NCT04600323 | Completed Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: 20-1672R21AG068657
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolic Acidosis; Chronic Kidney Disease; Cognitive Dysfunction

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Change in Cerebrovascular Reactivity at 12 Months

  Baseline and 12 months

• Percent Change in Mean Blood Flow Velocity of the Middle Cerebral Artery at 12 Months

  Baseline and 12 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo medication will be used at a dose of 0.5 mEq/kg-lean body weight/day

Drug: Placebo

Sodium bicarbonate

EXPERIMENTAL

Sodium bicarbonate will be used at a dose of 0.5 mEq/kg-lean body weight/day.

Drug: Sodium Bicarbonate Tablets

Interventions

Sodium Bicarbonate Tablets DRUG

Participants will be given sodium bicarbonate at 0.5 mEq/kg-LBW/day for 12 months

Sodium bicarbonate

Placebo DRUG

Participants will be given placebo at 0.5 mEq/kg-LBW/day for 12 months

Placebo

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Related Publications (2)

• Gu F, You Z, Hawkins N, Reddin R, Hamour R, Shapiro A, Coughlan C, Seals D, Furgeson S, Dixon A, Nowak KL, Kendrick J. Effects of sodium bicarbonate therapy on cognitive and cerebrovascular function in midlife and older adults with chronic kidney disease: a pilot randomized trial. BMC Nephrol. 2025 Aug 12;26(1):454. doi: 10.1186/s12882-025-04388-6.

  PMID: 40797182 DERIVED

• Perez L, You Z, Kendrick J. Association of Plant-Based Protein Intake with Cognitive Function in Adults with CKD. Kidney360. 2023 Nov 1;4(11):1554-1561. doi: 10.34067/KID.0000000000000278. Epub 2023 Oct 27.

  PMID: 37889573 DERIVED

MeSH Terms

Conditions

Acidosis; Renal Insufficiency, Chronic; Cognitive Dysfunction

Interventions

Sodium Bicarbonate

Condition Hierarchy (Ancestors)

Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Bicarbonates; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Jessica Kendrick
• Organization: University of Colorado Denver

jessica.kendrick@cuanschutz.edu

3037244837

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2020
• First Posted: October 23, 2020
• Study Start: February 1, 2021
• Primary Completion: August 30, 2023
• Study Completion: August 30, 2023
• Last Updated: December 20, 2024
• Results First Posted: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• 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.

Locations

US (1)