Bicarbonate Administration in CKD

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Metabolic Acidosis
• Intervention / Treatment: Drug: Placebo; Drug: Sodium bicarbonate

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

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
Experimental: Sodium Bicarbonate; 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
Placebo Comparator: Placebo; 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

What is the study measuring?

Primary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Time Frame
Changes in Plasma Angiotensin II	Measured at baseline, 1, 6 and 12 months
Changes in Aldosterone	Measured at baseline, 1, 6 and 12 months
Changes in Endothelin-1	Measured at baseline, 1, 6 and 12 months
Change in Serum T50	Measured at baseline, 1, 6 and 12 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Jessica Kendrick, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2017
• Primary Completion (Actual): May 19, 2022
• Study Completion (Actual): May 19, 2022

Study Registration Dates

• First Submitted: September 23, 2016
• First Submitted That Met QC Criteria: September 23, 2016
• First Posted (Estimated): September 27, 2016

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: June 30, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Acid-Base Imbalance; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Acidosis
• Other Study ID Numbers: 16-1572

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.