Bicarbonate Administration in Kidney Transplant Recipients

Metabolic acidosis is associated with vascular endothelial dysfunction and is a common complication in patients who have received a kidney transplant. Kidney transplant recipients (KTR) with lower serum bicarbonate levels, even within the normal range, have an increased risk of graft loss and mortality. The investigators propose a prospective, double-blind, randomized, placebo-controlled, 18-week crossover pilot study to examine the effects of sodium bicarbonate on vascular endothelial function, graft function, and cognitive function in 20 KTR patients.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant; Complications; Metabolic Acidosis
• Intervention / Treatment: Drug: Sodium Bicarbonate; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Kidney transplant received at least 1 year ago
• Serum bicarbonate 20-26 mEq/L on 2 separate measurements (at least 1 day apart)
• eGFR >45 ml/min/1.73m2
• Blood pressure <140/90 mm Hg prior to randomization
• BMI < 40 kg/m2 (FMD measurements can be inaccurate in severely obese patients).
• Able to provide consent
• Stable kidney transplant medication regimen for at least 1 month prior to randomization
• 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:

• 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
• 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: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sodium bicarbonate; During the treatment period, participants will receive 0.5 mEq/kg-lean body weight (LBW)/day of oral sodium bicarbonate for 8 weeks.	Drug: Sodium Bicarbonate; Participants will take ½ the daily dose of sodium bicarbonate in the morning and the other ½ in the evening.; Other Names: Baking soda
Placebo Comparator: Placebo; During the control period, participants will take the same number of placebo capsules as if they were assigned 0.5 mEq/kg-LBW/day of sodium bicarbonate.	Other: Placebo; Participants will take ½ the daily dose of a placebo in the morning and the other ½ in the evening.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brachial Artery Flow-Mediated Dilation	Brachial artery Flow-Mediated Dilation (FMD) will be determined using high-resolution ultrasonography (Toshiba Xario 200) as described originally by Celermajer et al., and more recently by our group. FMD will be measured at the beginning and end of each study period for a total of 4 measurements. ECG-gated end-diastolic ultrasound images and Doppler flow of the brachial artery will be acquired during baseline and FMD conditions.	Baseline, 8, 10, and 18 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Transforming Growth Factor Beta 1 (TGF-B1)	Urinary TGF-B1 will be measured from 24-hour urine collections. It will be measured by a commercially available ELISA (R&D Systems). The within day precision for this assay is 6.7% at 257 pg/ml. All measurements will be performed at the Children's Pediatric CTRC at Children's Hospital Colorado.	Baseline, 8, 10, and 18 weeks
Change in Cognitive Function	Cognitive function will be assessed using the National Institutes of Health (NIH) Toolbox computerized tests to evaluate 1) attention, 2) episodic memory, 3) working memory, 4) language, 5) executive function, and 6) processing speed.	Baseline, 8, 10, and 18 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2018
• Primary Completion (Actual): March 25, 2020
• Study Completion (Actual): March 25, 2020

Study Registration Dates

• First Submitted: January 29, 2018
• First Submitted That Met QC Criteria: February 8, 2018
• First Posted (Actual): February 9, 2018

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 19, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Acid-Base Imbalance; Acidosis
• Other Study ID Numbers: 17-2317

Drug and device information, study documents

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