Bicarbonate Administration in Kidney Transplant Recipients

Not Applicable

Completed

• Conditions: Kidney Transplant; Complications; Metabolic Acidosis
• Interventions: Other: Placebo; Drug: Sodium Bicarbonate

• Registration Number: NCT03428464
• Lead Sponsor: University of Colorado, Denver

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-01-29
• Study First Submitted QC: 2018-02-08
• Study First Posted: 2018-02-09
• Study Start: 2018-12-05
• Primary Completion: 2020-03-25
• Study Completion: 2020-03-25
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-19
• Last Update Posted: 2020-10-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Sodium bicarbonate	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.

Primary Outcome Measures

Name	Time	Method
Change in Brachial Artery Flow-Mediated Dilation	Baseline, 8, 10, and 18 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change in Transforming Growth Factor Beta 1 (TGF-B1)	Baseline, 8, 10, and 18 weeks	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.
Change in Cognitive Function	Baseline, 8, 10, and 18 weeks	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.

Trial Locations

Locations (1)

University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States