Effect of Alkali Therapy on Vascular and Graft Function in Kidney Transplant Recipients

Vascular Diseases Clinical Trial

Official title:

Effect of Alkali Therapy on Vascular and Graft Function in Kidney Transplant

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05005793
• Other study ID #: 21-3447
• Secondary ID: R01DK130255
• Status: Recruiting
• Phase: Phase 4
• Start date: December 1, 2021
• Est. completion date: August 31, 2026

Study information

• Verified date: May 2024
• Source: University of Colorado, Denver
• Contact: Jessica Kendrick, MD MPH
• Phone: 3037244837
• Email: jessica.kendrick[@]ucdenver.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Lower serum bicarbonate levels, even within the normal laboratory range, in kidney transplant recipients (KTRs) are associated with an increased risk of graft loss, cardiovascular events and mortality. Because acid retention is common in KTRs, it is plausible that alkali therapy in KTRs may also result in improved vascular and graft function. The investigators will perform a randomized, double-blinded, placebo-controlled, 12 month study in 120 KTRs to examine the effect of sodium bicarbonate therapy on surrogate markers of CVD and graft function. The overall hypothesis is that treatment with bicarbonate will improve indicators of vascular and graft function in KTRs by decreasing complement activation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: August 31, 2026
• Est. primary completion date: August 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age 18-80 years

• Serum bicarbonate 16-24 mEq/L on 2 separate measurements (at least 1 day apart)

• Kidney transplant received 1 year prior to randomization

• eGFR = 45 ml/min/1.73m2 by CKD-EPI equation

• 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

• Immunosuppression regimen consisting of tacrolimus, mycophenolate mofetil and prednisone (95% of patients at University of Colorado are on this regimen)

• Stable immunosuppression regimen for at least three months 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

• Nephrotic range proteinuria (urine complement activation fragment measurements may not be accurate with severe proteinuria)

• 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

• Use of anticoagulants

Related Conditions & MeSH terms

• Acidosis
• Kidney Transplant; Complications
• Metabolic Acidosis
• Vascular Diseases

Intervention

Drug:
• Sodium bicarbonate
Oral sodium bicarbonate at 0.5 mEq/kg-lean body weight/day
• Placebo
Placebo at 0.5 mEq/kg-lean body weight/day

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Brachial artery flow mediated dilation at 12 months	Brachial artery FMD will be determined using high-resolution ultrasonographyECG-gated end-diastolic ultrasound images and Doppler flow of the brachial artery will be acquired during baseline and FMD conditions. For FMD, reactive hyperemia will be produced by inflating a pediatric BP cuff around the forearm to 250 mmHg for 5 minutes followed by rapid deflation.	Baseline and 12 months
Secondary	Change in Large elastic artery stiffness and compliance at 12 months	transcutaneous custom tonometers (Noninvasive hemodynamics Workstation, Cardiovascular Engineering Inc., Norwood, MA) will be positioned at the aorta and femoral artery to measure aortic pulse wave velocity.	Baseline and 12 months
Secondary	Change in Tubular atrophy at 12 months	Kidney transplant biopsies will be performed. Morphometric analysis will be performed using trichrome and Sirius Red to determine tubular atrophy. All imaging will be done using an Aperio scanner.	Baseline and 12 months
Secondary	Change in participant plasma and urine complement activation fragment levels at 12 months	Complement activation fragments (Ba, C4a, C3a, C5a, sC5b-9) will be measured at the University of Colorado Exsera Biolab located on the Anschutz Medical Campus.	Baseline and 12 months
Secondary	Change in interstitial fibrosis at 12 months	Kidney transplant biopsies will be performed. Morphometric analysis will be performed using trichrome and Sirius Red to determine interstitial fibrosis.	Baseline and 12 months.