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

NCT ID: NCT05005793

Last Updated: 2025-05-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-01
• Study Completion Date: 2026-08-31

Brief 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.

Conditions

Metabolic Acidosis; Kidney Transplant; Complications; Vascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sodium bicarbonate

Oral sodium bicarbonate at a dose of 0.5 mEq/kg-lean body weight/day

Group Type: EXPERIMENTAL

Sodium bicarbonate

Intervention Type: DRUG

Oral sodium bicarbonate at 0.5 mEq/kg-lean body weight/day

Placebo

Oral placebo at a dose of 0.5 mEq/kg-lean body weight/day

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo at 0.5 mEq/kg-lean body weight/day

Interventions

Sodium bicarbonate

Oral sodium bicarbonate at 0.5 mEq/kg-lean body weight/day

Intervention Type: DRUG

Placebo

Placebo at 0.5 mEq/kg-lean body weight/day

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jessica Kendrick, MD MPH

Role: PRINCIPAL_INVESTIGATOR

University of Colorado Denver | Anschutz

Locations

University of Colorado

Aurora, Colorado, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jessica Kendrick, MD MPH

Role: CONTACT

jessica.kendrick@ucdenver.edu

3037244837

Facility Contacts

Jessica Kendrick

Role: primary

jessica.kendrick@cuanschutz.edu

303-724-4837

Other Identifiers

R01DK130255

Identifier Type: NIH

Identifier Source: secondary_id

View Link

21-3447

Identifier Type: -

Identifier Source: org_study_id