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

NCT05005793 | Recruiting Phase 4 DMC

• 2 other identifiers: 21-3447R01DK130255
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change in Large elastic artery stiffness and compliance at 12 months

  Baseline and 12 months

• Change in Tubular atrophy at 12 months

  Baseline and 12 months

• Change in participant plasma and urine complement activation fragment levels at 12 months

  Baseline and 12 months

• Change in interstitial fibrosis at 12 months

  Baseline and 12 months.

Study Arms (2)

Sodium bicarbonate

EXPERIMENTAL

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

Drug: Sodium bicarbonate

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Sodium bicarbonate DRUG

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

Sodium bicarbonate

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Acidosis; Vascular Diseases

Interventions

Sodium Bicarbonate

Condition Hierarchy (Ancestors)

Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Bicarbonates; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Inorganic Chemicals; Sodium Compounds

Study Officials

• Jessica Kendrick, MD MPH

  University of Colorado Denver | Anschutz

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jessica Kendrick, MD MPH

CONTACT

3037244837; jessica.kendrick@ucdenver.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2021
• First Posted: August 16, 2021
• Study Start: December 1, 2021
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 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.

Locations

US (1)