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

Primary Purpose

Metabolic Acidosis, Kidney Transplant; Complications, Vascular Diseases

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Sodium bicarbonate

Placebo

About this trial

This is an interventional treatment trial for Metabolic Acidosis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of ColoradoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Sodium bicarbonate

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

Full Information

NCT ID

NCT05005793

First Posted

July 14, 2021

Last Updated

April 18, 2023

Sponsor

University of Colorado, Denver

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT05005793

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 1, 2021 (Actual)

Primary Completion Date

August 31, 2026 (Anticipated)

Study Completion Date

August 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Colorado, Denver

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metabolic Acidosis, Kidney Transplant; Complications, Vascular Diseases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Sodium bicarbonate

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Sodium bicarbonate

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in Brachial artery flow mediated dilation at 12 months

Description

Time Frame

Baseline and 12 months

Secondary Outcome Measure Information:

Title

Change in Large elastic artery stiffness and compliance at 12 months

Description

Time Frame

Baseline and 12 months

Title

Change in Tubular atrophy at 12 months

Description

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.

Time Frame

Baseline and 12 months

Title

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

Description

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.

Time Frame

Baseline and 12 months

Title

Change in interstitial fibrosis at 12 months

Description

Kidney transplant biopsies will be performed. Morphometric analysis will be performed using trichrome and Sirius Red to determine interstitial fibrosis.

Time Frame

Baseline and 12 months.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jessica Kendrick, MD MPH

Phone

3037244837

jessica.kendrick@ucdenver.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jessica Kendrick, MD MPH

Organizational Affiliation

University of Colorado Denver | Anschutz

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Colorado

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jessica Kendrick

Phone

303-724-4837

jessica.kendrick@cuanschutz.edu

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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.

IPD Sharing Time Frame

Learn more about this trial

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

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