Clinical trial NCT05005793: 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
Overall status: RECRUITING
Phase: PHASE4
Conditions: Metabolic Acidosis
Kidney Transplant; Complications
Vascular Diseases
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2021-08-16
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in Brachial artery flow mediated dilation at 12 months
timeFrame: Baseline and 12 months
Secondary outcomes:
measure: Change in Large elastic artery stiffness and compliance at 12 months
timeFrame: Baseline and 12 months
measure: Change in Tubular atrophy at 12 months
timeFrame: Baseline and 12 months
measure: Change in participant plasma and urine complement activation fragment levels at 12 months
timeFrame: Baseline and 12 months
measure: Change in interstitial fibrosis at 12 months
timeFrame: Baseline and 12 months.
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
Study officials:
affiliation: University of Colorado Denver | Anschutz
name: Jessica Kendrick, MD MPH
role: PRINCIPAL_INVESTIGATOR
References: