Efficacy and Mechanisms of Dapagliflozin in Promoting Kidney Function and Cardiovascular Health in Kidney Transplant Recipients

Long-term allograft function in kidney transplant recipients (KTRs) remain suboptimal, and graft failure causes significant morbidity and mortality, with cardiovascular disease being the leading cause of death in KTRs and the most common cause of death with a functioning graft. Sodium-glucose cotransporter 2 (SGLT2) inhibitors safely lower cardiovascular and kidney disease risk in the non-transplant population, yet data in KTRs are lacking. This clinical trial seeks to establish the efficacy and safety of dapagliflozin, a SGLT2 inhibitor, for improving cardiovascular and kidney graft function in adult KTRs with type 2 diabetes and post-transplant diabetes, and to leverage innovate translational methods to define the underlying mechanisms of action.

Study Overview

• Status: Recruiting
• Conditions: Vascular Diseases; Diabetes; Kidney Transplant; Complications
• Intervention / Treatment: Drug: Dapagliflozin 10mg Tab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jessica Kendrick; Phone Number: 3037244837; Email: Jessica.Kendrick@cuanschutz.edu
• Study Contact Backup: Name: Petter Bjornstad; Email: petter.bjornstad@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz Medical Campus
      • Contact: Rachael Reddin; Email: Rachael.Reddin@cuanschutz.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-80 years
• Kidney transplant received 1 year prior to randomization
• estimated glomerular filtration rate 30-90 ml/min/1.73m2
• Urine albumin to creatinine ratio (ACR) 30-5000 mg/g
• Pre-existing type 2 diabetes or post-transplant diabetes mellitus
• Blood pressure <130/80 mm Hg prior to randomization
• Able to provide informed consent
• Stable immunosuppression for at least 3 months prior to baseline consisting of tacrolimus, mycophenolate mofetil/mycophenolic acid and prednisone
• Stable anti-hypertensive regimen for at least 1month prior to baseline
• Stable diabetes management for at least 3 months prior to baseline
• Stable angiotensin converting enzyme inhibitor/angiotensin receptor blocker use for at least 3 months prior to baseline (if applicable)
• Glucagon-like peptide-1 receptor agonist (GLP-1RA) for at least 3 months prior to baseline (if applicable)

Exclusion Criteria:

• Type 1 diabetes
• Anticipated life expectancy <1 year
• Uncontrolled hypertension
• Hemoglobin A1c >9%
• Body mass index >40 kg/m2
• New York Heart Association Class 3 or 4 heart failure symptoms, an EF ≤30%, or hospitalization for heart failure in the past 3 months
• Pregnancy, plans to become pregnant, or breastfeeding
• Current use of sodium glucose cotransporter-2 (SGLT2) inhibitors
• Current urinary or urogenital infection
• Use of anticoagulants (contraindication to kidney biopsy)
• Magnetic resonance imaging (MRI) contraindications
• History of lower-limb amputation irrespective of etiology
• Known hypersensitivity to dapagliflozin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; Participants will receive dapagliflozin 10mg daily	Drug: Dapagliflozin 10mg Tab; Dapagliflozin 10mg orally daily
Placebo Comparator: Placebo; Participants will receive one placebo tablet daily	Drug: Placebo; Placebo one tablet orally daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Albuminuria	Measured by urine albumin to creatinine ratio	Change from baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney oxygenation	Measured by MRI	Change from baseline to 12 months
Arterial stiffness	Measured by aortic pulse wave velocity	Change from baseline to 12 months
Kidney fibrosis	Measured by Magnetic Resonance Imaging (MRI) and kidney biopsy tissue	Change from baseline to 12 months
Left ventricular mass	measured by cardiac MRI	Change from baseline to 12 months
estimated glomerular filtration rate	estimated by CKD epi equation	Change from baseline to 12 months
Kidney morphometry, metabolomics from paired kidney biopsies	measured by single cell RNA sequencing from paired kidney biopsies	Change from baseline to 12 months
safety and tolerability	assessed on basis of adverse events	baseline, 6 and 12 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: November 14, 2023
• First Submitted That Met QC Criteria: November 14, 2023
• First Posted (Actual): November 20, 2023

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: 23-1360

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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: 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 Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes