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

Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06140537
• Other study ID #: 23-1360
• Status: Recruiting
• Phase: Phase 4
• Start date: February 1, 2024
• Est. completion date: December 31, 2028

Study information

• Verified date: February 2024
• Source: University of Colorado, Denver
• Contact: Jessica Kendrick
• Phone: 3037244837
• Email: Jessica.Kendrick[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 31, 2028
• Est. primary completion date: October 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Kidney Transplant; Complications
• Vascular Diseases

Intervention

Drug:
• Dapagliflozin 10mg Tab
Dapagliflozin 10mg orally daily
• Placebo
Placebo one tablet orally daily

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

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