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

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06140537
• Collaborator: (none)
• Enrollment: 80
• Arms: 2
• Anticipated Duration (Months): 61

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant; Complications; Vascular Diseases; Diabetes	Drug: Dapagliflozin 10mg Tab; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Mechanisms of Dapagliflozin in Promoting Kidney Function and Cardiovascular Health in Kidney Transplant Recipients
• Anticipated Study Start Date: Dec 1, 2023
• Anticipated Primary Completion Date: Oct 31, 2028
• Anticipated Study Completion Date: Dec 31, 2028

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Albuminuria [Change from baseline to 12 months]

   Measured by urine albumin to creatinine ratio

Secondary Outcome Measures

1. Kidney fibrosis [Change from baseline to 12 months]

   Measured by MRI

2. Kidney oxygenation [Change from baseline to 12 months]

   Measured by MRI

3. Arterial stiffness [Change from baseline to 12 months]

   Measured by aortic pulse wave velocity

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18-80 years

• Kidney transplant received 1 year prior to randomization

• eGFR 30-90 ml/min/1.73m2

• UACR 30-5000 mg/g

• Pre-existing T2D 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 ACEi/ARB for at least 3 months prior to baseline (if applicable)

• 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

• NYHA 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 SGLT2i

• Current urinary or urogenital infection

• Use of anticoagulants (contraindication to kidney biopsy)

• MRI contraindications

• History of lower-limb amputation irrespective of etiology

• Known hypersensitivity to dapagliflozin

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT06140537
• Other Study ID Numbers: 23-1360
• First Posted: Nov 20, 2023
• Last Update Posted: Nov 20, 2023
• Last Verified: Nov 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Additional relevant MeSH terms: Vascular Diseases; Dapagliflozin

Study Results

No Results Posted as of Nov 20, 2023