CardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients (CREST-KT)

CREST-KT is a single-center, double-blinded, randomized trial of empagliflozin therapy in 72 kidney transplant recipients with (n=36) and without type 2 diabetes (n=36). After evenly dividing patients by type 2 diabetes diagnosis, patients will be randomized 2:1 to empagliflozin 10mg versus placebo.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2; Kidney Transplant; Complications
• Intervention / Treatment: Drug: Empagliflozin10Mg Tab; Drug: Placebo

Detailed Description

A screening visit will occur at which time an informed consent will be obtained, and eligibility determined. Women of childbearing potential will have a serum pregnancy test performed. This will be followed by a baseline visit. A renal biopsy and a 3D echocardiogram will be performed. At the next visit randomization will be performed and the subjects will receive their study medication, either empagliflozin or a placebo. Following the randomization visit the subject will return every 3 months (visits 2-7) for a total of 6 visits spanning 18 months. At each visit vital signs and weight will be taken. Other procedures include labs drawn for hematology, basic chemistry, coagulation, Glycated hemoglobin and serum insulin. A 3 D echocardiogram is repeated on Visits 4 and 6. A renal biopsy is repeated on Visit 3.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rachael Abuin, BSN; Phone Number: 919-684 8136; Email: rachael.abuin@duke.edu
• Study Contact Backup: Name: Daniel Edmonston, MD; Phone Number: 919-668-4596; Email: daniel.edmonston@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Rachael Abuin, BSN; Phone Number: 919-684-8136; Email: rachael.abuin@duke.edu
      • Contact: Daniel Edmonston, MD; Phone Number: 919 668 4596; Email: Daniel.edmonston@duke.edu
      • Principal Investigator: Myles Wolf, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Equal to or greater than 12 months and up tp 60 months post kidney transplant
2. Estimated glomerular filtration rate (eGFR) equal to or greater than 30ml/min/1.73m squared at screening
3. Standard immunosuppression, including calcineurin inhibitor, Mycophenolate Mofetil or Sodium and a glucocorticoid
4. Able to provide written consent -

Exclusion Criteria:

1. Type I diabetes
2. Any other solid organ transplant
3. Hemoglobin A1c greater than 12 %
4. SGLT2i use at the time of enrollment
5. Prior SGLT2i allergy or intolerance
6. Pregnant or nursing at the time of enrollment
7. History of antibody medicated rejection (AMR) or a Banff score greater than 2B for acute cellular rejection (ACR)
8. Active anticoagulant use other than aspirin 81 mg for primary prevention of cardiovascular disease
9. Known positive donor-specific antibodies prior to enrollment
10. Uncircumcised men
11. Greater than 2 urinary tract infections (UTI) over the 12 months prior to enrollment
12. Any genital infections over the 12 months prior to enrollment -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I: With Type II Diabetes; Kidney Transplant recipient with Type II diabetes, randomized to either Empagliflozin or a placebo.	Drug: Empagliflozin10Mg Tab; Empagliflozin10 Mg daily or placebo daily for 18 months; Drug: Placebo; 10Mg Placebo Tab
Active Comparator: Arm 2: Without Diabetes; Kidney Transplant recipient without Type II diabetes, randomized to either Empagliflozin or a placebo	Drug: Empagliflozin10Mg Tab; Empagliflozin10 Mg daily or placebo daily for 18 months; Drug: Placebo; 10Mg Placebo Tab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in kidney function as measured by eGFR	eGFR will be measured by blood test	Baseline, 6 months, 9 months, 12 months and 18 months
Change in kidney function as measured by albuminuria	Albuminuria will be measured by urine Albumin/Creatinine Ratio	Baseline, 6 months, 9 months, 12 months and 18 months
Change in cardiac structure	Cardiac structure as measured by the 3D echocardiogram	Baseline, month 9 and month15
Change in blood insulin level	Blood insulin level will be determined lab values	Baseline, month 6 and month 18
Change in fasting blood sugar	Fasting Blood sugar will be determined lab values	Baseline, month 6 and month 18
Number of Urinary Tract infections	Data to be gathered from chart review and patient report	up to 18 months
Number of Genital infections	Data to be gathered from chart review and patient report	up to 18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in kidney biopsy as measured by percentage of interstitial fibrosis	Baseline and 6 months
Changes in Hemoglobin A1C as measured by blood work	Baseline, Months 3,6,9,12,15 and 18

Other Outcome Measures

Outcome Measure	Time Frame
Adverse events will be collected form the medical record and patient report	up to 18 months

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Myles Wolf, MD, Duke University

Publications and helpful links

General Publications

• Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Silverman MG, Zelniker TA, Kuder JF, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Ruff CT, Gause-Nilsson IAM, Fredriksson M, Johansson PA, Langkilde AM, Sabatine MS; DECLARE-TIMI 58 Investigators. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019 Jan 24;380(4):347-357. doi: 10.1056/NEJMoa1812389. Epub 2018 Nov 10.
• Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657. doi: 10.1056/NEJMoa1611925. Epub 2017 Jun 12.
• Stoumpos S, Jardine AG, Mark PB. Cardiovascular morbidity and mortality after kidney transplantation. Transpl Int. 2015 Jan;28(1):10-21. doi: 10.1111/tri.12413. Epub 2014 Aug 20.
• Zinman B, Lachin JM, Inzucchi SE. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2016 Mar 17;374(11):1094. doi: 10.1056/NEJMc1600827. No abstract available.
• Halden TAS, Kvitne KE, Midtvedt K, Rajakumar L, Robertsen I, Brox J, Bollerslev J, Hartmann A, Asberg A, Jenssen T. Efficacy and Safety of Empagliflozin in Renal Transplant Recipients With Posttransplant Diabetes Mellitus. Diabetes Care. 2019 Jun;42(6):1067-1074. doi: 10.2337/dc19-0093. Epub 2019 Mar 12.
• Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ. Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus: Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications. Circulation. 2016 Sep 6;134(10):752-72. doi: 10.1161/CIRCULATIONAHA.116.021887. Epub 2016 Jul 28.

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2022
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: May 18, 2021
• First Submitted That Met QC Criteria: May 24, 2021
• First Posted (Actual): May 28, 2021

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Post operative kidney transplant
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: Pro00107752

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual data will not be shared

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.: No