CardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients

Diabetes Mellitus, Type 2 Clinical Trial

— CREST-KT  

Official title:

CardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04906213
• Other study ID #: Pro00107752
• Status: Recruiting
• Phase: Phase 2
• Start date: July 25, 2022
• Est. completion date: August 2026

Study information

• Verified date: January 2024
• Source: Duke University
• Contact: Rachael Abuin, BSN
• Phone: 919-684 8136
• Email: rachael.abuin[@]duke.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: August 2026
• Est. primary completion date: July 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 -

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Kidney Transplant; Complications

Intervention

Drug:
• Empagliflozin10Mg Tab
Empagliflozin10 Mg daily or placebo daily for 18 months
• Placebo
10Mg Placebo Tab

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

References & Publications (6)

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):10 — View Citation

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(1 — View Citation

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: — View Citation

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. — View Citation

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 In — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events will be collected form the medical record and patient report		up to 18 months
Primary	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
Primary	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
Primary	Change in cardiac structure	Cardiac structure as measured by the 3D echocardiogram	Baseline, month 9 and month15
Primary	Change in blood insulin level	Blood insulin level will be determined lab values	Baseline, month 6 and month 18
Primary	Change in fasting blood sugar	Fasting Blood sugar will be determined lab values	Baseline, month 6 and month 18
Primary	Number of Urinary Tract infections	Data to be gathered from chart review and patient report	up to 18 months
Primary	Number of Genital infections	Data to be gathered from chart review and patient report	up to 18 months
Secondary	Change in kidney biopsy as measured by percentage of interstitial fibrosis		Baseline and 6 months
Secondary	Changes in Hemoglobin A1C as measured by blood work		Baseline, Months 3,6,9,12,15 and 18