Clinical trial NCT04906213: CardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients
Official title: CardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Kidney Transplant; Complications
Diabetes Mellitus, Type 2
Keywords: Post operative kidney transplant
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2021-05-28
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo-controlled, double-blind, randomized clinical trial
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: 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 -

Primary outcomes:
measure: Change in kidney function as measured by eGFR
timeFrame: Baseline, 6 months, 9 months, 12 months and 18 months
measure: Change in kidney function as measured by albuminuria
timeFrame: Baseline, 6 months, 9 months, 12 months and 18 months
measure: Change in cardiac structure
timeFrame: Baseline, month 9 and month15
measure: Change in blood insulin level
timeFrame: Baseline, month 6 and month 18
measure: Change in fasting blood sugar
timeFrame: Baseline, month 6 and month 18
measure: Number of Urinary Tract infections
timeFrame: up to 18 months
measure: Number of Genital infections
timeFrame: up to 18 months
Secondary outcomes:
measure: Change in kidney biopsy as measured by percentage of interstitial fibrosis
timeFrame: Baseline and 6 months
measure: Changes in Hemoglobin A1C as measured by blood work
timeFrame: Baseline, Months 3,6,9,12,15 and 18
Other outcomes:
measure: Adverse events will be collected form the medical record and patient report
timeFrame: up to 18 months
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Myles Wolf, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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: 10.1056/NEJMoa1611925. Epub 2017 Jun 12.
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 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.
citation: 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.
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(10):752-72. doi: 10.1161/CIRCULATIONAHA.116.021887. Epub 2016 Jul 28.