Back to resultsCardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients (CREST-KT)
Primary Purpose
Kidney Transplant; Complications, Diabetes Mellitus, Type 2
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Empagliflozin10Mg Tab
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Kidney Transplant; Complications focused on measuring Post operative kidney transplant
Eligibility Criteria
Inclusion Criteria:
- Equal to or greater than 12 months and up tp 60 months post kidney transplant
- Estimated glomerular filtration rate (eGFR) equal to or greater than 30ml/min/1.73m squared at screening
- Standard immunosuppression, including calcineurin inhibitor, Mycophenolate Mofetil or Sodium and a glucocorticoid
- Able to provide written consent -
Exclusion Criteria:
- Type I diabetes
- Any other solid organ transplant
- Hemoglobin A1c greater than 12 %
- SGLT2i use at the time of enrollment
- Prior SGLT2i allergy or intolerance
- Pregnant or nursing at the time of enrollment
- History of antibody medicated rejection (AMR) or a Banff score greater than 2B for acute cellular rejection (ACR)
- Active anticoagulant use other than aspirin 81 mg for primary prevention of cardiovascular disease
- Known positive donor-specific antibodies prior to enrollment
- Uncircumcised men
- Greater than 2 urinary tract infections (UTI) over the 12 months prior to enrollment
- Any genital infections over the 12 months prior to enrollment -
Sites / Locations
- Duke University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Arm I: With Type II Diabetes
Arm 2: Without Diabetes
Arm Description
Kidney Transplant recipient with Type II diabetes, randomized to either Empagliflozin or a placebo.
Kidney Transplant recipient without Type II diabetes, randomized to either Empagliflozin or a placebo
Outcomes
Primary Outcome Measures
Change in kidney function as measured by eGFR
eGFR will be measured by blood test
Change in kidney function as measured by albuminuria
Albuminuria will be measured by urine Albumin/Creatinine Ratio
Change in cardiac structure
Cardiac structure as measured by the 3D echocardiogram
Change in blood insulin level
Blood insulin level will be determined lab values
Change in fasting blood sugar
Fasting Blood sugar will be determined lab values
Number of Urinary Tract infections
Data to be gathered from chart review and patient report
Number of Genital infections
Data to be gathered from chart review and patient report
Secondary Outcome Measures
Change in kidney biopsy as measured by percentage of interstitial fibrosis
Changes in Hemoglobin A1C as measured by blood work
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04906213
Brief Title
CardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients
Acronym
CREST-KT
Official Title
CardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 25, 2022 (Actual)
Primary Completion Date
July 31, 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Transplant; Complications, Diabetes Mellitus, Type 2
Keywords
Post operative kidney transplant
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Placebo-controlled, double-blind, randomized clinical trial
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
72 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm I: With Type II Diabetes
Arm Type
Active Comparator
Arm Description
Kidney Transplant recipient with Type II diabetes, randomized to either Empagliflozin or a placebo.
Arm Title
Arm 2: Without Diabetes
Arm Type
Active Comparator
Arm Description
Kidney Transplant recipient without Type II diabetes, randomized to either Empagliflozin or a placebo
Intervention Type
Drug
Intervention Name(s)
Empagliflozin10Mg Tab
Intervention Description
Empagliflozin10 Mg daily or placebo daily for 18 months
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
10Mg Placebo Tab
Primary Outcome Measure Information:
Title
Change in kidney function as measured by eGFR
Description
eGFR will be measured by blood test
Time Frame
Baseline, 6 months, 9 months, 12 months and 18 months
Title
Change in kidney function as measured by albuminuria
Description
Albuminuria will be measured by urine Albumin/Creatinine Ratio
Time Frame
Baseline, 6 months, 9 months, 12 months and 18 months
Title
Change in cardiac structure
Description
Cardiac structure as measured by the 3D echocardiogram
Time Frame
Baseline, month 9 and month15
Title
Change in blood insulin level
Description
Blood insulin level will be determined lab values
Time Frame
Baseline, month 6 and month 18
Title
Change in fasting blood sugar
Description
Fasting Blood sugar will be determined lab values
Time Frame
Baseline, month 6 and month 18
Title
Number of Urinary Tract infections
Description
Data to be gathered from chart review and patient report
Time Frame
up to 18 months
Title
Number of Genital infections
Description
Data to be gathered from chart review and patient report
Time Frame
up to 18 months
Secondary Outcome Measure Information:
Title
Change in kidney biopsy as measured by percentage of interstitial fibrosis
Time Frame
Baseline and 6 months
Title
Changes in Hemoglobin A1C as measured by blood work
Time Frame
Baseline, Months 3,6,9,12,15 and 18
Other Pre-specified Outcome Measures:
Title
Adverse events will be collected form the medical record and patient report
Time Frame
up to 18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Equal to or greater than 12 months and up tp 60 months post kidney transplant
Estimated glomerular filtration rate (eGFR) equal to or greater than 30ml/min/1.73m squared at screening
Standard immunosuppression, including calcineurin inhibitor, Mycophenolate Mofetil or Sodium and a glucocorticoid
Able to provide written consent -
Exclusion Criteria:
Type I diabetes
Any other solid organ transplant
Hemoglobin A1c greater than 12 %
SGLT2i use at the time of enrollment
Prior SGLT2i allergy or intolerance
Pregnant or nursing at the time of enrollment
History of antibody medicated rejection (AMR) or a Banff score greater than 2B for acute cellular rejection (ACR)
Active anticoagulant use other than aspirin 81 mg for primary prevention of cardiovascular disease
Known positive donor-specific antibodies prior to enrollment
Uncircumcised men
Greater than 2 urinary tract infections (UTI) over the 12 months prior to enrollment
Any genital infections over the 12 months prior to enrollment -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Research Coordinator
Phone
919-681-8730
Email
Teresa.conca@duke.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Daniel Edmonston, MD
Phone
919-668-4596
Email
daniel.edmonston@duke.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Myles Wolf, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Teresa Conca, BSN
Phone
919-681-8730
Email
Teresa.conca@duke.edu
First Name & Middle Initial & Last Name & Degree
Daniel Edmonston, MD
Phone
919-668-4956
Email
Daniel.edmonston@duke.edu
First Name & Middle Initial & Last Name & Degree
Myles Wolf, MD
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Individual data will not be shared
Citations:
PubMed Identifier
25081992
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.
Results Reference
result
PubMed Identifier
26981940
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.
Results Reference
result
PubMed Identifier
28605608
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.
Results Reference
result
PubMed Identifier
30415602
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.
Results Reference
result
PubMed Identifier
30862658
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.
Results Reference
result
PubMed Identifier
27470878
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.
Results Reference
result
Learn more about this trial
CardioRenal Effects of SGLT2 Inhibition in Kidney Transplant Recipients
We'll reach out to this number within 24 hrs