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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK107680 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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Purpose/Objectives: Examining the effect of SGLT2 inhibition on EGP and plasma glucose concentration in diabetic and non-diabetic subjects after kidney transplantation (i.e. renal denervation) or in subjects after renal sympathectomy (63) can add insight about the possible role of a neural arc which mediates the changes in plasma glucagon and/or insulin concentration in response to glucosuria.
Purpose/Objectives: Examining the effect of SGLT2 inhibition on EGP and plasma glucose concentration in diabetic and non-diabetic subjects after kidney transplantation (i.e. renal denervation) or in subjects after renal sympathectomy (63) can add insight about the possible role of a neural arc which mediates the changes in plasma glucagon and/or insulin concentration in response to glucosuria.
Research Design/Plan: After screening, eligible subjects will receive 2 measurements of endogenous glucose production with a prime-continuous infusion of 3-3H-glucose. Each measurement will be performed on a separate day in random order after a 10-12 hour overnight fast and will last 8 hours (from 6 AM to 2 PM). After a 3-hour tracer equilibration period, each subject will receive one of the following medications in random order: (i) placebo and (ii) dapagliflozin 10 mg. Following the test medication at 9 AM, blood samples will be drawn every 20 minutes for an additional 5 hours and plasma glucose, insulin, C-peptide, glucagon, catecholamine concentrations and tritiated glucose sp act will be measured.
Methods: Visit 1: Screening Visit 2: Endogenous Glucose Production Measurement (EGP) Visit 3: After completing the first EGP measurement, subjects will return to the Diabetes Research Unit for the second study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo first and then dapagliflozin | Experimental | Renal transplant subjects with intact native kidneys with Type 2 Diabetes Mellitus receive dapagliflozin then placebo |
|
| Dapagliflozin first then placebo | Active Comparator | Renal transplant subjects with intact native kidneys who are non-diabetic receive placebo then dapagliflozin |
|
| Control Group | Other | Subjects who are type 2 diabetes mellitus who have not undergone renal transplant. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dapagliflozin 10mg then Placebo Oral Tablet | Drug | SGLT2 inhibitor - Dapagliflozin then Placebo |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Endogenous Glucose Production (EGP) | Renal transplant subjects with native kidneys intact underwent measurement of EGP with an 8 hour infusion of 3-3H-glucose on 2 separate days with the administration in random order of either dapagliflozin 10mg or placebo after 3 hours of the tracer equilibration period. The equilibration at 3 hours was considered the baseline measurement. Measurement of change in endogenous glucose production was obtained for all subjects. | baseline and 240-300 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Fasting Plasma Glucose | Change in Fasting Plasma Glucose in Type 2 Diabetes Mellitus subjects only | baseline and 240-300 minutes |
| Change in Fasting Plasma Insulin | Change in Fasting Plasma Insulin in Type 2 Diabetes Mellitus subjects in diabetic subjects only |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ralph A DeFronzo, MD | The University of Texas Health Science at San Antonio | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78229 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32827269 | Derived | Daniele G, Solis-Herrera C, Dardano A, Mari A, Tura A, Giusti L, Kurumthodathu JJ, Campi B, Saba A, Bianchi AM, Tregnaghi C, Egidi MF, Abdul-Ghani M, DeFronzo R, Del Prato S. Increase in endogenous glucose production with SGLT2 inhibition is attenuated in individuals who underwent kidney transplantation and bilateral native nephrectomy. Diabetologia. 2020 Nov;63(11):2423-2433. doi: 10.1007/s00125-020-05254-w. Epub 2020 Aug 22. | |
| 32144165 | Derived |
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Diabetic and non-diabetic subjects were assigned to both interventions after randomization, either dapagliflozin first with placebo second, or placebo first and then dapagliflozin next.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dapagliflozin First - Diabetic | Subjects who have undergone renal transplant are randomly assigned to receive either dapagliflozin first followed by the placebo |
| FG001 | Placebo Oral Tablet First - Diabetic | Subjects who have undergone renal transplant are randomly assigned to receive placebo first followed by dapagliflozin |
| FG002 | Dapagliflozin First - Non-diabetic | Non-diabetic subjects who have undergone renal transplant are randomly assigned to dapagliflozin first and then receive placebo |
| FG003 | Placebo Oral Tablet First - Non-diabetic | Non-diabetic subjects who have undergone renal transplant are randomly assigned to placebo first and then receive dapagliflozin |
| FG004 | Control Group | Type 2 Diabetic subjects who did not undergo renal transplant and received dapagliflozin |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Subjects who underwent renal transplant surgery with intact native kidneys, and a type 2 diabetic control group that did not undergo renal transplant
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| ID | Title | Description |
|---|---|---|
| BG000 | Diabetic Subjects | Diabetic renal transplant subjects with native kidneys intact who were Type 2 diabetics |
| BG001 | Non-diabetic Subjects | Non-diabetic subjects after renal transplant with intact native kidneys |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Endogenous Glucose Production (EGP) | Renal transplant subjects with native kidneys intact underwent measurement of EGP with an 8 hour infusion of 3-3H-glucose on 2 separate days with the administration in random order of either dapagliflozin 10mg or placebo after 3 hours of the tracer equilibration period. The equilibration at 3 hours was considered the baseline measurement. Measurement of change in endogenous glucose production was obtained for all subjects. | The control group did not have renal surgery and were only administered the dapagliflozin, not the placebo, so no participants show for baseline or 240 to 300 minutes for placebo measurements, only for dapagliflozin. | Posted | Mean | Standard Deviation | mg/kg.min | baseline and 240-300 minutes |
|
Baseline to 8 hours
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Diabetic Subjects Dapagliflozin | Diabetic subjects who have undergone kidney surgery, and have a dapagliflozin infusion |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Carolina Solis-Herrera | University of Texas Health San Antonio | (210) 567-6691 | solisherrera@uthscsa.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 5, 2017 | Oct 10, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C529054 | dapagliflozin |
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Post renal transplant type 2 diabetes mellitus patients and non-diabetic mellitus patients after renal transplant with a control group of type 2 diabetes mellitus who have not undergone renal transplant
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| Placebo Oral Tablet then Dapagliflozin 10mg | Drug | Placebo then SGLT2 inhibitor - Dapagliflozin |
|
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| baseline and 240-300 minutes |
| Solis-Herrera C, Daniele G, Alatrach M, Agyin C, Triplitt C, Adams J, Patel R, Gastaldelli A, Honka H, Chen X, Abdul-Ghani M, Cersosimo E, Del Prato S, DeFronzo R. Increase in Endogenous Glucose Production With SGLT2 Inhibition Is Unchanged by Renal Denervation and Correlates Strongly With the Increase in Urinary Glucose Excretion. Diabetes Care. 2020 May;43(5):1065-1069. doi: 10.2337/dc19-2177. Epub 2020 Mar 6. |
| BG002 | Control Group | Type 2 diabetic subjects who did not under go renal transplant |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | 6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| A1C (average blood glucose level over 3 months) | Mean | Standard Deviation | Percentage of glycated hemoglobin |
|
| OG001 | Non-diabetic Subjects | Non-diabetic subjects after renal transplant with intact native kidneys |
| OG002 | Control Group | Type 2 diabetic subjects who did not undergo renal surgery and received dapagliflozin |
|
|
| Secondary | Change in Fasting Plasma Glucose | Change in Fasting Plasma Glucose in Type 2 Diabetes Mellitus subjects only | Only type 2 diabetic subjects were included in this group, so the 8 non-diabetic renal transplant subjects were not included. | Posted | Mean | Standard Deviation | mg/dL | baseline and 240-300 minutes |
|
|
|
| Secondary | Change in Fasting Plasma Insulin | Change in Fasting Plasma Insulin in Type 2 Diabetes Mellitus subjects in diabetic subjects only | Only type 2 diabetic subjects were included in this group, so the 8 subjects who were non-diabetic who had renal transplant were not included. | Posted | Mean | Standard Deviation | U/ml | baseline and 240-300 minutes |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | Diabetic Subjects Placebo | Diabetic subjects who have undergone kidney surgery, and have a placebo infusion | 0 | 6 | 0 | 6 | 0 | 6 |
| EG002 | Non-diabetic Subjects Dapagliflozin | Non-Diabetic subjects who have undergone kidney surgery, and have a dapagliflozin infusion | 0 | 8 | 0 | 8 | 0 | 8 |
| EG003 | Non-diabetic Subjects Placebo | Non-Diabetic subjects who have undergone kidney surgery, and have a placebo infusion | 0 | 8 | 0 | 8 | 0 | 8 |
| EG004 | Control Group | Type 2 Diabetic subjects who have not undergone renal surgery | 0 | 20 | 0 | 20 | 0 | 20 |
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| D004700 | Endocrine System Diseases |
| 240-300 minute measurement Placebo |
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| Baseline Measurement Dapagliflozin |
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| 240-300 minute measurement Dapagliflozin |
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| 240-300 minute measurement Placebo |
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| Baseline Measurement Dapagliflozin |
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| 240-300 minute measurement Dapagliflozin |
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