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| ID | Type | Description | Link |
|---|---|---|---|
| 5R01DK107680-02 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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In Protocol 2, the investigators will determine the role of pancreatic hormones (increase in plasma glucagon and decrease in plasma insulin concentration) in the stimulation of EGP following SGLT2 inhibition.
The inhibition of the renal (kidney) SGLT2 transporter has proven to be an effective therapeutic intervention to reduce plasma glucose levels (amount of glucose found in the liquid part of blood) and HbA1c.
In this study, the investigators hope to define the role of increased plasma glucagon, decline in plasma insulin, and fall in plasma glucose concentration. The investigators will examine whether the signal for the increase in EGP (endogenous glucose production) caused by glucosuria (an excess of sugar in the urine, typically associated with diabetes) is mediated via the decrease in plasma glucose and insulin concentrations, or by the increase in plasma glucagon concentration.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dapagliflozin | Active Comparator | 20 subjects will receive dapagliflozin 10mg |
|
| Placebo | Placebo Comparator | 10 subjects will receive placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dapagliflozin | Drug | SGLT2 inhibitor (dapagliflozin) |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Plasma Glucose Concentration | Change from baseline to the last hour of the study (240-300 minutes) in plasma glucose concentration | Baseline to 240-300 minutes |
| Change in Endogenous Glucose Production (EGP) | The change in endogenous glucose production is measured from baseline until the last hour of the study | Baseline to 240-300 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Plasma Insulin During Measurement of EGP | Measurement of change in plasma insulin concentration during measurement of of EGP from baseline to last hour of the study | Baseline to 240-300 minutes |
| Change in Glucagon During EGP Measurement |
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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 Center at San Antonio | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78229 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31915153 | Derived | Alatrach M, Laichuthai N, Martinez R, Agyin C, Ali AM, Al-Jobori H, Lavynenko O, Adams J, Triplitt C, DeFronzo R, Cersosimo E, Abdul-Ghani M. Evidence Against an Important Role of Plasma Insulin and Glucagon Concentrations in the Increase in EGP Caused by SGLT2 Inhibitors. Diabetes. 2020 Apr;69(4):681-688. doi: 10.2337/db19-0770. Epub 2020 Jan 8. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dapagliflozin | Subjects will receive dapagliflozin 10mg Dapagliflozin: SGLT2 inhibitor (dapagliflozin) |
| FG001 | Placebo | Subjects will receive placebo Placebo: Placebo Comparator |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study 1 |
| |||||||||||||
| Study 2: Glucose Clamp Conditions |
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| Study 3: Pancreatic Clamp Conditions |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dapagliflozin | Subjects will receive dapagliflozin 10mg Dapagliflozin: SGLT2 inhibitor (dapagliflozin) |
| BG001 | Placebo | Subjects will receive placebo Placebo: Placebo Comparator |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 Plasma Glucose Concentration | Change from baseline to the last hour of the study (240-300 minutes) in plasma glucose concentration | Posted | Mean | Standard Deviation | mg/dl | Baseline to 240-300 minutes |
|
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Adverse events were collected during the study procedure, from baseline to 300 minutes
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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 | Dapagliflozin | Subjects will receive dapagliflozin 10mg Dapagliflozin: SGLT2 inhibitor (dapagliflozin) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Systematic Assessment | Adverse event was experienced during study 3, the pancreatic clamp |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ralph DeFronzo | University of Texas Health San Antonio | 210-567-6691 | defronzo@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 | Sep 6, 2017 | Dec 2, 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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| Placebo | Drug | Placebo Comparator |
|
Measurement of change in glucagon during EGP measurement from baseline to the last hour of the study
| Baseline to 240-300 minutes |
| NOT COMPLETED |
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| NOT COMPLETED |
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| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
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| Diabetes Duration | Mean | Standard Deviation | years |
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| Free Plasma Glucose (FPG) | Mean | Standard Deviation | mg/dL |
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| HBA1c (3 month blood glucose level measure) | Mean | Standard Deviation | Percentage of glycated hemoglobin |
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| Glomerular Filtration Rate (eGFR) | Mean | Standard Deviation | ml/min |
|
| Participants |
|
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| Primary | Change in Endogenous Glucose Production (EGP) | The change in endogenous glucose production is measured from baseline until the last hour of the study | Posted | Mean | Standard Deviation | mg/kg.min | Baseline to 240-300 minutes |
|
|
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| Secondary | Change in Plasma Insulin During Measurement of EGP | Measurement of change in plasma insulin concentration during measurement of of EGP from baseline to last hour of the study | Posted | Mean | Standard Deviation | microUnits/mL | Baseline to 240-300 minutes |
|
|
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| Secondary | Change in Glucagon During EGP Measurement | Measurement of change in glucagon during EGP measurement from baseline to the last hour of the study | Posted | Mean | Standard Deviation | ng/ml | Baseline to 240-300 minutes |
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 4 |
| 20 |
| EG001 | Placebo | Subjects will receive placebo Placebo: Placebo Comparator | 0 | 10 | 0 | 10 | 0 | 10 |
|
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| D004700 | Endocrine System Diseases |
| Study 3 with pancreatic clamp |
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| Study 3 with pancreatic clamp |
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| Study 3 with pancreatic clamp |
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