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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK024092 | 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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The purpose of this study is to examine the effect of the chronic treatment of type 2 diabetes (T2DM) with dapagliflozin on: (1) mitochondrial gene function/expression and insulin signaling/action and (2) oral glucose tolerance and beta cell function. Dapagliflozin is a potent, highly specific inhibitor of renal glucose transport [SGLT2].
"Glucotoxicity" has been implicated as a cause of insulin resistance and impaired beta cell function in T2DM. Abundant support for the glucotoxicity hypothesis has been provided by in vivo and in vitro studies in animals, but a rigorous test of this hypothesis in man is lacking. The investigators propose to test the glucotoxicity hypothesis by chronically reducing the plasma glucose in type 2 diabetic subjects (T2DM) with an inhibitor of renal glucose transport, dapaglifozin, and examining the effect of restoration of normoglycemia on mitochondrial function and insulin signaling/sensitivity. Lastly, the investigators will test the "glucolipotoxicity" hypothesis, which states that the toxic effects of elevated plasma FFA on insulin sensitive tissues (i.e., muscle) are magnified in the presence of concurrent hyperglycemia. Thus, high glucose levels increase malonyl CoA, which inhibits CPT I, leading to accumulation of FACoA/DAG, which impair mitochondrial function and inhibit insulin action.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | this arm is control |
|
| Dapagliflozin | Experimental | Interventional arm |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dapagliflozin | Drug | Treatment arm, 10 mg per day for 2 weeks |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Insulin Sensitivity | The change in insulin sensitivity and total glucose disposal measured at two weeks with the insulin clamp compared to baseline. This is measured using TGD (whole body tissue glucose disposal)/SSPI (steady state plasma insulin concentration) ratio | baseline, two weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mitochondrial Function | The change in mitochondrial function/gene expression at two weeks compared to baseline. This was measured by energy expenditure. | baseline, two weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ralph DeFronzo, MD | The University of Texas Health Science Center at San Antonio | Principal Investigator |
| Devjit Tripathy, MD | The University of Texas Health Science Center at San Antonio | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Diabetes Division, UTHSCSA | San Antonio | Texas | 78229 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27561923 | Result | Daniele G, Xiong J, Solis-Herrera C, Merovci A, Eldor R, Tripathy D, DeFronzo RA, Norton L, Abdul-Ghani M. Dapagliflozin Enhances Fat Oxidation and Ketone Production in Patients With Type 2 Diabetes. Diabetes Care. 2016 Nov;39(11):2036-2041. doi: 10.2337/dc15-2688. Epub 2016 Aug 25. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | this arm is control Placebo: Patients are treated with placebo |
| FG001 | Dapagliflozin | Interventional arm Dapagliflozin: Treatment arm, 10 mg per day for 2 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | this arm is control Placebo: Patients are treated with placebo |
| BG001 | Dapagliflozin | Interventional arm Dapagliflozin: Treatment arm, 10 mg per day for 2 weeks |
| 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 Insulin Sensitivity | The change in insulin sensitivity and total glucose disposal measured at two weeks with the insulin clamp compared to baseline. This is measured using TGD (whole body tissue glucose disposal)/SSPI (steady state plasma insulin concentration) ratio | Posted | Mean | Standard Deviation | mg/kg.min per µU/ml | baseline, two weeks |
|
Adverse events are collected over a 2 week period
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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 | Placebo | this arm is control Placebo: Patients are treated with placebo | 0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Muhammad Abdul-Ghani | University of Texas Health San Antonio | 210-557-1157 | abdulghani@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 | Aug 10, 2016 | May 31, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| C565304 | Multiple Mitochondrial Dysfunctions Syndrome |
| D006029 | Glycosuria |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| 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 |
Patients are treated with placebo |
|
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| A1C (average blood glucose level over 3 months | Mean | Standard Deviation | percentage |
|
| Units | Counts |
|---|---|
| Participants |
|
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| Secondary | Change in Mitochondrial Function | The change in mitochondrial function/gene expression at two weeks compared to baseline. This was measured by energy expenditure. | Posted | Mean | Standard Deviation | cal/min.kg | baseline, two weeks |
|
|
|
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | Dapagliflozin | Interventional arm Dapagliflozin: Treatment arm, 10 mg per day for 2 weeks | 0 | 10 | 0 | 10 | 0 | 10 |
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| D014555 | Urination Disorders |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |