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| ID | Type | Description | Link |
|---|---|---|---|
| 2R01DK097554-06 | 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 aim of this study is to examine the role of autonomic nervous system in the increase in hepatic glucose production in response to glucosuria caused by inhibition of renal glucose uptake
Purpose/Objectives: To investigate the effect of empagliflozin, an SGLT2 inhibitor on hepatic glucose production and the role of autonomic nervous system in mediating the increase in hepatic glucose production in response glucosuria Research Design/Plan: the role of autonomic nervous system in the increase in hepatic glucose production caused by empagliflozin will be examined with norepinephrine (NE) turnover in two protocols. The first protocol is cross sectional, in which 36 T2DM patients will receive hepatic glucose production (HGP) and NE turnover will be measured before and after empagliflozin or placebo administration. In protocol 2, diabetic and non-diabetic subjects will receive baseline HGP, NE turnover, hepatic glucose uptake (HGU) and liver fat measurement before at 2 days after the start and 12 weeks after empagliflozin or placebo treatment.
Methods: the following techniques will be employed (1) Measurement of hepatic glucose production with 3H-glucose infusion, with and without glucose clamp, (2) substrate oxidation with indirect calorimetry and plasma ketone/lactate/insulin/glucagon concentrations; (3) Measurement of HGU with Oral-IV double tracer infusion; (4) Measurement of whole body norepinephrine turnover with 3H-norepinephrine infusion; (5) Measurement of heart rate variability; (6) Measurement of liver fat content with 1H-MRS Clinical Relevance: The results of the present studies will help identify the mechanism responsible for the increase in HGP caused by empagliflozin and the increase in ketone production. The first action of the drug ameliorates its clinical efficacy while the second increases the risk of adverse events (ketoacidosis). Identifying the mechanisms underlying these actions will help developing therapeutic strategies which increase the drug clinical efficacy and mitigates its adverse events.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental | empagliflozin 25 mg per day |
|
| control | Placebo Comparator | matching placebo 1 pill per day |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Empagliflozin 25 MG | Drug | subjects will receive daily dose of 25mg of empagliflozin for 3 months |
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| Measure | Description | Time Frame |
|---|---|---|
| Effect of Empagliflozin on Autonomic Nervous System | autonomic activity will be measured with as NE turnover rate. Total-body NE turnover rate was measured with 3H-NE infusion. A prime (3.8 µCi)-continuous (0.38 µCi/min) infusion of 3H-NE was started and continued for 60 minutes. Arterialized blood samples were collected before the start and between the 40-60 minute time period after the start of 3H-NE infusion. Total body NE turnover rate was calculated as the 3H-NE infusion rate (dpm/min) divided by the steady state plasma 3H-NE specific activity (dpm/pg) after 30 minutes | Baseline and 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Hepatic Glucose Production | HGP will be measured with tracer dilution technique | Baseline and 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Percentage Change From Baseline to 12 Weeks in Hepatic Fat Content | the effect of treatment on hepatic fat content will be measured with MRS. | Baseline and12 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Muhammad Abdul-Ghani, MD, PhD | Diabetes Division, UTHSCSA | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Diabetes Division, UTHSCSA | San Antonio | Texas | 78229 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment | empagliflozin 25 mg per day Empagliflozin 25 MG: subjects will receive daily dose of 25mg of empagliflozin for 3 months |
| FG001 | Control | matching placebo 1 pill per day Control: Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment | empagliflozin 25 mg per day Empagliflozin 25 MG: subjects will receive daily dose of 25mg of empagliflozin for 3 months |
| BG001 | Control | matching placebo 1 pill per day Control: Placebo |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | 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 | Effect of Empagliflozin on Autonomic Nervous System | autonomic activity will be measured with as NE turnover rate. Total-body NE turnover rate was measured with 3H-NE infusion. A prime (3.8 µCi)-continuous (0.38 µCi/min) infusion of 3H-NE was started and continued for 60 minutes. Arterialized blood samples were collected before the start and between the 40-60 minute time period after the start of 3H-NE infusion. Total body NE turnover rate was calculated as the 3H-NE infusion rate (dpm/min) divided by the steady state plasma 3H-NE specific activity (dpm/pg) after 30 minutes | Posted | Mean | Standard Error | ng/min | Baseline and 12 weeks |
|
12 weeks
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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 | Treatment | empagliflozin 25 mg per day Empagliflozin 25 MG: subjects will receive daily dose of 25mg of empagliflozin for 3 months |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vaginal yeast infection | Reproductive system and breast disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Muhammad Abdul-Ghani | UTHSCSA | 210 567 6691 | 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 | May 23, 2020 | Feb 26, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| C570240 | empagliflozin |
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subjects will receive in parallel a treatment with empagliflozin or placebo for 3 months hepatic glucose metabolism and norepinephrine turnover will be studied before and after treatment
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the study is placebo controlled double blinded. randomization will be made by pharmacist and the randomization code will be kept in the pharmacy
| Control | Drug | Placebo |
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| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants | No |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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matching placebo 1 pill per day Control: Placebo |
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| Secondary | Hepatic Glucose Production | HGP will be measured with tracer dilution technique | one patient in treatment arm did not complete the study due to Covid-19. | Posted | Mean | Standard Error | mg/kg/min | Baseline and 12 weeks |
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| Other Pre-specified | Absolute Percentage Change From Baseline to 12 Weeks in Hepatic Fat Content | the effect of treatment on hepatic fat content will be measured with MRS. | Thirty individuals with T2D and 27 without were randomly assigned to receive in double-blind fashion empagliflozin or matching placebo (2:1 ratio) for 12 weeks. | Posted | Mean | Standard Error | percentage of liver fat content | Baseline and12 weeks |
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| 0 |
| 36 |
| 0 |
| 36 |
| 2 |
| 36 |
| EG001 | Control | matching placebo 1 pill per day Control: Placebo | 0 | 36 | 0 | 36 | 1 | 36 |
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