Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R01DK107680 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
Not provided
Not provided
Not provided
Research Design/Plan: After screening, each subject will receive 1 measurements of Endogenous Glucose Production [EGP] with prime-continuous Infusion of 3-3H-glucose. After completing the EGP measurement each subject will receive a Double Tracer Oral Glucose Tolerance Test [OGTT].
Methods: Visit 1: Screening. Medical history will be obtained, physical exam performed, and pregnancy test performed.
Visit 2: Endogenous Glucose Production Measurement: The rate of EGP will be measured with 3-3H-glucose.
Visit 3: Double Tracer OGTT
Eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning 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, subjects (20 per group) will receive one of the following medications: (i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg plus exenatide 5 ug. Following the test medication at 9 AM, blood samples will be drawn every 15 minutes for an additional 5 hours and plasma glucose, insulin, C-peptide, glucagon, cortisol, growth hormone, and catecholamine concentrations and glucose specific activity will be measured.
Visit 1: Screening. Medical history & physical exam will be performed. Blood will be drawn for fasting plasma glucose [FPG], routine blood chemistries, complete blood count [CBC], lipid profile, HbA1c, and thyroid function [TSH], Urinalysis, electrocardiogram [EKG], albumin/creatinine ratio and pregnancy test will be performed.
Visit 2: EGP Measurement: The rate of endogenous glucose production will be measured with 3-3H-glucose infusion. [3-3H]-glucose infusion will be started at 6 in the morning [AM] and continued until 2:30 afternoon [PM](5 hours after drug administration). At 6 AM a catheter will be placed into an anticubital vein and a prime (40 uCi x FPG/100)- continuous (0.4 uCi) infusion of [3-3H]- glucose will be started and continued until 2:30 PM. (5 hours after drug administration). Participant's hand will be placed in a box heated to 50-60°C (122-140°F). Baseline blood samples will be obtained at-210, -60, -50, -45, -40, -35, -30, -20, -10, and 0 . After 3.5 hours of tracer equilibration blood samples will be obtained every 10-20 minutes from 9 AM to 2 PM. Plasma glucose, insulin, C-peptide, glucagon, cortisol, growth hormone, and catecholamine concentrations, and [3-3H]-glucose specific activity will be measured. Urine will be collected from 6 to 9 AM and from 9 AM to 2 PM. Urinary volume and glucose concentration will be measured and urinary glucose excretion rate calculated. The study will end at 2:30 PM.
Visit 3: Double Tracer Oral Glucose Tolerance Test [OGTT]: Within the week after the measurement of EGP, all subjects will have a 5-hour OGTT with measurement of plasma glucose, insulin (I), C-peptide (CP), and glucagon concentrations at -180, -6-, -5-, -45, -40, -35, -30, -20, -10, 0 and every 15-30 minutes thereafter to obtain a measure of overall glucose tolerance, insulin secretion (CP0-120/G0-120), insulin sensitivity ([Matsuda Index=MI]), beta cell function, (CP0-120/G0-120 x MI), and suppression of plasma glucagon concentration (64). At 7 AM a catheter will be placed into an antecubital vein and a prime (25 uCi x FPG/100)- continuous (0.25 uCi) infusion of [3-3H]- glucose will be started and continued until 3 PM. Urinary volume and glucose concentration will be measured and urinary glucose excretion rate calculated.
HbA1c will be measured 2x, 1 on the day of the OGTT & 1 on the day of the EGP measurement.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. |
|
| Exenatide | Active Comparator | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. |
|
| Dapagliflozin | Active Comparator | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. |
|
| Exenatide and Dapagliflozin | Active Comparator | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo will be administered to 20 subjects after a 3 hour tracer equilibration period |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in EGP From Baseline to Post-oral Glucose Load. | The difference in rate of EGP during the last hour of the study (from 240-300 minutes) between drug-treatment and placebo treatment studies represents the effect of drug treatment on EGP, which will be compared among the 3 acute drug treatments (exenatide; dapagliflozin; exenatide plus dapagliflozin this data includes change in EGP above baseline following dapagliflozin alone vs dapagliflozin/exenatide) with ANOVA. | From baseline [-35 to 0min] to the last hour post-glucose load [240-300 minutes] |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Health System Texas Diabetic Institute | San Antonio | Texas | 78207 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35235659 | Derived | Alatrach M, Agyin C, Solis-Herrera C, Lavryneko O, Adams J, Gastaldelli A, Triplitt C, DeFronzo RA, Cersosimo E. Dapagliflozin Impairs the Suppression of Endogenous Glucose Production in Type 2 Diabetes Following Oral Glucose. Diabetes Care. 2022 Jun 2;45(6):1372-1380. doi: 10.2337/dc21-1798. |
Not provided
Not provided
All collected IPD, all IPD that underlie results in a publication
Data will be shared once study closes to enrollment and all data are analyzed and published. Informed consent documentation will be available for sharing.....
Access will be available through the journal website and on request through the PI.
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Type 2 Diabetes on Dapagliflozin | Patients will be randomized to receive dapagliflozin 10 mg daily, acutely and for 34 months. |
| FG001 | Type 2 Diabetes on Oral Placebo | Randomly selected group of patients with type 2 diabetes who will receive oral placebo for dapagliflozin at the same dosing schedule as dapagliflozin |
| FG002 | Type 2 Diabetes on Exenatide | patients ill be randomized to receive exenatide injections subcutaneously acutely and daily for 4 months. |
| FG003 | Type 2 Diabetes on Exenatide Plus Dapagliflozin | patients will be randomized to receive exenatide injections plus dapagliflozin acutely and for 4 months. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. Placebo: Placebo will be administered to 20 subjects after a 3 hour tracer equilibration period |
| BG001 |
| 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 EGP From Baseline to Post-oral Glucose Load. | The difference in rate of EGP during the last hour of the study (from 240-300 minutes) between drug-treatment and placebo treatment studies represents the effect of drug treatment on EGP, which will be compared among the 3 acute drug treatments (exenatide; dapagliflozin; exenatide plus dapagliflozin this data includes change in EGP above baseline following dapagliflozin alone vs dapagliflozin/exenatide) with ANOVA. | Type 2 diabetes | Posted | Mean | Standard Error | mg/kg.min | From baseline [-35 to 0min] to the last hour post-glucose load [240-300 minutes] |
|
4 months
Adverse events collected during clinical evaluation and laboratory analyses
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. Placebo: Placebo will be administered to 20 subjects after a 3 hour tracer equilibration period |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Genital Mycosis | Infections and infestations | Systematic Assessment | Fungal proliferation in the vaginal tract/urethra |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ralph A DeFronzo | UTexas_SanAntonio | 2105676691 | defronzo@uthscsa.edu |
Not provided
| 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 | Mar 21, 2019 | Apr 3, 2023 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077270 | Exenatide |
| C529054 | dapagliflozin |
| ID | Term |
|---|---|
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014688 | Venoms |
| D045424 | Complex Mixtures |
Not provided
Not provided
Participants will be randomized to one of four groups (20 per group): i) placebo; (ii) exenatide 5 ug subcutaneously; (iii) dapagliflozin (10 mg); and (iv) dapagliflozin 10 mg plus exenatide 5 ug
Not provided
Not provided
Not provided
Not provided
| Exenatide | Drug | Exenatide will be administered to 20 subjects after a 3 hour tracer equilibration period |
|
|
| Dapagliflozin | Drug | Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period |
|
|
| Exenatide and Dapagliflozin | Drug | Exenatide and Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period |
|
|
| Exenatide |
we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. Exenatide: Exenatide will be administered to 20 subjects after a 3 hour tracer equilibration period |
| BG002 | Dapagliflozin | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. Dapagliflozin: Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period |
| BG003 | Exenatide and Dapagliflozin | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. Exenatide and Dapagliflozin: Exenatide and Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ENDOGENOUS GLUCOSE PRODUCTION [EGP] | Mean | Standard Deviation | mg/kg.min |
|
| OG001 | Exenatide | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. Exenatide: Exenatide will be administered to 20 subjects after a 3 hour tracer equilibration period |
| OG002 | Dapagliflozin | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. Dapagliflozin: Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period |
| OG003 | Exenatide and Dapagliflozin | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. Exenatide and Dapagliflozin: Exenatide and Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period |
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 0 |
| 15 |
| EG001 | Exenatide | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. Exenatide: Exenatide will be administered to 20 subjects after a 3 hour tracer equilibration period | 0 | 25 | 0 | 25 | 4 | 25 |
| EG002 | Dapagliflozin | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. Dapagliflozin: Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period | 0 | 25 | 0 | 25 | 7 | 25 |
| EG003 | Exenatide and Dapagliflozin | we will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose conc compared to each agent alone. Exenatide and Dapagliflozin: Exenatide and Dapagliflozin will be administered to 20 subjects after a 3 hour tracer equilibration period | 0 | 25 | 0 | 25 | 6 | 25 |
|
| Nausea and Vomiting | Gastrointestinal disorders | Systematic Assessment | nausea and vomiting following subcutaneous administration of exenatide |
|
Not provided
Not provided
| D004700 | Endocrine System Diseases |
| D014118 |
| Toxins, Biological |
| D001685 | Biological Factors |