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Clinical Trial Details

Trial ID: L3811
Source ID: NCT02984644
Associated Drug: Dapagliflozin
Title: Paradoxical Stimulation of Hepatic Glucose Production With Dapagliflozin
Acronym: AZ11040
Status: COMPLETED
Study Results: YES
Results: https://ClinicalTrials.gov/show/NCT02984644/results
Conditions: Type II; Diabetes
Interventions: DRUG: Dapagliflozin|DRUG: Placebo
Outcome Measures: Primary: Measurement of the Change in Plasma Glucose (mg/dL): Study 1, Change from baseline to the last hour of the study (240-300 minutes) in plasma glucose concentration, Baseline to 240-300 minutes|Change in Plasma Glucose Measurement Using a Glucose Clamp: Study 2, Change from baseline to the last hour of the study (240-300 minutes) in plasma glucose for study 2: EGP plus glucose clamp. The glucose clamp technique is achieved by increase plasma glucose concentration to 125 mg/dl above basal levels by a continuous infusion of glucose. This hyperglycemic plateau is maintained by adjustment of a variable glucose infusion, based on the rate of insulin secretion and glucose metabolism. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of insulin secretion and glucose metabolism. The 3-3H-glucose infusion will be started at 6 AM to measure the basal rate of EGP. After a 3 hour tracer equilibration period (at 9 AM) subjects will receive dapagliflozin (10 mg) or placebo, and the plasma glucose conc will be measured every 5 minutes for 5 hours (from 9AM to 2 PM), Baseline to 240-300 minutes|Change in Plasma Glucose Using a Pancreatic Clamp: Study 3, Change from Baseline to the last hour of the study (240-300 minutes) in plasma glucose using a pancreatic clamp. In this study, EGP will be measured as described in Study 1 and plasma insulin and glucagon concentrations will be clamped at the basal level using the pancreatic clamp technique. Plasma glucose concentration will be allowed to decrease spontaneously after dapagliflozin or placebo administration. Somastatin will be infused with glucagon and insulin to replace basal plasma glucagon and insulin until study end., Baseline to 240-300 minutes|Change in EGP: Study 1, Change from baseline to the last hour of the study (240-300 minutes) in EGP, Baseline to 240-300 minutes|Change in EGP With Glucose Clamp: Study 2, Change from baseline to the last hour of the study (240-300 minutes) in EGP using a glucose clamp. The glucose clamp technique is achieved by increase plasma glucose concentration to 125 mg/dl above basal levels by a continuous infusion of glucose. This hyperglycemic plateau is maintained by adjustment of a variable glucose infusion, based on the rate of insulin secretion and glucose metabolism. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of insulin secretion and glucose metabolism. The 3-3H-glucose infusion will be started at 6 AM to measure the basal rate of EGP. After a 3 hour tracer equilibration period (at 9 AM) subjects will receive dapagliflozin (10 mg) or placebo, and the plasma glucose conc will be measured every 5 minutes for 5 hours (from 9AM to 2 PM), Baseline to 240-300 minutes|Change in EGP With Pancreatic Clamp: Study 3, Change from baseline to the last hour of the study (240-300 minutes) of EGP with a pancreatic clamp. In this study, EGP will be measured as described in Study 1 and plasma insulin and glucagon concentrations will be clamped at the basal level using the pancreatic clamp technique. Plasma glucose concentration will be allowed to decrease spontaneously after dapagliflozin or placebo administration. Somastatin will be infused with glucagon and insulin to replace basal plasma glucagon and insulin until study end.VIn this study, EGP will be measured as described in Study 1 and plasma insulin and glucagon concentrations will be clamped at the basal level using the pancreatic clamp technique. Plasma glucose concentration will be allowed to decrease spontaneously after dapagliflozin or placebo administration. Somastatin will be infused with glucagon and insulin to replace basal plasma glucagon and insulin until study end., Baseline to 240-300 minutes | Secondary: Change in Plasma Insulin Concentrations: Study 1, Plasma insulin concentrations during measurement of EGP, Baseline to 240-300 minutes|Plasma Insulin Concentrations During Measurement of EGP Plus Glucose Clamp: Study 2, Plasma insulin concentration is measured from baseline to the last hour of the study while using a glucose clamp. The glucose clamp technique is achieved by increase plasma glucose concentration to 125 mg/dl above basal levels by a continuous infusion of glucose. This hyperglycemic plateau is maintained by adjustment of a variable glucose infusion, based on the rate of insulin secretion and glucose metabolism. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of insulin secretion and glucose metabolism. The 3-3H-glucose infusion will be started at 6 AM to measure the basal rate of EGP. After a 3 hour tracer equilibration period (at 9 AM) subjects will receive dapagliflozin (10 mg) or placebo, and the plasma glucose conc will be measured every 5 minutes for 5 hours (from 9AM to 2 PM), Baseline to 240-300 minutes|Change in Plasma Insulin While Using Pancreatic Clamp: Study 3, Plasma insulin concentration during measurement of EGP while using pancreatic clamp. In this study, EGP will be measured as described in Study 1 and plasma insulin and glucagon concentrations will be clamped at the basal level using the pancreatic clamp technique. Plasma glucose concentration will be allowed to decrease spontaneously after dapagliflozin or placebo administration. Somastatin will be infused with glucagon and insulin to replace basal plasma glucagon and insulin until study end., Baseline to last hour of the study|Change in Glucagon: Study 1, Change in glucagon concentrations during measurement of EGP, Baseline to 240-300 minutes|Change in Glucagon Using Glucose Clamp: Study 2, Plasma glucagon concentration during measurement of EGP using a glucose clamp. The glucose clamp technique is achieved by increase plasma glucose concentration to 125 mg/dl above basal levels by a continuous infusion of glucose. This hyperglycemic plateau is maintained by adjustment of a variable glucose infusion, based on the rate of insulin secretion and glucose metabolism. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of insulin secretion and glucose metabolism., Baseline to 240-300 minutes|Change in Glucagon Using Pancreatic Clamp: Study 3, Measurement of change in plasma glucagon from baseline to one hour prior to end of study while using a pancreatic clamp. In this study, EGP will be measured as described in Study 1 and plasma insulin and glucagon concentrations will be clamped at the basal level using the pancreatic clamp technique. Plasma glucose concentration will be allowed to decrease spontaneously after dapagliflozin or placebo administration. Somastatin will be infused with glucagon and insulin to replace basal plasma glucagon and insulin until study end., Baseline to 240-300 minutes
Sponsor/Collaborators: Sponsor: The University of Texas Health Science Center at San Antonio
Gender: ALL
Age: ADULT, OLDER_ADULT
Phases: PHASE3
Enrollment: 30
Study Type: INTERVENTIONAL
Study Designs: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (PARTICIPANT)|Primary Purpose: TREATMENT
Start Date: 2017-09-06
Completion Date: 2019-11-16
Results First Posted: 2019-12-18
Last Update Posted: 2019-12-18
Locations: University of Texas Health Science Center, San Antonio, Texas, 78229, United States
URL: https://clinicaltrials.gov/show/NCT02984644