Type II; Diabetes Clinical Trial
— AZ11040Official title:
Paradoxical Stimulation of Hepatic Glucose Production With Dapagliflozin (P2)
Verified date | November 2019 |
Source | The University of Texas Health Science Center at San Antonio |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
To determine the role of plasma glucagon and insulin in the rise of endogenous glucose production (EGP) following the SGLT2 inhibition.
Status | Completed |
Enrollment | 30 |
Est. completion date | November 16, 2019 |
Est. primary completion date | November 16, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility |
Inclusion Criteria: - T2DM according to ADA criteria-HbA1C < 8.0% - BMI = 25-35 kg/m2 - Subjects must be in good general health as determined by physical exam, medical history, blood chemistries, CBC, TSH, T4, EKG and urinanalysis - Body weight has been stable (± 3 lbs) over the preceding three months - Do not participate in an excessively heavy exercise program - Taking stable dose (more than 3 months) of monotherapy or combination therapy with metformin and/or a sulfonylurea Exclusion Criteria: - Subjects taking drugs known to affect glucose metabolism (other than metformin and sulfonylurea) will be excluded - Individuals with evidence of proliferative diabetic retinopathy, plasma creatinine >1.4 females or >1.5 males, or 24-hour urine albumin excretion > 300 mg will be excluded |
Country | Name | City | State |
---|---|---|---|
United States | University of Texas Health Science Center | San Antonio | Texas |
Lead Sponsor | Collaborator |
---|---|
The University of Texas Health Science Center at San Antonio |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
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 | |
Primary | 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 | |
Primary | 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 | |
Primary | 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 | |
Primary | 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 | |
Primary | 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 | |
Secondary | 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 | |
Secondary | 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 | |
Secondary | Change in Glucagon: Study 1 | Change in glucagon concentrations during measurement of EGP | Baseline to 240-300 minutes | |
Secondary | 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 | |
Secondary | 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 |
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