SGLT2 INHIBITION AND STIMULATIION OF ENDOGENOUS GLUCOSE PRODUCTION Significance - PROTOCOL 3: Role of the Renal Nerves in the Increase in EGP in Response to Glucosuria
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Change in Endogenous Glucose Production (EGP)
研究概览
简要总结
Purpose/Objectives: Examining the effect of SGLT2 inhibition on EGP and plasma glucose concentration in diabetic and non-diabetic subjects after kidney transplantation (i.e. renal denervation) or in subjects after renal sympathectomy (63) can add insight about the possible role of a neural arc which mediates the changes in plasma glucagon and/or insulin concentration in response to glucosuria.
详细描述
Purpose/Objectives: Examining the effect of SGLT2 inhibition on EGP and plasma glucose concentration in diabetic and non-diabetic subjects after kidney transplantation (i.e. renal denervation) or in subjects after renal sympathectomy (63) can add insight about the possible role of a neural arc which mediates the changes in plasma glucagon and/or insulin concentration in response to glucosuria.
Research Design/Plan: After screening, eligible subjects will receive 2 measurements of endogenous glucose production with a prime-continuous infusion of 3-3H-glucose. Each measurement will be performed on a separate day in random order 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, each subject will receive one of the following medications in random order: (i) placebo and (ii) dapagliflozin 10 mg. Following the test medication at 9 AM, blood samples will be drawn every 20 minutes for an additional 5 hours and plasma glucose, insulin, C-peptide, glucagon, catecholamine concentrations and tritiated glucose sp act will be measured.
Methods: Visit 1: Screening Visit 2: Endogenous Glucose Production Measurement (EGP) Visit 3: After completing the first EGP measurement, subjects will return to the Diabetes Research Unit for the second study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age = 18-70 years
- •BMI = 18.5-40 kg/m2
- •HbA1c ≥ 7.0% and ≤10.0% for type 2 diabetics
- •males or females
- •Must be at least 3 months post renal transplantation and be on a stable dose of prednisone (≤5 mg/day), tacrolimus, and mycophenolate mofetil
- •Not taking any antidiabetic medications or who are treated with metformin, sulfonylurea, dipeptidyl peptidase 4 (DPP4) inhibitor, thiazolidinedione or some combination
- •Must be in good general health as determined by physical exam, medical history, blood chemistries, CBC, TSH, T4, EKG and urinanalysis
排除标准
- •Subjects who are taking insulin or SGLT2 inhibitor are excluded
- •Only subjects whose body weight has not been stable (± 3 lbs) over the preceding three months and/or who participate in an excessively heavy exercise program will be excluded.
- •Individuals with evidence of proliferative diabetic retinopathy, plasma creatinine >1.4 females or >1.5 males (and eGFR <45ml/min.1.73m2), or 24-hour urine albumin excretion > 300 mg will be excluded.
研究组 & 干预措施
Placebo first and then dapagliflozin
Renal transplant subjects with intact native kidneys with Type 2 Diabetes Mellitus receive dapagliflozin then placebo
干预措施: Dapagliflozin 10mg then Placebo Oral Tablet (Drug)
Placebo first and then dapagliflozin
Renal transplant subjects with intact native kidneys with Type 2 Diabetes Mellitus receive dapagliflozin then placebo
干预措施: Placebo Oral Tablet then Dapagliflozin 10mg (Drug)
Dapagliflozin first then placebo
Renal transplant subjects with intact native kidneys who are non-diabetic receive placebo then dapagliflozin
干预措施: Dapagliflozin 10mg then Placebo Oral Tablet (Drug)
Dapagliflozin first then placebo
Renal transplant subjects with intact native kidneys who are non-diabetic receive placebo then dapagliflozin
干预措施: Placebo Oral Tablet then Dapagliflozin 10mg (Drug)
Control Group
Subjects who are type 2 diabetes mellitus who have not undergone renal transplant.
干预措施: Dapagliflozin 10mg then Placebo Oral Tablet (Drug)
结局指标
主要结局
Change in Endogenous Glucose Production (EGP)
时间窗: baseline and 240-300 minutes
Renal transplant subjects with native kidneys intact underwent measurement of EGP with an 8 hour infusion of 3-3H-glucose on 2 separate days with the administration in random order of either dapagliflozin 10mg or placebo after 3 hours of the tracer equilibration period. The equilibration at 3 hours was considered the baseline measurement. Measurement of change in endogenous glucose production was obtained for all subjects.
次要结局
- Change in Fasting Plasma Glucose(baseline and 240-300 minutes)
- Change in Fasting Plasma Insulin(baseline and 240-300 minutes)