Glucagon-like Peptide-1's Effect on Renal Regional Blood Flow and the Renal Function in Patients With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Total blood flow
研究概览
简要总结
The goal of this double-blinded, placebo-controlled, randomized, crossover study is to examine the effect of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on renal hemodynamics and function in patients with type 2 diabetes mellitus (T2DM) and moderate chronic kidney disease (CKD).
The study will determine the effects of semaglutide on:
- Renal arterial blood flow, regional renal perfusion, and oxygenation
- Activity of the renin-angiotensin-aldosterone system (RAAS)
- The glomerular filtration rate (GFR)
- Sodium excretion in urine
- Blood pressure and heart rate
详细描述
Mechanistic studies conducted in healthy humans demonstrate a Glucagon-like peptide-1 (GLP-1)-mediated gut-kidney crosstalk. The expansion of extracellular fluid volume uncovers a natriuretic action of GLP-1. This feed-forward natriuretic system is associated with high renal extraction of GLP-1, suppression in circulating angiotensin II levels, and increased renal medullary and cortical perfusion and oxygenation. Besides potent glucose-lowering actions, Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve body weight, blood pressure, and dyslipidemia, and cardiovascular and renal outcome trials demonstrate beneficial actions of GLP-1RAs used in patients with type 2 diabetes mellitus (T2DM).
Thus the beneficial cardiovascular effects of GLP-1 may partly be related to renoprotection and might represent the restoration of the gut-kidney crosstalk.
The aim of the present study is to investigate possible mechanisms behind the renal effects of semaglutide in patients with type 2 diabetes mellitus and moderate chronic kidney disease.
This is a double-blinded, placebo-controlled, crossover study and patients will participate in two independent and randomized study periods with a washout period of around 4 weeks in between.
Fifteen male participants with type 2 diabetes mellitus in the age group 20-60 years are screened, randomized, and expected to complete the present study. Informed consent is obtained before the screening meeting followed by a 30-day run-in period prior to study days.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Type 2 diabetes mellitus diagnosed through either HbA1c ≥6,5% but ≤8,5%, or <6,5% combined with either fasting plasma glucose ≥7,0 mmol/L or plasma glucose ≥11,1 mmol/L two hours after an oral glucose tolerance test (OGTT).
- •Estimated glomerular filtration rate (eGFR, CKD-EPI) between 30-60 mL/min/1.73m2
- •Urine Albumin:Creatinine ratio (UACR) ≥30mg/g
- •Stable RAAS blockade (ACE inhibitors or angiotensin II receptor blocker (ARB) with stable dosis for 4 weeks prior to screening)
- •Discontinuation of treatment with selective sodium glucose transporter inhibitors (SGLT2i), dipeptidyl peptidase 4 inhibitors (DPP-4i), GLP-1R analogs, rapid-acting and mix insulin 30 days before screening.
排除标准
- •Immunosuppressive therapy within 30 days of screening
- •Alcohol abuse
- •Medical treatment with glucocorticoids
- •Kidney transplantation
- •Treatment for renal failure with dialysis
- •Myocardial infarction within 3 months of screening
- •Heart failure (NYHA 3-4)
- •Dysregulated arterial hypertension (systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥ 100 mm Hg)
- •Liver disease (ALAT >2 x normal value)
- •Conditions which may interfere with the glucose metabolism according to the PI
- •Severe claustrophobia
- •Elements incompatible with MRI
- •Abnormal kidney size and/or position
- •Venous and arterial anatomy hindering catheterization.
研究组 & 干预措施
Randomized to start with Semaglutide intervention in study period 1
Placebo will be given in study period 2
干预措施: Semaglutide, 0.5 mg/mL (Drug)
Randomized to start with Semaglutide intervention in study period 1
Placebo will be given in study period 2
干预措施: Placebo, Saline (Drug)
Randomized to start with Placebo intervention in study period 1
Semaglutide will be given in study period 2
干预措施: Semaglutide, 0.5 mg/mL (Drug)
Randomized to start with Placebo intervention in study period 1
Semaglutide will be given in study period 2
干预措施: Placebo, Saline (Drug)
结局指标
主要结局
Total blood flow
时间窗: Measured during 30 minutes of MRI. One measurement will be done on each study day, a total of 4 measurements for each participant, over the span of the study (approximately 1 year).
Volume of blood per unit time, ml/min
Regional renal perfusion
时间窗: Measured during 30 minutes of MRI. One measurement will be done on each study day, a total of 4 measurements for each participant, over the span of the study (approximately 1 year)
volume of blood per unit time per unit tissue mass, ml/min/g
次要结局
- Glomerular filtration rate(Measured with Tec99-DTPA clearance. One measurement will be done on each study day, a total of 4 measurements for each participant, over the span of the study (approximately 1 year))
- Activation of the renin angiotensin aldosterone system(Blood samples will be taken 3 times on each intervention day, a total of 6 measurements for each participant, over the span of the study (approximately 1 year))
- Heart Rate(Measured continuously during a 60 minute period on each intervention day, a total of 2 measurements for each participant, over the span of the study (approximately 1 year))
- Sodium excretion in urine(One measurement will be done on each intervention day, a total of 2 measurements for each participant, over the span of the study (approximately 1 year))
- Blood pressure(Measured continuously during a 60 minute period on each intervention day, a total of 2 measurements for each participant, over the span of the study (approximately 1 year))
研究者
Ali Asmar
Chief Physician, Associate Professor
Bispebjerg Hospital