Effects of DPP-4 Inhibitor Therapy on Renal Sodium Handling and Renal Hemodynamics in Type 2 Diabetes Patients. The INDORSE Study: Inhibition of Dipeptidyl Peptidase IV: Outcomes on Renal Sodium Excretion
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Percent Change in Fractional Excretion of Sodium (FENA)
研究概览
简要总结
Background: Dedicated renal hemodynamic and renal function studies are lacking for DPP-4 inhibitors in patients with Type 2 diabetes; accordingly little is known regarding the mechanisms mediating the renal effects of DPP-4 inhibitors in humans.
Objectives: To evaluate the effect of DPP-4 inhibition acutely (single dose) and following short-term therapy (28 days) on renal sodium handling and renal hemodynamics and function in patients with type 2 diabetes and systolic hypertension.
Design: double-blind, randomized, placebo-controlled trial, Phase IV.
Patient population: 32 patients with Type 2 diabetes, HbA1c (6.5%-9%), with systolic blood pressure ranging from 120-160 mmHg.
Intervention: subjects will be randomized (1:1) to either sitagliptin (100 mg daily) or to placebo (1 tablet daily) for 28 days.
Endpoints: Fractional excretion of sodium, renal function, and renal hemodynamics.
详细描述
Background: DPP-4 inhibition improves glycemic control, modestly reduces blood pressure and may also reduce albuminuria in patients with Type 2 diabetes; effects which occur without significantly modifying heart rate or body weight. While preclinical studies have demonstrated that DPP-4 inhibition acutely increases urinary sodium excretion in addition to other favorable renal effects (anti-inflammatory, anti-proteinuric), few studies have examined the renal effects of DPP-4 inhibition either acutely or following short-term therapy in humans with type 2 diabetes. Considering the world-wide prevalence of Type 2 diabetes and the increasing use of DPP-4 inhibitors amongst patients, it is important to ascertain potential non-glycemic effects of DPP-4 inhibitors including those within the kidney.
Study Objectives: To determine effect(s) of DPP-4 inhibition on tubular sodium handling, renal hemodynamics, and renal function.
Study Design: double-blind, randomized, placebo-controlled trial, Phase IV.
Study Patients: 32 patients with Type 2 Diabetes and Systolic Hypertension (SBP 120-160 mmHg).
Endpoints: Fractional excretion of sodium, renal function (measured GFR), renal hemodynamics (effective renal plasma flow, filtration fraction, renal blood flow, renal vascular resistance), systemic hemodynamics (non-invasive cardiac monitoring), plasma neurohormones, urinary vasoactive mediators, markers of free radical stress.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Individuals of 18-70 years of age,
- •with Type 2 Diabetes,
- •with an HbA1c (6.5%-9%),
- •and with a systolic blood pressure (120-160 mmHg).
排除标准
- •Individuals with:
- •Type 1 Diabetes,
- •eGFR <50mL/min/1.73m,
- •pregnancy or breast feeding,
- •significant cardiac, pulmonary or liver disease,
- •prior history of pancreatitis, medullary thyroid cancer, multiple endocrine neoplasia syndromes,
- •SBP >161 mmHg, 7) DBP >100 mmHg,
- •alcohol or substance abuse,
- •states of secondary hypertension.
研究组 & 干预措施
Experimental arm
sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days
干预措施: Sitaglitpin (Drug)
Placebo arm
placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days
干预措施: Placebo (Other)
结局指标
主要结局
Percent Change in Fractional Excretion of Sodium (FENA)
时间窗: 3 Hrs post-administration after 1 month and after 1 dose
FENA at 3Hrs post-study drug administration after 1 month compared to FENA at 3Hrs post-study drug administration after 1 dose expressed as percent change, sitagliptin vs. placebo
次要结局
- Change in Glomerular Filtration Rate (GFR)(3 Hrs post-administration after 1 month and after 1 dose)
- Change in Fractional Excretion of Lithium (FELi)(3 Hrs post-administration after 1 month and after 1 dose)
- Change From Baseline in SDF-1alpha^1-67 (Intact) Measured by Immunoaffinity and Tandem Mass Spectrometry(3 Hr vs. baseline after 1 dose)
- Change From Baseline in SDF-1alpha^3-67 (Truncated) Measured by Tandem Mass Spectrometry With Antibody-based Affinity Enrichment(3Hrs vs baseline after 1 dose)
- Change in Systolic Blood Pressure (SBP), Non-invasive Cardiac Output Monitoring(3 Hrs post-administration after 1 month and after 1 dose)
- Change in Effective Renal Plasma Flow (ERPF)(3 Hrs post-administration after 1 month and after 1 dose)