Acute Effects of Sodium-glucose Cotransporter-2 Inhibition on Renal Oxygenation and Autonomic Function in Type 1 Diabetes
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in Renal oxygenation
研究概览
简要总结
Background: Inhibiting the sodium-glucose cotransporter-2 (SGLT2) has been observed to reduce risk of cardiovascular events and kidney failure in type 2 diabetes. The exact mechanisms of the beneficial effects of SGLT2 inhibition (SGLT2i) are still unknown. Kidney hypoxia has been demonstrated in diabetic kidney disease and SGLT2i is thought to relieve hypoxia in the kidneys. Mitochondrial dysfunction and autonomic dysfunction might also contribute to kidney hypoxia.
Objective: The primary aim of the study is to assess the acute effects of SGLT2 inhibition on parameters reflecting oxygenation and oxygen consumption of the human kidney in persons with type 1 diabetes. Exploratory aims are to investigate acute changes in oxygen availability and oxygen access to the kidneys after SGLT2i. This include measures of peripheral blood oxygenation, mitochondrial function and autonomic function.
Methods: Acute intervention study with oral dapagliflozin given in two doses each of 50 mg or matching placebo as intervention. Kidney oxygenation and perfusion parameters will be assessed by blood-oxygen-dependant level magnetic resonance imaging. Mitochondrial function will be assessed by extracellular flux analysis on lymphocytes. Autonomic function will be assessed by measuring baroreflex sensitivity.
Design: Randomized, double blinded, placebo-controlled, cross-over intervention study.
Study population: Fifteen healthy controls are recruited by advertisement and 15 patients with type 1 diabetes recruited from Steno Diabetes Center Copenhagen.
Endpoints: Primary end-point: Renal cortical and medullary oxygenation (T2*). Exploratory end-points: Renal cortical and medullary perfusion, renal artery flow, renal oxygen consumption, peripheral capillary oxygen saturation (SpO2), arterial oxygen partial pressure (PaO2), arterial oxygen saturation (SaO2), lymphocyte mitochondrial function, baroreflex sensitivity.
Timeframe: Inclusion of patients from January 2020. Last patient last visit January 2021. Data analysis completed spring 2021, presentation autumn 2021 and publications Winter 2021.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Group allocation is concealed to patients as well as investigators. 60 sequentially numbered, opaque, sealed envelopes will be produced by Glostrup Apotek. All persons involved in the conduct of the study are blinded to the randomization code. Randomization codes and envelopes are stored securely at the study site available only for the unblinded site staff in charge of randomizing subjects and dispensing study products to subjects. Sealed codes are marked according to randomization code and distributed according to a pre-distributed order. Should unblinding of a study participant be necessary because of an emergency, a dedicated person at Steno Diabetes Center Copenhagen, not involved in the study, will perform the procedure. Alternatively, the Principal investigator will be able to perform unblinding
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Dapagliflozin
Patients in the active arm will be treated with dapagliflozin 50 mg once on site for visit 2 and once at home on the evening before visit 3.
Forxiga®, dapagliflozin 10 mg film-coated tablet.
For further information please refer to:
https://www.ema.europa.eu/en/documents/product-information/forxiga-epar-product-information_en.pdf.
干预措施: Forxiga (Drug)
Placebo
Patients in the placebo arm will be treated with placebo once on site for visit 2 and once at home on the evening before visit 3.
Placebo drug:
The composition equals the composition of Forxiga® - just with the active ingredient omitted. Active drug and placebo are similar in appearance and smell.
干预措施: Forxiga (Drug)
结局指标
主要结局
Change in Renal oxygenation
时间窗: From baseline to +6 hours from intervention
BOLD MRI assessing the transverse relaxation time of atomic nuclei in the tissue (T2\*) in miliseconds (ms).
次要结局
- Change in levels of circulating inflammatory markers(From baseline to +12 hours from intervention)
- Change in renal oxygen consumption(From baseline to +6 hours from intervention)
- Change in renal cortical and medullary perfusion(From baseline to +6 hours from intervention)
- Change in renal artery flow(From baseline to +6 hours from intervention)
- Change in Peripheral Blood Monocyte mitochondrial function(From baseline to +12 hours from intervention)
- Change in baroreflex sensitivity(From baseline to +12 hours from intervention)
- Change in blood oxygen partial pressure (PaO2)(From baseline to +6 hours from intervention)
- Change in arterial blood oxygen saturation(From baseline to +6 hours from intervention)
- Change in peripheral capillary oxygen saturation (SpO2)(From baseline to +6 hours from intervention)