SGLT-2i, Heart, Improvement of Cardiovascular Autonomic Neuropathy
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Endpoint related to Objective #1: to verify the effect of SGLT-2is on HRV as shown by the difference in LF:HF ratio (a frequency domain measured as improvement of 20% in LF:HF ratio from baseline to end of treatment (6 months).
研究概览
简要总结
Primary Objective #1: to evaluate whether the cardiovascular effects of SGLT-2is are, at least in part, mediated by autonomic innervation in patients with type 2 diabetes mellitus; Primary Objective #2: to explore the effects of SGLT2is on the progression of CAN in patients affected by type 2 diabetes mellitus;
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Informed consent obtained before any study-specific procedures. Patients must be able to understand and be willing to sign a written informed consent
- •Patients who are intolerant to metformin, or in metformin failure, or present clinical indications for initiating SGLT2 inhibitor therapy (e.g., heart failure, diabetic kidney disease), in accordance with current clinical guidelines
- •Men and women with type 2 diabetes mellitus
- •age > 45 years old
- •patients with stable medical therapy including other anti-hyperglycemic agents alone or in combination with a basal insulin analogue for at least 3 months prior to the screening visit (including stable insulin dose defined as no variation over 30% in daily insulin dose in the preceding 3 months, as evaluated by the Investigator)
- •HbA1c above or equal to 7.0% but less than 8.5% at screening
- •Women of childbearing potential must have a negative blood or urine pregnancy test at the baseline visit
- •Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 5.9 of the protocol
- •Ability to take oral medications
- •Will and ability to comply with the protocol
排除标准
- •Type 1 diabetes mellitus
- •chronic obstructive lung disease with evidence of bronchospasm (e.g. asthma)
- •long QT syndrome
- •severe hypotension
- •decompensated heart failure
- •History of diabetic ketoacidosis (DKA), unless a clear and modifiable precipitating factor (e.g., ketogenic diet, excessive alcohol consumption) has been identified and eliminated
- •Female during pregnancy and breastfeeding
- •Certified or suspected hypersensitivity to SGLT2 inhibitors
- •Patients on dialysis or with estimated glomerular filtration rate (eGFR) below the following thresholds, depending on the assigned treatment: - eGFR <45 mL/min/1.73 m² for patients planned to receive ertugliflozin - eGFR <30 mL/min/1.73 m² for patients planned to receive empagliflozin, canagliflozin, or dapagliflozin;
- •diagnosis of chronic obstructive pulmonary disease or respiratory failure
- •inability to provide informed consent
- •patients with history of breast, bladder and prostate cancer
- •previous diagnosis of Latent Autoimmune Diabetes of Adults (LADA)
- •use of SGLT-2is in the 90 days prior to screening, acute decompensation of glycemic control requiring immediate intensification of treatment to prevent acute complications (e.g. diabetic ketoacidosis) in 90 days prior to screening
- •acute coronary or cerebro-vascular event in the 90 days prior to randomization, currently planned coronary, carotid or peripheral artery revascularization, NYHA class III or IV, unstable angina
- •sick sinus syndrome, second or third degree atrio-ventricular block (except in patients with a functioning artificial pacemaker)
结局指标
主要结局
Endpoint related to Objective #1: to verify the effect of SGLT-2is on HRV as shown by the difference in LF:HF ratio (a frequency domain measured as improvement of 20% in LF:HF ratio from baseline to end of treatment (6 months).
Endpoint related to Objective #1: to verify the effect of SGLT-2is on HRV as shown by the difference in LF:HF ratio (a frequency domain measured as improvement of 20% in LF:HF ratio from baseline to end of treatment (6 months).
Endpoint related to Objective #2: to verify the effect of SGLT-2 on CAN progression as shown by the improvement in at least one of the three CART parameter AND an improvement in glucose variability from baseline to end of treatment (6 months)
Endpoint related to Objective #2: to verify the effect of SGLT-2 on CAN progression as shown by the improvement in at least one of the three CART parameter AND an improvement in glucose variability from baseline to end of treatment (6 months)
次要结局
- to assess the results of SGLT2i treatment on pancreatic beta cell function (i.e., glucose sensitivity and insulin secretion parameters including those derived from the Mixed Meal Test (MMT)) in patients with and without CAN after 6 months intervention with SGLT2i.
- to assess the difference in glycemic variability expressed as mean amplitude of glycemic excursions (MAGE) measured for 2 weeks flash glucose monitoring at baseline and after 6 months of treatment with SGLT-2i.
- to explore difference in CAN progression expressed as changes in cardiovascular autonomic reflex tests (CARTs) as defined by: a) expiration/inspiration (E/I) ratio, b) 30:15 ratio and c) Valsalva ratio.
研究者
Andrea Giaccari
Scientific
Universita Cattolica Del Sacro Cuore