Renal Oxygenation, Oxygen Consumption and Hemodynamic Kinetics in Type 2 DIabetes: an Ertugliflozin Study.

• Status: Recruiting
• Trial end date: 2022-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Current study will render insight in to the role of renal hypoxia in the diabetic kidney and is able to associate its finding with measurements of renal perfusion and glomerular filtration rate. Moreover, this research will focus on the effects of sodium-glucose cotransporter 2 inhibition on renal tissue oxygenation and oxygen consumption as well as a change in intrarenal hemodynamics and perfusion, and a shift of fuel metabolites. Elucidation the mechanisms underlying the effects of SGLT2 inhibition will advance our knowledge and contribute to their optimal clinical utilization in the treatment of chronic kidney disease in diabetes and possibly beyond.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: VU University Medical Center
• Treatments: 5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-1-hydroxymethyl-6,8-dioxabicyclo(3.2.1)octane-2,3,4-triol; Ertugliflozin

Criteria

Group 1: T2DM patients

Inclusion criteria

• Provision of signed and dated, written informed consent prior to any study specific procedures.

• Caucasian*; female or male aged ≥18 years and <80 years. Females must be post-menopausal (defined as no menses >1 year and follicle stimulating hormone (FSH) >31 U/L)*.

• Type 2 diabetes mellitus since at least 3 years with HbA1c ≥ 6.5% (≥57mmol/mol) and <10% (<94mmol/mol)

• An appropriate stable dose of metformin and/or sulfonylurea as glucose-lowering therapy for the last 12 weeks

• Maximum tolerated antihypertensive dose of an ARB for at least 6 weeks prior to randomization.

• eGFR 60-90 ml/min/1.73m²

• BMI 25-35 kg/m² * In order to increase homogeneity

Exclusion criteria

• Involvement in the planning and/or conduction of another study

• Participation in another clinical study with an investigational product during the last 3 months

• Diagnosis of type 1 diabetes mellitus

• CKD defined as eGFR<60 ml/min/1.73m² or albuminuria (defined as an UACR > 2.5 mg/mol).

• Cardiovascular disease event in the last 6 months prior to enrollment as assessed by the investigator, including: myocardial infarction, cardiac surgery or revascularization (CABG/PTCA), unstable angina, heart failure, transient ischemic attack (TIA) or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia.

• Current/chronic use of the following medication: insulin, thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors, oral glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs), diuretics, and monoamine oxidase inhibitors.

• Current urinary tract infection or active nephritis

• History of ketoacidosis

• History of allergy/hypersensitivity to any of the test agents.

Group 2: Age-matched and eGFR-matched non-diabetic controls Inclusion criteria

• Provision of signed and dated, written informed consent prior to any study specific procedures.

• Caucasian*; female or male aged ≥18 years and <80 years. Females must be post-menopausal (defined as no menses >1 year and follicle stimulating hormone (FSH) >31 U/L)*.

• Normal glucose tolerance at screening as confirmed by OGTT

• Maximum tolerated antihypertensive dose of an ARB for at least 6 weeks prior to randomization in case of hypertension.

• BMI 25-35 kg/m2

• eGFR 60-90ml/min * In order to increase homogeneity

Exclusion criteria

• Involvement in the planning and/or conduction of another study

• Participation in another clinical study with an investigational product during the last 3 months

• CKD defined as eGFR<60ml/min or macro-albuminuria or proteinuria

• Cardiovascular disease event in the last 6 months prior to enrollment, as assessed by the investigator, including: myocardial infarction, cardiac surgery or revascularization (CABG/PTCA), unstable angina, heart failure, transient ischemic attack (TIA) or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia.

• Use of medication that may interfere with study endpoints non-steroidal anti-inflammatory drugs (NSAIDs), immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs), diuretics, and monoamine oxidase inhibitors.

• Current urinary tract infection and active nephritis

• Any other condition that prevents participation as judged by investigator.