A phase 4, monocenter, prospective, randomized, placebo-controlled, double-blind, cross-over, mechanistic intervention trial to assess effect of 4-week Ertugliflozin (SGLT-2 inhibitor) therapy on renal (cortical and medullary) oxygenation as determined by BOLD-MRI and renal (cortical and medullary) oxygen consumption as determined by positron emission tomography (PET) using ¹¹C-acetate in patients with type 2 diabetes mellitus and healthy controls.

A phase 4, monocenter, prospective, randomized, placebo-controlled, double-blind, cross-over, mechanistic intervention trial to assess effect of 4-week Ertugliflozin (SGLT-2 inhibitor) therapy on renal (cortical and medullary) oxygenation as determined by BOLD-MRI and renal (cortical and medullary) oxygen consumption as determined by positron emission tomography (PET) using ¹¹C-acetate in patients with type 2 diabetes mellitus and healthy controls. - Renal Oxygenation and Consumption, hemodynamic Kinetics, dIabetES

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON55355

Enrollment

Registered

2019-11-01

Start date

2019-10-01

Completion date

Unknown

Last updated

2024-04-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adult-onset diabetes Type 2 Diabetes Mellitus

Interventions

Cross-over conditions: (1) 4 weeks of ertugliflozin 15mg (2) 4 weeks of matchted placebo

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: Group 1:Participants with diabetes * Provision of signed and dated, written informed consent prior to any study specific procedures. * Caucasian*; female or male aged >=18 years and 31 U/L)*. * Type 2 diabetes mellitus since at least 3 years with HbA1c >= 6.5% (>=57mmol/ mol) and =25 kg/m² * In order to increase homogeneity. Group 2:age-matched and eGFR matched non-diabetic controls * Provision of signed and dated, written informed consent prior to any study specific procedures. * Caucasian*; female or male aged >=18 years and 31 U/L)*. * Normal glucose tolerance screening as confirmed by OGTT * Maximum tolerated antihypertensive dose of an ARB for at least 6 weeks prior to randomization. * eGFR 60-90 ml/min/1.73m² * BMI >=25 kg/m² * In order to increase homogeneity.

Exclusion criteria

Exclusion criteria: Group 1: participants with diabetes * 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 eGFR30mg/mmol) * Cardiovascular disease event in the last 6 months prior to enrollment, as assessed by the investigator: myocardial infarction, cardiac surgery or revascularization (CABG/PTCA), unstable angina, heart failure, transient ischemic attack (TIA) or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmnia. * Current/chronic use of the following medication: 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 and active nephritis * History of ketoacidosis * History of allergy/hypersensitivity to any of the testagents * Contra-indication for MRI * Any other condition that prevents participation as judged by the investigator Group 2: age-matched and eGFR matched non-diabetic controls * 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 eGFR30mg/mmol) * Cardiovascular disease event in the last 6 months prior to enrollment, as assessed by the investigator: myocardial infarction, cardiac surgery or revascularization (CABG/PTCA), unstable angina, heart failure, transient ischemic attack (TIA) or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmnia. * Current/chronic use of the following medication: oral glucocorticoids, 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 * History of allergy/hypersensitivity to any of the testagents. * Contra-indication for MRI * Any other condition that prevents participation as judged by the investigator

Design outcomes

Primary

Measure	Time frame
To investigate the effect of 4-week treatment with SGLT-2 inhibitor ertugliflozin 15mg QD on renal (separated as cortical and medullar) oxygenation measured by BOLD-MRI (R2*)	—

Secondary

Measure	Time frame
The most important secondary efficacy parameters include the effect of ertugliflozin on: • Renal oxygen consumption as determined by positron emission tomography (PET) ¹¹C-acetate (compartment model parameter k2). • Renal hemodynamic (GFR en ERPF); measured by the gold standard iohexol and PAH-clearance method • Calculated filtration fraction (FF) and local filtration fraction as measured by dynamic contrast enhanced MRI (DCE-MRI) • Renal efficiency measured as sodium reabsorption (TNa) divided by oxygen consumption • Cortical blood flow measured by contrast-enhanced ultrasound (CEUS) • Renal arterial blood flow measured by arterial spin labelling (ASL) and DCE-MRI • 24-hour sodium and glucose excretion after 2 days (acute response) and 4 weeks (chronic response) • Renal tubular function o Iohexol-corrected fractional sodium excretion o Urine osmolality o Urinary pH • Renal damage markers, measured as: o Urinary albumin excretion in 24-hour urine samples • Change in inflammatory profile assessed by flow cytometry and fluorescence activated cell sorting (FACS) • Changes in erythropoietin (EPO) levels • Changes in plasma substrates including glucose, free fatty acids, ketone bodies, and triglycerides • Insulin sensitivity (OGIS, Matsuda Index) and beta-cell function (as derived from HOMA-B) during an oral glucose tolerance test (OGTT). • Peripheral insulin extraction and total arterial insulin extraction (extraction x arterial flow) • Fasting energy expenditure by resting energy expenditure (REE)	—

Measure

Time frame

The most important secondary efficacy parameters include the effect of ertugliflozin on: • Renal oxygen consumption as determined by positron emission tomography (PET) ¹¹C-acetate (compartment model parameter k2). • Renal hemodynamic (GFR en ERPF); measured by the gold standard iohexol and PAH-clearance method • Calculated filtration fraction (FF) and local filtration fraction as measured by dynamic contrast enhanced MRI (DCE-MRI) • Renal efficiency measured as sodium reabsorption (TNa) divided by oxygen consumption • Cortical blood flow measured by contrast-enhanced ultrasound (CEUS) • Renal arterial blood flow measured by arterial spin labelling (ASL) and DCE-MRI • 24-hour sodium and glucose excretion after 2 days (acute response) and 4 weeks (chronic response) • Renal tubular function o Iohexol-corrected fractional sodium excretion o Urine osmolality o Urinary pH • Renal damage markers, measured as: o Urinary albumin excretion in 24-hour urine samples • Change in inflammatory profile assessed by flow cytometry and fluorescence activated cell sorting (FACS) • Changes in erythropoietin (EPO) levels • Changes in plasma substrates including glucose, free fatty acids, ketone bodies, and triglycerides • Insulin sensitivity (OGIS, Matsuda Index) and beta-cell function (as derived from HOMA-B) during an oral glucose tolerance test (OGTT). • Peripheral insulin extraction and total arterial insulin extraction (extraction x arterial flow) • Fasting energy expenditure by resting energy expenditure (REE)

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Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)