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

NCT04027530 | Completed Phase 4

• 1 other identifier: DC2019 ROCKIES 1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 2 Diabetes Mellitus; Diabetic Kidney Disease; Diabetic Nephropathy; Renal Hypoxia; Renoprotection; SGLT2 Inhibitor; Ertugliflozin

Outcome Measures

Primary Outcomes (1)

• Renal oxygenation measured by BOLD-MRI (R2*)

  Renal (separated as cortical and medullar) oxygenation measured by BOLD-MRI (R2\*)

  After 4 week treatment with ertugliflozin 15mg QD versus placebo

Secondary Outcomes (21)

• Renal oxygen consumption by PET/CT-scan using 11C-Acetate

  After 4 week treatment with active drug intervention versus placebo

• Renal hemodynamics

  After 4 week treatment with active drug intervention versus placebo

• Renal efficiency

  After 4 week treatment with active drug intervention versus placebo

• Cortical blood flow

  After 4 week treatment with active drug intervention versus placebo

• Renal arterial blood flow

  After 4 week treatment with active drug intervention versus placebo

Study Arms (2)

Ertugliflozin 15mg once daily

EXPERIMENTAL

Once daily treatment with oral ertugliflozin (steglatro) 15mg for 4 consecutive weeks.

Drug: Ertugliflozin 15 mg

Placebo

PLACEBO COMPARATOR

Once daily treatment with a placebo pill for 4 consecutive weeks.

Drug: Ertugliflozin 15 mg

Interventions

Ertugliflozin 15 mg DRUG

Once daily treatment with oral ertugliflozin 15mg for 4 consecutive weeks

Also known as: Steglatro

Ertugliflozin 15mg once daily; Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetic Nephropathies

Interventions

ertugliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. D.H. van Raalte

Study Record Dates

• First Submitted: July 9, 2019
• First Posted: July 22, 2019
• Study Start: December 10, 2020
• Primary Completion: January 9, 2023
• Study Completion: January 9, 2023
• Last Updated: May 1, 2023

Record last verified: 2023-04

Locations

NL (1)