DiEtary Sodium Intake Effects on Ertugliflozin-induced Changes in GFR, reNal Oxygenation and Systemic Hemodynamics: the DESIGN Study

NCT ID: NCT05727579

Last Updated: 2023-05-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-01
• Study Completion Date: 2025-03-01

Brief Summary

SGLT2 inhibitors such as ertugliflozin improve blood pressure and kidney outcomes in people living with diabetes through incompletely understood mechanisms, however, not all patients treated with SGLT2 inhibition have improved outcomes. Changes in kidney sodium handling is among the mechanisms by which SGLT2 inhibition may reduce blood pressure and drive beneficial kidney outcomes. This process is heavily dependent on daily sodium intake by patients receiving SGLT2 inhibitor treatment. In this study, the effect of daily sodium intake on SGLT2-inhibitor induced physiological effect is studied, including blood pressure regulation and kidney physiology.

Conditions

Diabetes Mellitus; Diabetic Kidney Disease; Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

low-sodium diet; placebo

Group Type: OTHER

Salt-Diet and/or Ertugliflozin

Intervention Type: OTHER

The interventions consist of an determined amount of dietary sodium intake in combination with either Ertugliflozin 15mg once daily or placebo

low-sodium diet; ertugliflozin 15 once daily

Group Type: OTHER

Salt-Diet and/or Ertugliflozin

Intervention Type: OTHER

The interventions consist of an determined amount of dietary sodium intake in combination with either Ertugliflozin 15mg once daily or placebo

high-sodium diet; placebo

Group Type: OTHER

Salt-Diet and/or Ertugliflozin

Intervention Type: OTHER

The interventions consist of an determined amount of dietary sodium intake in combination with either Ertugliflozin 15mg once daily or placebo

High-sodium diet; ertugliflozin 15 mg once daily

Group Type: OTHER

Salt-Diet and/or Ertugliflozin

Intervention Type: OTHER

The interventions consist of an determined amount of dietary sodium intake in combination with either Ertugliflozin 15mg once daily or placebo

Interventions

Salt-Diet and/or Ertugliflozin

The interventions consist of an determined amount of dietary sodium intake in combination with either Ertugliflozin 15mg once daily or placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adults with previously diagnosed T2DM according to American Diabetes Association (ADA) criteria
• HbA1c 6.5-10%
• Age 35-80 years of age
• Overweight or obese with BMI: >25 kg/m2
• We will make every effort to enrol participants of all races/ethnicities."
• Both sexes (females must be post-menopausal; no menses >1 year; in case of doubt, Follicle-Stimulating Hormone (FSH) will be determined with cut-off defined as >31 U/L)
• Ability to provide signed and dated, written informed consent prior to any study procedures
• Estimated GFR 60-90 ml/min/1.73m2 by CKD-EPI matching the eGFR range of most participants in VERTIS-CV
• Sodium intake at baseline < 200 mmol/day
• UACR < 30 mg/mmol
• All participants need to be on a stable dose of Diabetes medication, including Metformin, SU, insulin
• All participants need to be on a stable dose of RAS inhibition

Exclusion Criteria

History of unstable or rapidly progressing renal disease

• Estimated GFR <60 mL/min/1.73m2 or eGFR > 90 mL/min/1.73m2 determined by CKD-EPI
• UACR > 30 mg/mmol
• Current/chronic use of the following medication: SGLT2 inhibitors, TZD, GLP-1RA, glucocorticoids, immune suppressants, antimicrobial agents, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). Subjects on diuretics will only be excluded when these drugs cannot be stopped for the duration of the study.
• Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications (i.e. sports injury, headache or back ache). However, no such drug can be taken within a timeframe of 2 weeks prior to renal testing
• History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g. emergency room visit and/or hospitalization) within 1 month prior to the Screening visit.
• Current urinary tract infection and active nephritis
• Recent (<6 months) history of cardiovascular disease, including:

• Acute coronary syndrome
• Chronic heart failure (New York Heart Association grade II-IV)
• Stroke or transient ischemic neurologic disorder
• Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
• History of or actual malignancy (except basal cell carcinoma)
• History of or actual severe mental disease
• Substance abuse (alcohol: defined as >4 units/day)
• Allergy to any of the agents used in the study
• Individuals who are investigator site personnel, directly affiliated with the study, or are immediate (spouse, parent, child, or sibling, whether biological or legally adopted) family of investigator site personnel directly affiliated with the study
• Inability to understand the study protocol or give informed consent

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: collaborator

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: lead

Responsible Party

D van Raalte

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Daniel van Raalte, MD PhD

Role: CONTACT

d.vanraalte@amsterdamumc.nl

+31204440534

Other Identifiers

DC2022ERTU

Identifier Type: -

Identifier Source: org_study_id