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

NCT05727579 | Completed Phase 4 Results FDA Drug

• 1 other identifier: DC2022ERTU
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• To Investigate the Modifying Effect of Sodium Intake on Ertugliflozin on Blood Pressure

  To investigate the modifying effects of WHO-recommended sodium intake (90 mmol per day) vs. high sodium intake (targeted at 250 mmol per day) on the effect of ertugliflozin 15 mg daily, versus placebo, on 24-hour blood pressure in overweight/obese adults with type 2 diabetes

  24 weeks

Study Arms (4)

moderate-sodium diet; placebo

PLACEBO COMPARATOR

Other: Salt-Diet and/or Ertugliflozin

moderate-sodium diet; ertugliflozin 15 once daily

ACTIVE COMPARATOR

Other: Salt-Diet and/or Ertugliflozin; Drug: Ertugliflozin 15 mg

high-sodium diet; placebo

PLACEBO COMPARATOR

Other: Salt-Diet and/or Ertugliflozin

High-sodium diet; ertugliflozin 15 mg once daily

ACTIVE COMPARATOR

Other: Salt-Diet and/or Ertugliflozin; Drug: Ertugliflozin 15 mg

Interventions

Salt-Diet and/or Ertugliflozin 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; high-sodium diet; placebo; moderate-sodium diet; ertugliflozin 15 once daily; moderate-sodium diet; placebo

Ertugliflozin 15 mg DRUG

SGLT2i

High-sodium diet; ertugliflozin 15 mg once daily; moderate-sodium diet; ertugliflozin 15 once daily

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Merck Sharp & Dohme LLC: collaborator
• University of Colorado, Denver: collaborator

Study Sites (1)

Amsterdam UMC

Amsterdam, Netherlands

Location

MeSH Terms

Conditions

Diabetes Mellitus; Diabetic Nephropathies; Hypertension

Interventions

ertugliflozin

Condition Hierarchy (Ancestors)

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; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Daniël van Raalte
• Organization: Amsterdam UMC

d.vanraalte@amsterdamumc.nl

+31-20-4440534

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Model Details: While the treatment by ertugliflozin or placebo will be blinded, the sodium interventions are open-label.

Study Record Dates

• First Submitted: January 24, 2023
• First Posted: February 14, 2023
• Study Start: July 3, 2023
• Primary Completion: November 30, 2025
• Study Completion: November 30, 2025
• Last Updated: April 15, 2026
• Results First Posted: April 15, 2026

Record last verified: 2026-03

Locations

NL (1)