DiEtary Sodium Intake Effects on Ertugliflozin-induced Changes in GFR, reNal Oxygenation and Systemic Hemodynamics: the DESIGN Study, a Randomized, Placebo-controlled, Cross-over Study With Ertugliflozin in People With Type 2 Diabetes

NCT06983054 | Recruiting Phase 4 FDA Drug

• 3 other identifiers: NL80772.029.222023-510257-42-012021-005474-25
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 2

Brief Summary

SGLT2 inhibitors have demonstrated to mitigate cardiorenal risk in people with type 2 diabetes and are likely to play an increasingly large role in the treatment of patients with diabetes, chronic kidney disease and hypertension. Yet the underlying mechanisms of its protective effects are incompletely understood and the salutary effect may be altered by dietary factors such as sodium intake. Therefore, carefully designed mechanistic trials are needed to better understand the interplay between ertugliflozin and salt intake and to potentially modify salt intake to maximize treatment response. In addition, the study could contribute to hypotheses concerning the effects of SGLT2 inhibitors in combination with other drugs that affect sodium homeostasis and could help to explain the differences in kidney outcomes observed in (outcome) trials, which include different ethnicities with potential differences in dietary habits.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• 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.

  7 months

Secondary Outcomes (1)

• Blood pressure

  7 months

Study Arms (4)

Low salt diet with SGLT2i

ACTIVE COMPARATOR

10 days of SGLT2i treatment during 20 days of low salt diet

Drug: ertugliflozine; Behavioral: low salt diet

Low salt diet with placebo

PLACEBO COMPARATOR

10 days of placebo during 20 days of low salt diet

Behavioral: low salt diet; Drug: placebo

High salt diet with SGLT2i

ACTIVE COMPARATOR

10 days of SGTL2i during 20 days of high salt diet.

Drug: ertugliflozine; Behavioral: high salt diet

High salt diet with placebo

PLACEBO COMPARATOR

10 days of placebo during 20 days of high salt diet.

Drug: placebo; Behavioral: high salt diet

Interventions

ertugliflozine DRUG

SGLT2i versus placebo

High salt diet with SGLT2i; Low salt diet with SGLT2i

low salt diet BEHAVIORAL

comparing low salt versus high salt diet

Low salt diet with SGLT2i; Low salt diet with placebo

placebo DRUG

placebo tablet

High salt diet with placebo; Low salt diet with placebo

high salt diet BEHAVIORAL

high salt diet

High salt diet with SGLT2i; High salt diet with placebo

Eligibility Criteria

• Age: 18 Years - 85 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 18 - 85 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, DPP4-inhibitors, or insulin.
• Participants suffering from hypertension need to be on a stable dose of RAS inhibitors. In case RAS inhibition is not tolerated, the participant should to be on a stable dose of other antihypertensive treatment.

You may not qualify if:

• History of unstable or rapidly progressing renal disease NL80772.029.22 / DC2022ERTU DESIGN Protocol DESIGN, Study NO. 2022.0737 Version 5.0dd22-02-2024 14 of 45
• 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 Participants should be on a stable dose of 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
• Active malignancy. History of malignancy is allowed unless the participant still has active treatment other than hormonal therapy.• History of or actual severe mental disease
• Substance abuse (alcohol: defined as \>4 units/day)

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Children's Hospital Colorado: collaborator

Study Sites (2)

Childrens hospital colorado

Denver, Colorado, 80045, United States

RECRUITING

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Diet, Sodium-Restricted

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Design

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

Study Record Dates

• First Submitted: May 13, 2025
• First Posted: May 21, 2025
• Study Start: July 25, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 21, 2025

Record last verified: 2025-05

Locations

NL (1); US (1)