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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

25 Jul 2023 → 30 Nov 2025

Decision date (initial)

2024-10-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-510257-42-01

EudraCT number

2021-005474-25

WHO UTN

U1111-1305-2343

ClinicalTrials.gov

NCT05727579

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy

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.

Secondary objectives 1

1. To investigate the efficacy of ertugliflozin 15 mg daily, versus placebo, in overweight/obese adults with type 2 diabetes to reduce the hypertensive effects of a high-sodium diet (250 mmol per day) versus participant’s normal diet (170 mmol/per day).

Conditions and MedDRA coding

Type 2 diabetes

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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 Metforming, SU, DPP4-inhibitors, or insulin. • All participants need to be on a stable dose of RAS blocker

Exclusion criteria 1

1. 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: o Acute coronary syndrome o Chronic heart failure (New York Heart Association grade II-IV) o 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 1

1. GFR by iohexol clearance  Hematocrit  Office blood pressure  Kidney oxygenation  Parameters of intra kidney hemodynamic function including ERPF by p-aminohippurate (PAH) clearance and renal vascular resistance  Body anthropometrics  Fasting plasma glucose  Albumin excretion rate (24 hour)  24-hr urinary glucose excretion  Urinary and plasma biomarkers

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC

Sponsor organisation

Amsterdam UMC

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC

Contact name

D.H. van Raalte

Public contact point

Organisation

Amsterdam UMC

Contact name

D.H. van Raalte

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications