DAPAgliflozin Sodium Water glucosE EffecTs in Patients at High Cardiovascular Risk

NCT04258371 | Unknown Phase 2

• 1 other identifier: 18-5597
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to elucidate the impact of SGLT2 inhibition on peripheral vascular function, renal function, fluid volume, neurohormonal activation and inflammatory/fibrotic pathways in patients with T2D at high cardiovascular risk and non-T2D patients.

Conditions

Cardiovascular Risk Factor

Keywords

SGLT2 inhibition; Cardiovascular risk; Dapagliflozin

Outcome Measures

Primary Outcomes (2)

• Arterial stiffness

  Measured using a Sphygmocor device

  Acute (1 week)

• Arterial stiffness

  Measured using a Sphygmocor device

  Chronic (12 weeks)

Secondary Outcomes (28)

• Glomerular filtration rate

  Glomerular Filtration Rate (GFR, based on plasma iohexol clearance) will be measured at 2 time points: acute (1 week) and chronic (12 weeks)

• Flow mediated dilation

  Outcome will remeasured at 2 time points: acute (1 week) and chronic (12 weeks)

• Nitroglycerin mediated dilation

  Outcome will remeasured at 2 time points: acute (1 week) and chronic (12 weeks)

• Systolic blood pressure

  Outcome will remeasured at 2 time points: acute (1 week) and chronic (12 weeks)

• Diastolic blood pressure

  Outcome will remeasured at 2 time points: acute (1 week) and chronic (12 weeks)

Other Outcomes (3)

• Number of hypoglycaemic episodes

  Throughout study completion, an average of 12 weeks

• Serious adverse events

  Throughout study completion, an average of 12 weeks

• Drug related adverse events

  Throughout study completion, an average of 12 weeks

Study Arms (2)

Dapagliflozin Treatment Arm

EXPERIMENTAL

Dapagliflozin Tablets Total Dose 10mg daily for 12 weeks

Drug: Dapagliflozin 10 MG

Placebo Arm

PLACEBO COMPARATOR

Placebo Matching Dapagliflozin Tablet for 12 weeks

Drug: Placebo oral tablet

Interventions

Dapagliflozin 10 MG DRUG

Dapagliflozin Tablets Total Dose 10mg daily for 12 weeks

Dapagliflozin Treatment Arm

Placebo oral tablet DRUG

Placebo once daily for 12 weeks

Placebo Arm

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• eGFR ≥30 ml/min/1.73m2
• In patients with type 2 diabetes, HbA1c \<12.0%
• Body Mass Index (BMI) 18.5-45.0 kg/m2
• Blood pressure \< or = 160/100 at screening (sitting)
• Stable dose of maximally tolerated ACE inhibitor, angiotensin receptor blocker or renin inhibitor for at least 30 days
• Stable diuretic dose for at least 14 days prior to baseline study Visit
• High cardiovascular risk: an age of 50 years or more with at least one cardiovascular coexisting condition (coronary heart disease, cerebrovascular disease, peripheral vascular disease, chronic kidney disease of stage 3 or greater, or chronic heart failure of New York Heart Association class II or III) OR an age of 60 years or more with at least one cardiovascular risk factor, as determined by the investigator (microalbuminuria or proteinuria, hypertension and left ventricular hypertrophy, left ventricular systolic or diastolic dysfunction, or an ankle-brachial index \[the ratio of the systolic blood pressure at the ankle to the systolic blood pressure in the arm\] of less than 0.9).

You may not qualify if:

• Type 1 Diabetes
• Iodine intolerance
• Hypersensitivity or allergy to dapagliflozin
• Use of an SGLT2 inhibitor within 30 days
• Leukocyte and/or nitrite positive urinalysis that is untreated
• Severe hypoglycaemia within 1 month prior to screening
• Unstable coronary artery disease with acute coronary syndrome, percutaneous intervention or bypass surgery within 3 months
• Clinically significant valvular disease in the opinion of the investigator
• Congestive heart failure secondary to an infiltrative cardiomyopathic process (for example amyloid) or pericardial constriction
• Bariatric surgery or other surgeries that induce chronic malabsorption within 1 year;
• Anti-obesity drugs or diet regimen and unstable body weight three months prior to screening;
• Treatment with systemic corticosteroids
• Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells
• Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control
• Participation in another trial with an investigational drug within 30 days of informed consent

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Sunnybrook Health Sciences Centre: collaborator
• MOUNT SINAI HOSPITAL: collaborator

Study Sites (1)

Renal Physiology Laboratory

Toronto, Canada

RECRUITING

Related Publications (1)

• Sridhar VS, Kugathasan L, Lytvyn Y, Deng Y, Liu H, Lovblom LE, Tse J, Nardone M, Floras JS, Osuntokun T, Tobushi T, Lam RCY, Lam B, Stevens J, Burger D, Touw DJ, Heerspink HJL, Lovshin JA, Perkins BA, Cherney DZI. Cardiovascular-Kidney Effects of Dapagliflozin in Patients at Cardiovascular Risk With or Without Type 2 Diabetes: Results of a Randomized, Double-Blind, Placebo-Controlled Trial. Hypertension. 2026 Feb;83(2):e25955. doi: 10.1161/HYPERTENSIONAHA.125.25955. Epub 2025 Dec 5.

  PMID: 41347301 DERIVED

MeSH Terms

Interventions

dapagliflozin

Study Officials

• David ZI Cherney, MD PhD FRCPC

  University Health Network, Toronto General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vesta Lai, RN

CONTACT

416-340-4800; vesta.lai@uhn.ca

Yuliya Lytvyn, PhD

CONTACT

julia.lytvyn@mail.utoronto.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine, Clinician Scientist

Model Details: Patients will be randomized to 10mg PO dapagliflozin daily or matching placebo.

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: February 6, 2020
• Study Start: February 10, 2020
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: May 17, 2023

Record last verified: 2023-05

Locations

CA (1)