DAPAgliflozin Sodium Water glucosE EffecTs in Patients at High Cardiovascular Risk

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Health Network, Toronto
• Collaborators: MOUNT SINAI HOSPITAL; Sunnybrook Health Sciences Centre
• Treatments: 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol; Dapagliflozin

Criteria

Inclusion Criteria:

1. eGFR ≥30 ml/min/1.73m2

2. In patients with type 2 diabetes, HbA1c <12.0%

3. Body Mass Index (BMI) 18.5-45.0 kg/m2

4. Blood pressure < or = 160/100 at screening (sitting)

5. Stable dose of maximally tolerated ACE inhibitor, angiotensin receptor blocker or renin inhibitor for at least 30 days

6. Stable diuretic dose for at least 14 days prior to baseline study Visit

7. 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).

Exclusion Criteria:

1. Type 1 Diabetes

2. Iodine intolerance

3. Hypersensitivity or allergy to dapagliflozin

4. Use of an SGLT2 inhibitor within 30 days

5. Leukocyte and/or nitrite positive urinalysis that is untreated

6. Severe hypoglycaemia within 1 month prior to screening

7. Unstable coronary artery disease with acute coronary syndrome, percutaneous intervention or bypass surgery within 3 months

8. Clinically significant valvular disease in the opinion of the investigator

9. Congestive heart failure secondary to an infiltrative cardiomyopathic process (for example amyloid) or pericardial constriction

10. Bariatric surgery or other surgeries that induce chronic malabsorption within 1 year;

11. Anti-obesity drugs or diet regimen and unstable body weight three months prior to screening;

12. Treatment with systemic corticosteroids

13. Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells

14. Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control

15. Participation in another trial with an investigational drug within 30 days of informed consent

16. Alcohol or drug abuse within three months prior to informed consent that would interfere with trial participation or any ongoing clinical condition that would jeopardize subject safety or study compliance based on investigator judgement

17. Liver disease, defined by serum levels of alanine transaminase, aspartate transaminase, or alkaline phosphatase >3 x upper limit of normal as determined during screening

18. Medical history of cancer or treatment for cancer in the last five years prior to screening, aside from uncomplicated basal cell or squamous cell carcinoma;

19. Unstable or rapidly progressive renal disease as per investigator judgement

20. Intolerance or sensitivity to SGLT2 inhibitors