Evaluating the Short-Term Renal and Systemic Effects of SGLT2 Inhibition in Non-Diabetic Patients at Risk of Accelerated GFR Decline Because of Glomerular Hyperfiltration: a sequential OFF-ON-OFF Study with One-Month Empagliflozin Therapy Followed by One-Month Recovery Period

Phase 1

• Conditions: ObesityRenal chronic disease; MedDRA version: 20.0Level: PTClassification code 10029883Term: ObesitySystem Organ Class: 10027433 - Metabolism and nutrition disorders; MedDRA version: 21.1Level: LLTClassification code 10009119Term: Chronic renal failureSystem Organ Class: 100000004857; Therapeutic area: Diseases [C] - Male diseases of the urinary and reproductive systems [C12]

• Registration Number: EUCTR2019-004152-10-IT
• Lead Sponsor: IRCCS- ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-17
• Last Update Posted: 8 August 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 0

Inclusion Criteria

- Male and female = 18 years old;
- Increased risk of accelerated renal function loss because of absolute or relative hyperfiltration associated with unhealthy (abdominal) obesity or residual proteinuria defined as:
Unhealthy obesity:
- Waist circumference =94 cm in males and = 80 cm in females
Metabolic syndrome, defined as the presence of at least three of the following criteria:
- Blood pressure>140/90 mmHg or controlled blood pressure under current antihypertensive treatment
- Triglyceride levels >150 mg/dL
- HDL<40 mg/dL in males <50 mg/dL in females
- Fasting blood glucose > 100 mg/dL
Residual proteinuria:
- Urinary protein excretion >1g/24-h to <3g/24-h despite stable and continuous RAS inhibitor therapy with ACE inhibitors or ARBs for at least three months Blood pressure in recommended targets and stable treatment with blood pressure lowering medications for at least three months
- Female childbearing potential and non-sterile male must agree to use a method of contraception according to 2014 CTFG Recommendations related to contraception and pregnancy testing in clinical trials;
- Written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22

Exclusion Criteria

Exclusion Criteria
1. Type 1or 2 diabetic patients;
2. Fasting blood glucose > 125 mg/dl and/or concomitant treatment with insulin or oral hypoglycemic agents;
3. Estimated GFR = 60 ml/min/1.73m2 (CKD-EPI formula);
4. Reversible causes of transient increases of proteinuria including infection, fever, strenuous physical exercise
5. Nephrotic syndrome of any etiology;
6. Patients with Autosomal Dominant Polycystic Kidney Disease;
7. Symptomatic urinary tract lithiasis or obstruction;
8. Ischemic kidney disease (because of possible excess risk of acute kidney injury upon SGLT2 inhibition associated reduction in sodium pool and kidney perfusion pressure);
9. Rapidly progressive kidney disease defined by impairment of renal function within 2 weeks – 3 months (for the cohort of patients with residual proteinuria only) ;
10. Active systemic autoimmune diseases;
11. Treatment for glomerulopathies or systemic diseases with steroids or any other immunosuppressive agent within one year;
12. Hypersensitivity to the active principle (empagliflozin) or any of the excipients (e.g. lactose);;
13. Heart failure with or without decreased systolic function;
14. Uncontrolled hypertension or symptomatic hypotension;
15. History of malignancy within 5 years of screening;
16. Inability to fully understand the possible risks and benefits related to study participation;
17. If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 90 days after last dose; or intending to donate ova during such time period;
18. If male, the subject intends to donate sperm while on the study this study or for 90 days after last dose;
19. Alcohol and drug abuse;
20. Participation in another interventional clinical trial within the 4 weeks prior to screening.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified