- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04143581
SGLT2 Inhibitors in Glomerular Hyperfiltration (EMPATHY)
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
Glomerular hyperfiltration is a major risk factor for accelerated glomerular filtration rate (GFR) decline and renal and cardiovascular events despite optimized conservative therapy with blood pressure and blood glucose (in diabetics) lowering medications and inhibitors of the Renin Angiotensin System (RAS) such as Angiotensin Converting Enzyme (ACE) inhibitors and/or Angiotensin Receptor Blockers (ARBs).
Progressive GFR decline initiated and sustained by glomerular hyperfiltration in subjects with diabetes, unhealthy obesity, hypertension and other risk factors, is paralleled by progressive glomerulosclerosis and loss of functioning nephrons.
The inhibition of the sodium-glucose cotransporter 2 (SGLT2) in the proximal tubular segments of the nephrons appears to be an ideal, specific intervention to inhibit the tubulo-glomerular feedback and ameliorate glomerular hyperfiltration in subjects with absolute or relative hyperfiltration associated with unhealthy obesity or proteinuric chronic kidney disease (CKD). Indeed, by reducing tubular sodium reabsorption, SGLT2 inhibitors may enhance sodium chloride delivery to the macula densa, restore pre-glomerular resistances and therefore limit glomerular hyperperfusion and consequent hyperfiltration. Moreover, because of its natriuretic effects, SGLT2 inhibition therapy might reduce the sodium overload and volume expansion which, along with secondary hypertension, may further contribute to kidney hyperperfusion and glomerular hyperfiltration in obesity and CKD.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male and female ≥ 18 years old;
Increased risk of accelerated renal function loss because of absolute or relative hyperfiltration associated with unhealthy obesity or residual proteinuria defined as:
Unhealthy obesity:
- BMI >30 kg/m^2 or 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 and <125 mg/dL
Residual proteinuria:
- Urinary protein excretion >1g/24-h to <3g/24-h despite RAS inhibitor therapy with ACE inhibitors or ARBs;
- Blood pressure in recommended targets with or without blood pressure lowering medications;
- Estimated GFR > 60 ml/min/1.73m^2 (CKD-EPI formula);
- Female childbearing potential and non-sterile male must agree to use a method of contraception;
- Written informed consent
Exclusion Criteria:
- Type 1or 2 diabetic patients;
- Concomitant treatment with insulin or oral hypoglycemic agents;
- Nephrotic syndrome of any etiology;
- Patients with Autosomal Dominant Polycystic Kidney Disease;
- Symptomatic urinary tract lithiasis or obstruction;
- Ischemic kidney disease (because of possible excess risk of acute kidney injury upon SGLT2 inhibition associated reduction in sodium pool and kidney perfusion pressure);
- Rapidly progressive kidney disease defined by impairment of renal function within 2 weeks - 3 months (for the cohort of patients with residual proteinuria only) ;
- Active systemic autoimmune diseases;
- Treatment for glomerulopathies or systemic diseases with steroids or any other immunosuppressive agent within one year;
- Specific contraindication to SGLT2 inhibitor therapy;
- Heart failure with or without decreased systolic function;
- Uncontrolled hypertension or symptomatic hypotension;
- History of malignancy within 5 years of screening;
- Inability to fully understand the possible risks and benefits related to study participation;
- 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;
- If male, the subject intends to donate sperm while on the study this study or for 90 days after last dose;
- Alcohol and drug abuse;
- Participation in another interventional clinical trial within the 4 weeks prior to screening.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: IMP
|
Empagliflozin 10 mg/die for 28 days
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Measured Glomerular Filtration Rate (GFR)
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
GFR will be measured by the iohexol plasma clearance technique
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
24 hour urinary output
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
last of three consecutive collections
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
24 hour urinary protein excretion
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
mean of the measurement in three consecutive 24-hour urine collection
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
24 hour urinary albumin excretion
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
mean of the measurement in three consecutive 24-hour urine collection
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
24 hour urinary urea excretion
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
last of three consecutive collections
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
24 hour urinary phosphate excretion
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
last of three consecutive collections
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
24 hour urinary sodium excretion
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
last of three consecutive collections
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
24 hour urinary glucose excretion
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
last of three consecutive collections
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
24 hour urinary potassium excretion
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
last of three consecutive collections
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
24 hour urinary uric acid excretion
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
last of three consecutive collections
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
24 hour urinary creatinine excretion
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
last of three consecutive collections
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Fractional clearance of total protein calculated by standard formulas
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
|
Fractional clearance of albumin calculated by standard formulas
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
|
Fractional clearance of sodium calculated by standard formulas
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
|
Fractional clearance of potassium calculated by standard formulas
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
|
Fractional clearance of uric acid calculated by standard formulas
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
|
Fractional clearance of free water calculated by standard formulas
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
|
Glucose disposal rate
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Performed by hyperinsulinemic euglycemic clamp and by standard oral glucose load and HOMA index;
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Glucose tolerance
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Performed by hyperinsulinemic euglycemic clamp and by standard oral glucose load and HOMA index;
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Office blood pressure
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
|
Office heart rate
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
|
24 hour (day-time and night-time) blood pressure monitoring
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
|
24 hour (day-time and night-time) heart rate monitoring
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
|
Pulse wave velocity
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
These parameters will be measured by tonometry
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
other marker of vascular stiffness
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
These parameters will be measured by tonometry
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Indices of Quality of Life: questionnaire SF-36
Time Frame: Changes from baseline to the end of one-month treatment period and one-month recovery period
|
By submission of validate questionnaire
|
Changes from baseline to the end of one-month treatment period and one-month recovery period
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- EMPATHY
- 2019-004152-10 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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