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WithdrawnNCT04143581EMPATHYUpdated Sep 13, 2021

SGLT2 Inhibitors in Glomerular Hyperfiltration

A Phase 2 interventional study of Empagliflozin 10 MG in Obesity and Non-diabetic Chronic Kidney Disease, sponsored by Mario Negri Institute for Pharmacological Research. Withdrawn. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-09-13.

Sponsored by Mario Negri Institute for Pharmacological Research · Phase 2, Interventional, and Treatment

Why this study was withdrawn
Lack of funds
Phase
Phase 2
Study type
Interventional
Enrollment
0
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Obesity
  • Non-diabetic Chronic Kidney Disease

Keywords

  • GFR decline
  • Glomerular hyperfiltration
  • SGLT2 inhibitors
  • Residual proteinuria
  • Obesity
03

In context

Kidney Diseases

3,840 studies on the registry are indexed under Kidney Diseases; 500 are open to participants now.

Browse Kidney Diseases studies →

Lead sponsor

Mario Negri Institute for Pharmacological Research is the lead sponsor of 159 studies on the registry; 36 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Male and female ≥ 18 years old;

  2. 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;
  3. Estimated GFR > 60 ml/min/1.73m\^2 (CKD-EPI formula);
  4. Female childbearing potential and non-sterile male must agree to use a method of contraception;
  5. Written informed consent

Exclusion criteria

Exclusion Criteria:

  1. Type 1or 2 diabetic patients;
  2. Concomitant treatment with insulin or oral hypoglycemic agents;
  3. Nephrotic syndrome of any etiology;
  4. Patients with Autosomal Dominant Polycystic Kidney Disease;
  5. Symptomatic urinary tract lithiasis or obstruction;
  6. Ischemic kidney disease (because of possible excess risk of acute kidney injury upon SGLT2 inhibition associated reduction in sodium pool and kidney perfusion pressure);
  7. Rapidly progressive kidney disease defined by impairment of renal function within 2 weeks - 3 months (for the cohort of patients with residual proteinuria only) ;
  8. Active systemic autoimmune diseases;
  9. Treatment for glomerulopathies or systemic diseases with steroids or any other immunosuppressive agent within one year;
  10. Specific contraindication to SGLT2 inhibitor therapy;
  11. Heart failure with or without decreased systolic function;
  12. Uncontrolled hypertension or symptomatic hypotension;
  13. History of malignancy within 5 years of screening;
  14. Inability to fully understand the possible risks and benefits related to study participation;
  15. 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;
  16. If male, the subject intends to donate sperm while on the study this study or for 90 days after last dose;
  17. Alcohol and drug abuse;
  18. Participation in another interventional clinical trial within the 4 weeks prior to screening.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
0 participants (actual)

Study arms

  • Experimental
    IMP

    Drug: Empagliflozin 10 MG

Interventions

  • DrugEmpagliflozin 10 MG

    Empagliflozin 10 mg/die for 28 days

    Also known as: Jardiance

06

What researchers measure

Primary outcomes

  1. Measured Glomerular Filtration Rate (GFR)

    GFR will be measured by the iohexol plasma clearance technique

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

Secondary outcomes

  1. 24 hour urinary output

    last of three consecutive collections

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  2. 24 hour urinary protein excretion

    mean of the measurement in three consecutive 24-hour urine collection

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  3. 24 hour urinary albumin excretion

    mean of the measurement in three consecutive 24-hour urine collection

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  4. 24 hour urinary urea excretion

    last of three consecutive collections

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  5. 24 hour urinary phosphate excretion

    last of three consecutive collections

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  6. 24 hour urinary sodium excretion

    last of three consecutive collections

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  7. 24 hour urinary glucose excretion

    last of three consecutive collections

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  8. 24 hour urinary potassium excretion

    last of three consecutive collections

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  9. 24 hour urinary uric acid excretion

    last of three consecutive collections

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  10. 24 hour urinary creatinine excretion

    last of three consecutive collections

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Glucose disposal rate

    Performed by hyperinsulinemic euglycemic clamp and by standard oral glucose load and HOMA index;

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  18. Glucose tolerance

    Performed by hyperinsulinemic euglycemic clamp and by standard oral glucose load and HOMA index;

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  19. Office blood pressure

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  20. Office heart rate

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  21. 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

  22. 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

  23. Pulse wave velocity

    These parameters will be measured by tonometry

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  24. other marker of vascular stiffness

    These parameters will be measured by tonometry

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

  25. Indices of Quality of Life: questionnaire SF-36

    By submission of validate questionnaire

    Time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period

07

Study locations

No study locations are listed for this record.

08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 13, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04143581
Lead sponsor
Mario Negri Institute for Pharmacological Research
Collaborators
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Oct 29, 2019
Start date
Sep 3, 2021
Primary completion
Sep 3, 2021
Completion
Sep 3, 2021
Last update
Sep 13, 2021

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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