ObesityPhase 2EMPATHYNCT04143581
SGLT2 Inhibitors in Glomerular Hyperfiltration
A Phase 2 study testing Empagliflozin 10 MG in people with Obesity and Non-diabetic Chronic Kidney Disease, run by Mario Negri Institute for Pharmacological Research.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Obesity, Non-diabetic Chronic Kidney Disease
- What is being tested?
- Empagliflozin 10 MG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 3 Sep 2021to 3 Sep 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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);
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- 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.
About this study
Official title: 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.
- Conditions
- Obesity, Non-diabetic Chronic Kidney Disease
- Being tested
- Empagliflozin 10 MG
- Keywords
- GFR decline, Glomerular hyperfiltration, SGLT2 inhibitors, Residual proteinuria, Obesity
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 10 MGDrug
Also called Jardiance
Empagliflozin 10 mg/die for 28 days
| Study group | Role | What they receive |
|---|---|---|
| IMP | Experimental | Not described Receives: Drug: Empagliflozin 10 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measured Glomerular Filtration Rate (GFR)
GFR will be measured by the iohexol plasma clearance technique
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
Secondary outcomes (25)
24 hour urinary output
last of three consecutive collections
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
24 hour urinary protein excretion
mean of the measurement in three consecutive 24-hour urine collection
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
24 hour urinary albumin excretion
mean of the measurement in three consecutive 24-hour urine collection
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
24 hour urinary urea excretion
last of three consecutive collections
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
24 hour urinary phosphate excretion
last of three consecutive collections
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
24 hour urinary sodium excretion
last of three consecutive collections
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
24 hour urinary glucose excretion
last of three consecutive collections
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
24 hour urinary potassium excretion
last of three consecutive collections
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
24 hour urinary uric acid excretion
last of three consecutive collections
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
24 hour urinary creatinine excretion
last of three consecutive collections
Measured: 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
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
Fractional clearance of albumin calculated by standard formulas
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
Fractional clearance of sodium calculated by standard formulas
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
Fractional clearance of potassium calculated by standard formulas
Measured: 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
Measured: 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
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
Glucose disposal rate
Performed by hyperinsulinemic euglycemic clamp and by standard oral glucose load and HOMA index;
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
Glucose tolerance
Performed by hyperinsulinemic euglycemic clamp and by standard oral glucose load and HOMA index;
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
Office blood pressure
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
Office heart rate
Measured: 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
Measured: 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
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
Pulse wave velocity
These parameters will be measured by tonometry
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
other marker of vascular stiffness
These parameters will be measured by tonometry
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
Indices of Quality of Life: questionnaire SF-36
By submission of validate questionnaire
Measured: Changes from baseline to the end of one-month treatment period and one-month recovery period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2019
- Study start3 Sep 2021
- Primary completion3 Sep 2021
- Study completion3 Sep 2021
Why it stopped: Lack of funds
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- OFF/ON/OFF design
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mario Negri Institute for Pharmacological Research
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04143581
- Sponsor's protocol ID
- EMPATHY
- Other IDs
- 2019-004152-10, 2019
- Acronym
- EMPATHY
- Status last verified
- Sep 2021
- First submitted
- 25 Oct 2019
- Last updated
- 13 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04143581
- Acronym / sponsor ID
- EMPATHY / EMPATHY
- Conditions
- Obesity, Non-diabetic Chronic Kidney Disease
- Keywords
- GFR decline, Glomerular hyperfiltration, SGLT2 inhibitors, Residual proteinuria, Obesity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funds
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim
- Study start
- 3 Sep 2021 (actual)
- Primary completion
- 3 Sep 2021 (actual)
- Study completion
- 3 Sep 2021 (actual)
- First posted
- 29 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- OFF/ON/OFF design
| Arm | Type | Receives |
|---|---|---|
| IMP | Experimental | Drug: Empagliflozin 10 MG |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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:
- 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
Key exclusion criteria (18 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empagliflozin 10 MGAlso: JardianceEmpagliflozin 10 mg/die for 28 days | Drug | IMP |
Primary outcome
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
25 secondary outcomes
24 hour urinary output
Time frame: 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
24 hour urinary albumin excretion
Time frame: 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
24 hour urinary phosphate excretion
Time frame: 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
24 hour urinary glucose excretion
Time frame: 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
24 hour urinary uric acid excretion
Time frame: 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
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
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
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
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
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
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
Glucose disposal rate
Time frame: 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
Office blood pressure
Time frame: 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
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
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
Pulse wave velocity
Time frame: 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
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Empagliflozin 10 MG in people with Obesity and Non-diabetic Chronic Kidney Disease, run by Mario Negri Institute for Pharmacological Research.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measured Glomerular Filtration Rate (GFR) (time frame: Changes from baseline to the end of one-month treatment period and one-month recovery period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2021.