SGLT2 Inhibitors in Glomerular Hyperfiltration

NCT04143581 | Withdrawn Phase 2

• 2 other identifiers: EMPATHY2019-004152-10
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Obesity; Non-diabetic Chronic Kidney Disease

Keywords

GFR decline; Glomerular hyperfiltration; SGLT2 inhibitors; Residual proteinuria; Obesity

Outcome Measures

Primary Outcomes (1)

• Measured Glomerular Filtration Rate (GFR)

  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 Outcomes (25)

• 24 hour urinary output

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

• 24 hour urinary protein excretion

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

• 24 hour urinary albumin excretion

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

• 24 hour urinary urea excretion

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

• 24 hour urinary phosphate excretion

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

Study Arms (1)

IMP

EXPERIMENTAL

Drug: Empagliflozin 10 MG

Interventions

Empagliflozin 10 MG DRUG

Empagliflozin 10 mg/die for 28 days

Also known as: Jardiance

IMP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• Boehringer Ingelheim: collaborator

MeSH Terms

Conditions

Obesity

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: OFF/ON/OFF design

Study Record Dates

• First Submitted: October 25, 2019
• First Posted: October 29, 2019
• Study Start: September 3, 2021
• Primary Completion: September 3, 2021
• Study Completion: September 3, 2021
• Last Updated: September 13, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share