Clinical trial NCT05905965: Efficacy of Double vs Standard Empapagliflozin Dose for METabolic syndromE tReatment
Official title: Efficacy of Double vs Standard Empapagliflozin Dose for METabolic syndromE tReatment (DEMETER - SIRIO 11) Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metabolic Syndrome
Keywords: metabolic syndrome
empagliflozin
adherence
Lead sponsor: Collegium Medicum w Bydgoszczy
Sponsor class: OTHER
First posted: 2023-06-15
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The DEMETER - SIRIO 11 study is a phase III, multicenter, randomized, open-labled, investigator-initiated clinical trial with a 6 month follow-up.

The study population will include 200 subjects with diagnosis of metabolic syndrome.

All enrolled patients (nn=200) will be randomly assigned in 1:1 ratio to one of the two study arms:

1. Empagliflozin 20 mg - experimental arm
2. Empagliflozin 10 mg - control arm. Primary co-endpoints of the study include: BMI and HbA1c. Secondary endpoints include: LDL-C, triglycerides, CRP, NT-proBNP, LVEF (echocardiography), body composition, VO2max (ergospirometry), waist-hip ratio (WHR), liver steatosis assessment (LSA) by computed tomography (CT), major adverse cardiovascular events - MACE (based on medical history: heart attack, stroke, death), cardiovascular hospitalizations.

Detailed description: The DEMETER - SIRIO 11 study is a phase III, multicenter, randomized, open-labled, investigator-initiated clinical trial with a 6 month follow-up.

The study population will include 200 subjects with diagnosis of metabolic syndrome.

All enrolled patients (nn=200) will be randomly assigned in 1:1 ratio to one of the two study arms:

1. Empagliflozin 20 mg - experimental arm
2. Empagliflozin 10 mg - control arm.

Primary co-endpoints of the study include: BMI and HbA1c.

Secondary endpoints include:

* LDL-C,
* triglycerides,
* CRP,
* NT-proBNP,
* LVEF (echocardiography),
* body composition,
* VO2max (ergospirometry),
* waist-hip ratio (WHR),
* liver steatosis assessment (LSA) by computed tomography (CT),
* major adverse cardiovascular events - MACE (based on medical history: heart attack, stroke, death),
* cardiovascular hospitalizations.

Other variables that are scheduled to be analyzed: central arterial pressure, pulse wave propagation speed, ABPM (ambulatory blood pressure monitoring), endothelial function assessment by Endopath, autonomic nervous system assessment (ANSA) by Task Force Touch CARDIO (TFTC), exercise tolerance, thickness of the adipose tissue (skin fold), blood samples: blood count, serum creatinine and eGFR, ALT, AST, GGTP, total cholesterol, HDL-C, uric acid, plasma concentration of calcium, phosphate, parathormon, 25-OH-D3, cystatin C, erythropoietin; morning urine: N-acetyl-beta-D-glucosaminidase, sodium/creatinine ratio, calcium/creatinine ratio, albumin/creatinine ratio. Moreover, functioning in chronic disease and adherence to medication and diet will be assessed with dedicated questionairies (FCIS, ACDS, ACDS diet).

Eligibility criteria: Inclusion Criteria:

* diagnosis of metabolic syndrome as follows: the presence of obesity (waist circumference ≥ 88 cm in women; ≥102 cm or body mass index (BMI) ≥30 kg/m2) and two of the three following criteria:

  1. high blood pressure (systolic blood pressure - in-office measurement: ≥ 130 and/or diastolic blood pressure ≥85 mm Hg or systolic blood pressure - ambulatory measurement: ≥130 and/or diastolic blood pressure ≥ 80 mm Hg) or on anti-hypertensive treatment;
  2. impaired glucose metabolism (fasting glucose ≥100 mg/dL or ≥ 140 mg/dL after 120 min in oral glucose tolerance test or HbA1c ≥5.7%) or on glucose-lowering drug treatment;
  3. elevated non-high-density lipoprotein (non-HDL ≥130 mg/dL) cholesterol level (atherogenic dyslipidemia) or on lipid-lowering drug treatment

Exclusion Criteria:

* current treatment with SGLT2 inhibitor
* chronic kidney disease with estimated glomerular filtration rate (eGFR) \&lt; 30 mL/min or on dialysis
* severely impaired liver function
* known hypersensitivity to the active empagliflozin or to any of the excipients contained in Jardiance
* history of ketoacidosis
* diabetes treated with insulin
* pregnancy
* decompensated heart failure
* acute coronary syndrome
* active thromboembolic disease
* current treatment for neoplastic disease
* active inflammatory disease within 1 month prior to enrollment
* expected lifetime \<1 year
* non-cooperative patients

Primary outcomes:
measure: BMI (Body Mass Index)
timeFrame: 0-6 months
measure: concentration of HbA1c (glycated hemoglobin)
timeFrame: 0-6 months
Secondary outcomes:
measure: concentration of LDL-C (low density cholesterol serum concentration)
timeFrame: 0-6 months
measure: concentration of triglycerides
timeFrame: 0-6 months
measure: concentration of CRP (c-reactive protein)
timeFrame: 0-6 months
measure: concentration of NT-proBNP
timeFrame: 0-6 months
measure: LVEF - left ventricle ejection fraction (echocardiography)
timeFrame: 0-6 months
measure: body composition analysis - body fat mass [kg]
timeFrame: 0-6 months
measure: body composition analysis - body fat mass [%]
timeFrame: 0-6 months
measure: body composition analysis - lean body mass [kg]
timeFrame: 0-6 months
measure: body composition analysis - lean body mass [%]
timeFrame: 0-6 months
measure: body composition analysis - skeletal muscle mass [kg]
timeFrame: 0-6 months
measure: body composition analysis - total body water [liters]
timeFrame: 0-6 months
measure: body composition analysis - total body water [%]
timeFrame: 0-6 months
measure: body composition analysis - extracellular water [liters]
timeFrame: 0-6 months
measure: body composition analysis - extracellular water [%]
timeFrame: 0-6 months
measure: body composition analysis - hydration [%]
timeFrame: 0-6 months
measure: body composition analysis - visceral fat level [liters]
timeFrame: 0-6 months
measure: level of maximal oxygen uptake (VO2max) measured in ergospirometry
timeFrame: 0-6 months
measure: waist-hip ratio (WHR)
timeFrame: 0-6 months
measure: liver steatosis assessment (LSA) by computed tomography (CT)
timeFrame: 0-6 months
measure: major adverse cardiovascular events - MACE
timeFrame: 0-6 months
measure: cardiovascular hospitalizations
timeFrame: 0-6 months
Other outcomes:
Locations:
city: Bydgoszcz
country: Poland
facility: Cardiology Department, Dr. A. Jurasz University Hospital
state: Cuiavian-Pomeranian
Study officials:
affiliation: Collegium Medicum w Bydgoszczy
name: Jacek Kubica, Prof.
role: PRINCIPAL_INVESTIGATOR
References: