Efficacy of Double vs Standard Empapagliflozin Dose for METabolic syndromE tReatment

Metabolic Syndrome Clinical Trial

— DEMETER  

Official title:

Efficacy of Double vs Standard Empapagliflozin Dose for METabolic syndromE tReatment (DEMETER - SIRIO 11) Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05905965
• Other study ID #: DEMETER
• Status: Recruiting
• Phase: Phase 3
• Start date: May 1, 2023
• Est. completion date: March 31, 2025

Study information

• Verified date: June 2023
• Source: Collegium Medicum w Bydgoszczy
• Contact: Jacek Kubica, Prof.
• Phone: +48 525854023
• Email: jkubica[@]cm.umk.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: March 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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) < 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

Related Conditions & MeSH terms

• Metabolic Syndrome
• Syndrome

Intervention

Drug:
• Empagliflozin 20 mg
Patients receiving empagliflozin 20 mg daily - experimental arm
• Empagliflozin 10 mg
Patients receiving empagliflozin 10 mg daily - control arm

Locations

Country	Name	City	State
Poland	Cardiology Department, Dr. A. Jurasz University Hospital	Bydgoszcz	Cuiavian-Pomeranian

Sponsors (1)

Lead Sponsor	Collaborator
Collegium Medicum w Bydgoszczy

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	BMI (Body Mass Index)	change in BMI between study arms	0-6 months
Primary	concentration of HbA1c (glycated hemoglobin)	change in glycated hemoglobin plasma concentration between study arms	0-6 months
Secondary	concentration of LDL-C (low density cholesterol serum concentration)	change in low density cholesterol serum concentration between study arms	0-6 months
Secondary	concentration of triglycerides	change in triglycerides serum concentration between study arms	0-6 months
Secondary	concentration of CRP (c-reactive protein)	change in CRP serum concentration between study arms	0-6 months
Secondary	concentration of NT-proBNP	change in NT-pro BNP serum concentration between study arms	0-6 months
Secondary	LVEF - left ventricle ejection fraction (echocardiography)	change in LVEF (presented in percentage) between study arms	0-6 months
Secondary	body composition analysis - body fat mass [kg]	evaluation of body fat mass [kg] change throughout the study	0-6 months
Secondary	body composition analysis - body fat mass [%]	evaluation of body fat mass [%] change throughout the study	0-6 months
Secondary	body composition analysis - lean body mass [kg]	evaluation of lean body mass [kg] change throughout the study	0-6 months
Secondary	body composition analysis - lean body mass [%]	evaluation of lean body mass [%] change throughout the study	0-6 months
Secondary	body composition analysis - skeletal muscle mass [kg]	evaluation of skeletal muscle mass [kg] change throughout the study	0-6 months
Secondary	body composition analysis - total body water [liters]	evaluation of total body water [liters] change throughout the study	0-6 months
Secondary	body composition analysis - total body water [%]	evaluation of total body water [%] change throughout the study	0-6 months
Secondary	body composition analysis - extracellular water [liters]	evaluation of extracellular water [liters] change throughout the study	0-6 months
Secondary	body composition analysis - extracellular water [%]	evaluation of extracellular water [%] change throughout the study	0-6 months
Secondary	body composition analysis - hydration [%]	evaluation of hydration [%] change throughout the study	0-6 months
Secondary	body composition analysis - visceral fat level [liters]	evaluation of visceral fat level [liters] change throughout the study	0-6 months
Secondary	level of maximal oxygen uptake (VO2max) measured in ergospirometry	change in VO2 max between study arms	0-6 months
Secondary	waist-hip ratio (WHR)	change in waist-hip ratio between study arms	0-6 months
Secondary	liver steatosis assessment (LSA) by computed tomography (CT)	evaluation of liver steatosis assessment (LSA) assessed with computed tomography (CT), between study arms throughout the study	0-6 months
Secondary	major adverse cardiovascular events - MACE	rate of MACE (based on medical history: heart attack, stroke, death) between study arms throughout the study	0-6 months
Secondary	cardiovascular hospitalizations	rate of cardiovascular hospitalizations between study arms	0-6 months