Clinical trial NCT03118336: Impact of Empaglifozine on Cardiac Ectopic Fat
Official title: Impact of Empaglifozine on Cardiac Ectopic Fat
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2017-04-18
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: There is substantial evidence supporting the fact that ectopic fat accumulation is an important contributor to type 2 diabetes complications and cardiovascular risk \[1\]. Epicardial adipose tissue (EAT), located between the myocardium and the visceral layer of the pericardium has been associated with atrial fibrillation and with coronary artery disease \[2, 3\] and its abundance predicts the number of cardiac events within 8 years \[4\]. In addition, myocardial steatosis has been shown to be an independent predictor of diastolic dysfunction \[5\] \[6\]. Furthermore, in type 2 diabetic patients, bariatric surgery can reduce cardiac ectopic fat accumulation and improve cardiac function \[7\] \[8\]. When added to standard care, 10 or 25 mg/d of empagliflozin, an inhibitor of sodium-glucose cotransporter 2 (iSGLT2), significantly reduces the risk of death, cardiovascular death, and hospitalisation for heart failure among individuals with type 2 diabetes and established cardiovascular disease when compared to placebo \[9\]. The mechanisms of empagliflozin-improved cardiovascular outcomes in type 2 diabetic patients at high risk of cardiovascular events are not known. We hypotheses that empaglifozin could modulate cardiac ectopic fat and cardiac metabolism in obese type 2 diabetic patients.


Eligibility criteria: Inclusion Criteria:

* Age \> 18 years,
* Type 2 diabetes based on the disease diagnostic criteria as described by the WHO,
* HbA1c \> 7% and \< 10 %
* Stable glucose-lowering therapy for at least 3 weeks before randomization
* Estimated glomerular filtration rate \> 60/ml (MDRD)
* Signed informed consent form obtained prior to any study procedure

Exclusion Criteria:

* Evolutive or planned pregnancy during the six months
* Lactation
* Recent weight loss (\>5% of body weight within one month),
* Treatment modifying adipose distribution such as corticoids
* Acute coronary syndrome or instable angina during the last 2 months,
* MRI contraindication (metal cardiac valve, pace maker, metal foreign body, claustrophobia)

Primary outcomes:
measure: cardiac morphology
timeFrame: 12 weeks
measure: epicardial adipose tissue volume
timeFrame: 12weeks
Secondary outcomes:
measure: myocardial triglyceride
timeFrame: 12weeks
measure: hepatic triglyceride content
timeFrame: 12 weeks
measure: myocardial PCr/ATP ratio
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Marseille
country: France
facility: Assistance Publique Hopitaux de Marseille
Study officials:
affiliation: Assistance Publique Hopitaux De Marseille
name: anne dutour
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gaborit B, Ancel P, Abdullah AE, Maurice F, Abdesselam I, Calen A, Soghomonian A, Houssays M, Varlet I, Eisinger M, Lasbleiz A, Peiretti F, Bornet CE, Lefur Y, Pini L, Rapacchi S, Bernard M, Resseguier N, Darmon P, Kober F, Dutour A. Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study. Cardiovasc Diabetol. 2021 Mar 1;20(1):57. doi: 10.1186/s12933-021-01237-2.