Human Cardiac Mitochondria in Acute Endocarditis and Obesity

Obesity Clinical Trial

— MITHOM  

Official title:

Development of the Purification of Human Cardiac Mitochondria, Characterization of These Organelles and Validation of the Model in Acute Endocarditis and Obesity

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03690076
• Other study ID #: CHU-408
• Status: Recruiting
• Start date: October 9, 2018
• Est. completion date: September 30, 2020

Study information

• Verified date: February 2019
• Source: University Hospital, Clermont-Ferrand
• Contact: Lise LACLAUTRE
• Phone: 0473754963
• Email: drci[@]chu-clermontferrand.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Data about human cardiac mitochondria are cruelly lacking in the literature. However, damages of the activity of these organelles are often the source of abnormal cardiac function in several pathologies. The purpose of this study is to develop a model of purified human cardiac mitochondria, to verify the purity of these organelles and to validate the authenticity of their function in acute endocarditis and obesity, two situations known to alter their activity. Animal studies have shown that microbial infection reduced mitochondrial metabolism whereas obesity increases it. The investigator's hypotheses are the following: 1) acute endocarditis, a form of cardiac microbial infection, reduces the function of human cardiac mitochondria; 2) obesity (body mass index > 30) activates the metabolism of human cardiac mitochondria.

Description:

3 groups of patients:

• Controls: patients with normal weight (23 < BMI < 27) operated for myocardial revascularization by bypass surgery, without infarction, or for valve pathologies without endocarditis

• Endocarditis: patients with normal weight (23 < BMI < 27) carriers of endocarditis with surgery indication

• Obese: obese patients (BMI > 30) operated for myocardial revascularization by bypass surgery, without infarction, or for valve pathologies without endocarditis

Comparisons studied:

• Controls vs. endocarditis

• Controls vs. obese patients

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: September 30, 2020
• Est. primary completion date: April 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• For the controls : adult patients with normal body weight (23 < BMI < 27) necessitating a cardiac surgery with sternotomy and extracorporeal circulation for myocardial revascularization or valve replacement

• For endocarditis : adult patients with normal body weight (23 < BMI < 27) and endocarditis of bacterial origin necessitating a cardiac surgery with sternotomy and extracorporeal circulation in order to cure a major valve regurgitation or vegetation with higher size than 15 mm with embolic risk

• For obese patients: adult patients with high body weight (BMI > 30 and waist to hip ration > or = 1 for men and 0.85 for women) necessitating a cardiac surgery with sternotomy and extracorporeal circulation for myocardial revascularization or valve replacement

For all the patients:

• Ability to furnish an enlightened agreement

• Menbership of the French social security insurance

Exclusion Criteria:

• Criteria linked to the surgery:

• Surgery of pressing emergency

• Aortic dissection

• Redux surgery

Criteria linked to the patient:

• Protocol refusal

• Protected adult patients

• Previous psychiatric pathology including known addiction states

• Physical or intellectual inability

• Preexisting pathologies such as respiratory failure

• Cardiac failure (ejection fraction < 30% pulmonary hypertenstion > 80 mmHg); aortic counterpulsation; pre-operatory cardiogenic shock

• Severe acute or chronic renal failure with creatinine clearance < 40 ml/min

• Inherited dyslipidemia

• Previous cardiac or thoracic surgery with pericardium opening

• Severe hepatic failure and severe chronic hepatic pathologies

• Evolving neoplasia

• Patients with long course corticoid treatment and with inflammatory diseases

• Patients with double anti-platelet treatment not stopped 48h before the surgery

• Protected people not involved in the study: pregnant women, nursing women, guardianship, deprived of liberty,

Related Conditions & MeSH terms

• Endocarditis
• Obesity

Intervention

Other:
• Endocarditis
Comparison : Endocarditis vs. control
• Obese vs. control
Comparisons : Obese vs. control

Locations

Country	Name	City	State
France	Chu Clermont-Ferrand	Clermont-Ferrand

Sponsors (5)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand	Auvergne/Rhône-Alpes area, Heart and Research Foundation, Institut National de la Recherche Agronomique, University of Clermont-Auvergne

Country where clinical trial is conducted

France, 

References & Publications (1)

Mourmoura E, Rigaudière JP, Couturier K, Hininger I, Laillet B, Malpuech-Brugère C, Azarnoush K, Demaison L. Long-term abdominal adiposity activates several parameters of cardiac energy function. J Physiol Biochem. 2016 Sep;72(3):525-37. doi: 10.1007/s13105-015-0427-7. Epub 2015 Aug 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mitochondrial function	Measurement of oxidative phosphorylation and reactive oxygen species release in isolated human cardiac mitochondria	at day 1 (Moment of the surgery)
Secondary	walk test	6-minutes walk test	at the moment of inclusion in the study (day (-10-5)) and of the end of hospitalization (day +7+10)
Secondary	body composition	determination of lean masses by impedance-metry	1 day before the surgery
Secondary	Electrocardiogram : Detections of the rates in events per min of arrhythmias	Detections of the rates in events per min of arrhythmias (existence of P wave followed by a QRS complex) and atrio-ventricular blocks in all the patients	at days (-10-5), (+7+10), (+30) and (+90)
Secondary	Membrane lipid composition	Fatty acid composition of plasma lipids	at day 1 (at the day of surgery)
Secondary	Markers of oxidative stress in the plasma	Markers of the oxidative stress in the plasma (amounts of thiol groups and TBARS, activities of SOD, catalase, glutathione peroxidase, ratio between the amounts of GSH and GSSG) and in the myocardium (whole myocardium: ratio between the activities of aconitase and fumarase, amount of protein carbonylation; isolated mitochondria: amount of nitrosylated proteins)	at days (0) and (+30) for the plasma and day (0) for the myocardium
Secondary	Concentrations of inflammation cytokines in the plasma	Inflammatory cytokines in the plasma (IL-6, IL-1b, TNF-a, fibrinogen, CRP and pro-calcitonin	at days (-10-5), (0), (+1), (+2), (+7) and (+90)
Secondary	Semi-quantitative analysis of the amounts of approximatively 6000 molecules in the plasma by metabolomic and lipidomic techniques	Studies performed in the plasma by a U.S. private society (Metabolon)	at days (0) and (+30)
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Exercise testing	at day (+30)
Secondary	Patient follow-up during the hospital stay	quantity of time (h) spent by the patient during the stay in reanimation	morbi-mortality at day (+90)
Secondary	Morbi-mortality	rates of deaths and complications (cardiac, renal, hepatic, etc.) during the 90 days following the surgery for all the patients	measurement during the post-operative 90 days