Metagenomics and Integrative Systems Medicine of Cardiometabolic Diseases
- Conditions
- Cardiometabolic Disease
- Interventions
- Other: Adipose tissue biopsies (omental and subcutaneous) liverRadiation: CT-scanOther: Stools samplingOther: DNA samplingOther: Blood samplingOther: Urine samplingRadiation: Dual energy X-ray absorptiometry-scan (DEXA-scan)
- Registration Number
- NCT02059538
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
Supported by state-of-the-art systems medicine competences including integrative computational and functional genomics, the overarching goal of the trial is to investigate the impact of qualitative and quantitative changes in the gut microbiota on the pathogenesis of cardiometabolic diseases (CMDs) and their associated co-morbidities. A major objective will be to translate the clinical and fundamental based discoveries into new diagnosis and preventive actions paving the way to novel modes of treatment in the successive stages of CMD progression.
- Detailed Description
Cardiovascular diseases represent a huge medico-economic issue that is supported by public health policy. It is linked not only to the high prevalence of these diseases but also the associated cost they encounter for. Therefore, it seems rather urgent to create and validate tools to predict evolution of this group of disease in order to better take care of patients before they enter the more chronic stages which induce increased costs and socioeconomic and medical burdens.
It is now well acknowledged that gut microbiota is modified in some metabolic disease such as type-2 diabetes but also in inflammatory diseases. However, gut microbiota is still insufficiently explored in cardiovascular disease, although it could represent a useful, non-invasive and practical tool in the daily care of patients.
Investigators aim to deepen the knowledge and characterization of gut microbiota in patients going from metabolic diseases such as metabolic syndrome, obesity and type 2 diabetes (which are risks factors for cardiovascular diseases) to overt coronary artery diseases (from the first event to end stage heart failure). Investigators will use a system medicine approach whose aim is to integrate numerous data coming from different technologies (including environment, transcriptomics, metabolomics, metagenomics, lipidomics and bioinformatics). These integrated approaches are needed to translate basic science findings into clinical practice for the benefit of the patients.
Investigators aim to uncover new microbial signatures that could help diagnose and/or predict both the natural evolution of cardiometabolic diseases and the response to treatment. Investigators aim to go forward personalized medicine.
Patients will be approached for enrolment during their hospitalization in the 3 centers during the 24-month enrolment phase (WP3). Once the informed consent completed, each patient will be assessed for CMD phenotypes including clinical examination, environmental and food habit evaluation, blood urine and feces samples. In each group of patients, a sub-sample of 30 to 50 subjects will be included in one or more advanced phenotyping items. This will include whole body composition by absorptiometry (DXA), abdominal visceral fat by tomodensitometry, Oral Glucose Tolerance Test (OGTT) (glucose, insulin, incretins), subcutaneous fat biopsy, cardiac echocardiography, intima media thickness, pulse wave velocity. For the obese patients undergoing bariatric surgery: liver and subcutaneous and omental adipose tissue biopsies will be obtained during surgery.
This group of patient will be followed at 3, 6 and 12 months after their surgery and will have the same examination as mentioned above.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 2350
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 5 DNA sampling Patients with stable chronic coronary artery disease without heart failure Group 3 Urine sampling Type-2 diabetics patients Group 3 Dual energy X-ray absorptiometry-scan (DEXA-scan) Type-2 diabetics patients Group 6 CT-scan Patients with ischemic systolic heart failure (CHF) Group 8 Urine sampling Healthy volunteers Group 8 Dual energy X-ray absorptiometry-scan (DEXA-scan) Healthy volunteers Group 4 Urine sampling Patients with first recent (\< 2 weeks) acute coronary syndrome (ACS) Group 7 Urine sampling Patients with non-ischemic chronic heart failure Group 1 Adipose tissue biopsies (omental and subcutaneous) liver Metabolic syndrome Group 1 Dual energy X-ray absorptiometry-scan (DEXA-scan) Metabolic syndrome Group 2 CT-scan Severly obese patients Group 5 Urine sampling Patients with stable chronic coronary artery disease without heart failure Group 5 Dual energy X-ray absorptiometry-scan (DEXA-scan) Patients with stable chronic coronary artery disease without heart failure Group 2 Dual energy X-ray absorptiometry-scan (DEXA-scan) Severly obese patients Group 3 Stools sampling Type-2 diabetics patients Group 1 CT-scan Metabolic syndrome Group 1 Urine sampling Metabolic syndrome Group 3 Adipose tissue biopsies (omental and subcutaneous) liver Type-2 diabetics patients Group 4 Adipose tissue biopsies (omental and subcutaneous) liver Patients with first recent (\< 2 weeks) acute coronary syndrome (ACS) Group 4 DNA sampling Patients with first recent (\< 2 weeks) acute coronary syndrome (ACS) Group 5 Adipose tissue biopsies (omental and subcutaneous) liver Patients with stable chronic coronary artery disease without heart failure Group 5 Stools sampling Patients with stable chronic coronary artery disease without heart failure Group 7 Stools sampling Patients with non-ischemic chronic heart failure Group 8 DNA sampling Healthy volunteers Group 2 Adipose tissue biopsies (omental and subcutaneous) liver Severly obese patients Group 2 DNA sampling Severly obese patients Group 3 Blood sampling Type-2 diabetics patients Group 4 Blood sampling Patients with first recent (\< 2 weeks) acute coronary syndrome (ACS) Group 1 Stools sampling Metabolic syndrome Group 1 Blood sampling Metabolic syndrome Group 2 Stools sampling Severly obese patients Group 2 Urine sampling Severly obese patients Group 3 CT-scan Type-2 diabetics patients Group 4 Stools sampling Patients with first recent (\< 2 weeks) acute coronary syndrome (ACS) Group 1 DNA sampling Metabolic syndrome Group 2 Blood sampling Severly obese patients Group 3 DNA sampling Type-2 diabetics patients Group 4 CT-scan Patients with first recent (\< 2 weeks) acute coronary syndrome (ACS) Group 6 Stools sampling Patients with ischemic systolic heart failure (CHF) Group 6 Blood sampling Patients with ischemic systolic heart failure (CHF) Group 5 CT-scan Patients with stable chronic coronary artery disease without heart failure Group 5 Blood sampling Patients with stable chronic coronary artery disease without heart failure Group 4 Dual energy X-ray absorptiometry-scan (DEXA-scan) Patients with first recent (\< 2 weeks) acute coronary syndrome (ACS) Group 6 Adipose tissue biopsies (omental and subcutaneous) liver Patients with ischemic systolic heart failure (CHF) Group 6 DNA sampling Patients with ischemic systolic heart failure (CHF) Group 7 Adipose tissue biopsies (omental and subcutaneous) liver Patients with non-ischemic chronic heart failure Group 7 Dual energy X-ray absorptiometry-scan (DEXA-scan) Patients with non-ischemic chronic heart failure Group 8 Blood sampling Healthy volunteers Group 6 Dual energy X-ray absorptiometry-scan (DEXA-scan) Patients with ischemic systolic heart failure (CHF) Group 7 CT-scan Patients with non-ischemic chronic heart failure Group 7 DNA sampling Patients with non-ischemic chronic heart failure Group 7 Blood sampling Patients with non-ischemic chronic heart failure Group 6 Urine sampling Patients with ischemic systolic heart failure (CHF) Group 8 Stools sampling Healthy volunteers
- Primary Outcome Measures
Name Time Method Look for differences in gut microbiota signatures using metagenomic approach in the 8 different groups baseline Look for differences in gut microbiota signatures using metagenomic approach in the 8 different groups (metabolic syndrome, type 2 diabetes, obesity, acute coronary event, chronic coronaropathy with or without cardiac insufficiency, cardiac insufficiency without coronaropathy and controls), in order to uncover gut derived signature associated with CMD stages
- Secondary Outcome Measures
Name Time Method Establish differences in fecal metabolomic signatures using 1H nuclear magnetic resonance (NMR) spectroscopy and Ultra-high Performance Liquid Chromatography Mass Spectrometry ((UPLC-MS) on fecal samples) in the 8 different groups (cf above mentioned) baseline
Trial Locations
- Locations (3)
University of Copenhagen
🇩🇰Copenhagen, Denmark
University of Leipzig
🇩🇪Leipzig, Germany
Hôpital Pitié-Salpétrière
🇫🇷Paris, France