Severe Obesity Clinical Trial
— OBESICAOfficial title:
Interest of a Diet Rich in Cajanus Cajan (Pigeon Pea) Associated With a Standardized Exercise Protocol on NLRP3 Inflammasome Expression and Weight Loss in Adult Patients With Severe Obesity.
Adult obesity is due to an excess of body fat. This corresponds to all the fat in the body (or adipose tissue). It is opposed to the lean mass which corresponds to the weight of muscles, organs and viscera. It is defined from the body mass index (or BMI). BMI is calculated by dividing a person's weight by their height squared. According to these criteria, the prevalence of obesity has reached 17% of the entire adult population in mainland France (ESTENBAN 2015 study). The prevalence figures for obesity in the French overseas departments are higher than in mainland France. The latest epidemiological data available in Martinique and Guadeloupe (KANNARI 2015 study) show that approximately 60% of the adult population is overweight and 25% of the adult population is obese. Obesity is considered a chronic disease that increases the risk of cardiovascular and metabolic complications all the more when patients have a BMI ≥ 35 kg/m2, defining severe obesity. When BMI is equal to or exceeds 40 kg/m2, obesity is said to be "morbid" and the risk of cardiovascular complications increases by about 100% to 400% depending on the type of complications. The risk of mortality increases by 50 to 100% compared to the normal weight population. Obesity and inflammation Adipose tissue accumulates around the abdominal viscera after the fat storage capacity of the subcutaneous territories has been reached. The accumulation of visceral fat is accompanied by a low-grade inflammatory response that is responsible for the secretion of lipid derivatives and mediators toxic to the cardiovascular system and insulin sensitivity. The inflammatory response is characterized by the expression of numerous pro-inflammatory molecules synthesized by adipocytes and immunocompetent single-macrophage cells infiltrating the vascular stroma of adipose tissue. In addition, hyperglycemia and excess lipid intermediates cause the assembly of inflammasomes in the cytosol. Among them, the NLRP3 inflammasome involved in multiple human inflammatory pathologies. Inflammation opposes weight loss, hence the need to reduce the inflammatory response to facilitate weight loss in obese people. Pigeon pea, known for its anti-inflammatory properties, is a legume found in Creole gardens and traditionally eaten at Christmas. The OBESICA study aims at studying the interest of consuming pigeon pea associated with regular physical activity on the inflammatory state of the body and weight loss in obese patients.
Status | Not yet recruiting |
Enrollment | 124 |
Est. completion date | September 2025 |
Est. primary completion date | November 2024 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Have a BMI = 35 kg/m² (severely obese) - Ability, at the time of inclusion, to follow a personalized physical activity program for 24 weeks. - Have agreed to follow-up for up to 36 weeks - Be affiliated to a social security system - Be able to freely give informed consent (oral) Exclusion Criteria: - Pregnant woman - Have a history of type 1 diabetes - Weight >150 kg (criterion related to the capacity of the exercise bikes used in the study) - History of renal disease [glomerular filtration < 30 mL/min], cardiovascular history of myocardial ischemia (ECG signs), uncontrolled hypertension [at rest; systolic blood pressure > 140 mm Hg and diastolic blood pressure > 90 mm Hg], heart failure, cardiac valvulopathy, peripheral arterial disease or arteritis, and stroke. - Have an auto-inflammatory or autoimmune pathology known to modify the expression of NLRP3 (cryopyrinopathies, Crohn's disease, gouty arthritis, chondrocalcinosis, arthritic diseases, type 1 diabetes, Biermer's disease, Basedow's disease, rheumatoid arthritis, systemic lupus erythematosus, sclerodermias, non-alcoholic liver steatosis, multiple sclerosis, Alzheimer's and Parkinson's diseases) - Have a history of recent (<6 months) infectious disease of viral, parasitic, fungal or bacterial origin known to modify the expression of NLRP3 - Taking medication that may affect weight gain (systemic corticosteroids, psychotropic drugs, migraine medications, beta-blockers, chemotherapy, and antibiotics) - Have completed a personalized physical activity program in the 12 weeks prior to inclusion, - Have bariatric surgery scheduled within 6 months of inclusion, - Have a known intolerance to legume seeds - Have an unbalanced low-calorie diet - Have consumed dietary supplements containing polyphenols of the flavonoid class (green tea catechins and isoflavones from soy and legume seeds in the 3 months prior to inclusion). |
Country | Name | City | State |
---|---|---|---|
Martinique | CHU de Martinique | Fort-de-France |
Lead Sponsor | Collaborator |
---|---|
University Hospital Center of Martinique | GIRCI SOHO |
Martinique,
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Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Assessment of NLRP3 expression | Basal level variation in mRNA expression of the NLRP3 gene (coding for the NLRP3 protein subunit of the NLRP3 inflammasome), in monocytes isolated from peripheral blood. This variation will be measured by RT-qPCR (Quantitative reverse transcription PCR) and will be expressed in DNA copy number (absolute quantification) using a standard range performed with known quantities of complementary DNA, copies of the RNA of interest. | Randomization, 6 and 9 months +/- 8 days post randomisation | |
Secondary | mRNA expression of caspase-1 | The inflammasome NLRP3 is a multi-protein platform (NLRP3, ASC, pro caspase-1) with an active assembly of inflammatory caspases (notably caspase-1) that cleaves the pro-interleukins IL-1ß and IL-18 into mature pro-inflammatory cytokines.
The biological evaluation criteria will be the mRNA expression of caspase-1 gene in monocytes isolated from peripheral blood measured in cDNA copy number. |
Randomization, 6 and 9 months +/- 8 days post randomisation | |
Secondary | mRNA expression of AUC | The inflammasome NLRP3 is a multi-protein platform (NLRP3, ASC, pro caspase-1) with an active assembly of inflammatory caspases (notably caspase-1) that cleaves the pro-interleukins IL-1ß and IL-18 into mature pro-inflammatory cytokines.
The biological evaluation criteria will be the mRNA expression of AUC (apoptotic speck protein containing a caspase recruitment domain) gene in monocytes isolated from peripheral blood measured in cDNA copy number. |
Randomization, 6 and 9 months +/- 8 days post randomisation | |
Secondary | mRNA expression of IL-1ß | The inflammasome NLRP3 is a multi-protein platform (NLRP3, ASC, pro caspase-1) with an active assembly of inflammatory caspases (notably caspase-1) that cleaves the pro-interleukins IL-1ß and IL-18 into mature pro-inflammatory cytokines.
The biological evaluation criteria will be the mRNA expression of IL-1ß in monocytes isolated from peripheral blood measured in copy number. |
Randomization, 6 and 9 months +/- 8 days post randomisation | |
Secondary | mRNA expression of IL18 | The inflammasome NLRP3 is a multi-protein platform (NLRP3, ASC, pro caspase-1) with an active assembly of inflammatory caspases (notably caspase-1) that cleaves the pro-interleukins IL-1ß and IL-18 into mature pro-inflammatory cytokines.
The biological evaluation criteria will be the mRNA expression of IL18 in monocytes isolated from peripheral blood measured in copy number. |
Randomization, 6 and 9 months +/- 8 days post randomisation | |
Secondary | Plasma level of the pro-inflammatory cytokines IL-1ß | The inflammasome NLRP3 is a multi-protein platform (NLRP3, ASC, pro caspase-1) with an active assembly of inflammatory caspases (notably caspase-1) that cleaves the pro-interleukins IL-1ß and IL-18 into mature pro-inflammatory cytokines.
The biological evaluation criteria will be the plasma level of the pro-inflammatory cytokines IL-1ß measured by ELISA kits in pg/mL. |
Randomization, 6 and 9 months +/- 8 days post randomisation | |
Secondary | Plasma level of the pro-inflammatory cytokines IL18 | The inflammasome NLRP3 is a multi-protein platform (NLRP3, ASC, pro caspase-1) with an active assembly of inflammatory caspases (notably caspase-1) that cleaves the pro-interleukins IL-1ß and IL-18 into mature pro-inflammatory cytokines.
The biological evaluation criteria will be the plasma level of the pro-inflammatory cytokines IL18 measured by ELISA kits in pg/mL. |
Randomization, 6 and 9 months +/- 8 days post randomisation | |
Secondary | Plasma level of ultra-sensitive C-reactive Protein | The biological evaluation criteria will be the plasma level of ultra-sensitive C-reactive Protein measured in mg/mL. | Randomization, 6 and 9 months +/- 8 days post randomisation | |
Secondary | Weight loss assessment | Weight measurement in kg | Randomization, 6 and 9 months +/- 8 days post randomisation | |
Secondary | Body mass index assessment | Body mass index measurement | Randomization, 6 and 9 months +/- 8 days post randomisation | |
Secondary | Abdominal perimeter assessment | Abdominal perimeter measurement in centimeters | Randomization, 6 and 9 months +/- 8 days post randomisation | |
Secondary | Hip circumference assessment | Hip circumference measurement in in centimeters | Randomization, 6 and 9 months +/- 8 days post randomisation | |
Secondary | Body composition assessment | Body composition by impedance meter (%) | Randomization, 6 and 9 months +/- 8 days post randomisation |
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