Role NLRP3 Inflammasome in Weight Loss Following Sleeve Gastrectomy in Morbidly Obese Patients

  • STATUS
    Recruiting
  • End date
    Dec 30, 2023
  • participants needed
    20
  • sponsor
    University Hospital Center of Martinique
Updated on 3 April 2021

Summary

Epidemiological studies show a very rapid increase in the epidemic of obesity in the Caribbean population. 6 out of 10 adults are overweight and 1 out of 4 is obese. Most are women.

Consequences : harm to health and possible reduction in life expectancy due to the association with many cardiovascular comorbidities.

Adverse effects of obesity on the cardiovascular and endocrine systems are attributed a chronic low-grade inflammatory state in obese patients. Visceral adipose tissue is largely responsible for the inflammatory syndrome. Obesity can also induce the formation of multi-protein platforms called inflammasomes also activated by mitochondrial production.

Morbid obesity treatment with sleeve gastrectomy is an effective long term therapeutic for weight loss but also beneficial in terms of insulin resistance and cardiovascular complications.

Some patients nevertheless remain resistant to the beneficial cardio-metabolic effects of bariatric surgery.

However, the mechanisms that regulate the extent of weight loss and its stabilization after bariatric surgery are still poorly understood.

Our study aims to describe the evolution of postoperative weight loss and the place of preoperative inflammation in its amplitude.

The hypothesis is that the level of inflammation in visceral fat before surgery determines the extent of postoperative weight loss in obese women who have undergone sleeve gastrectomy.

Description

Epidemiological studies show a very rapid increase in the epidemic of obesity in the Caribbean population. The latest prevalence data in Martinique show that 6 out of 10 adults are overweight and 1 out of 4 is obese (Body Mass Index, BMI 30 kg/m2). Obesity with a BMI 35 kg/m2 is said to be "morbid" because of its association with numerous cardiovascular comorbidities. A balanced diet and physical activity are effective behavioural modalities for weight loss, which, even at low intensity, can reduce cardiovascular complications and the risk of death. However, many patients do not adhere to these constraints over a long period of time and about 50% of them regain weight after the first year. These observations highlight the value of alternative therapies with lasting effects on weight loss and the cardio-metabolic comorbidities of obesity.

Bariatric surgery with vertical calibrated vertical gastroplasty with gastric resection (or sleeve gastrectomy) and Roux-en-Y gastric bypass are therapeutic options that are not only effective in the long term for weight loss but also beneficial in terms of insulin resistance and cardiovascular complications. Bariatric surgery is currently indicated for the treatment of morbid obesity with a BMI 40 kg/m2 or a BMI 35 kg/m2 in the presence of complications. Some patients nevertheless remain resistant to the beneficial cardio-metabolic effects of bariatric surgery. The reasons for this resistance are attributed to factors such as age > 60 years, female sex, BMI > 45 kg/m2, African-American or Hispanic origin, and history of type 2 diabetes. Regardless of these factors, several studies have pointed out that a chronic low-grade inflammatory state reduces the magnitude of weight loss and thus counters the beneficial cardio-metabolic effects of bariatric surgery.

Visceral adipose tissue is largely responsible for the inflammatory syndrome in obese patients, via the activation of nuclear transcription factors (NFkB, in particular) that stimulate the synthesis of numerous mediators and pro-inflammatory cytokines. Obesity can also induce the formation of multi-protein platforms called inflammasomes, including the active assembly of inflammatory caspases (caspase-1, in particular) that cleave the pro-interleukins IL1 and IL18 into mature pro-inflammatory cytokines IL1 and IL18. The role of the inflammasome NLRP3 ("NOD-like receptor family, pyrin domain containing 3") in the inflammatory response has been particularly studied in humans due to its association with multiple chronic inflammatory, infectious and cardio-metabolic pathologies. Among the biomolecules responsible for activation of the NLRP3 inflammasome during obesity are palmitate, sphingolipids and cholesterol crystals. The NLRP3 inflammasome is also activated by mitochondrial production of reactive oxygen species (ROS) and by mitochondrial DNA released from mitochondria damaged by lipo-toxicity phenomena associated with obesity. More generally, the mitochondrial dysfunction of the metabolic syndrome is considered to be the causal intracellular event of the deregulation of the inflammatory response mediated by the inflammasome.

Details
Condition Morbid obesity, severe obesity, Obesity-Associated Insulin Resistance, Obesity-Associated Insulin Resistance
Treatment sleeve gastrectomy
Clinical Study IdentifierNCT04814147
SponsorUniversity Hospital Center of Martinique
Last Modified on3 April 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Being a woman between the ages of 18 and 45
Have been well informed about bariatric surgery and perioperative risks and have benefited from a multidisciplinary evaluation by a multidisciplinary team (RCP)
Have a BMI greater than or equal to 40 kg/m2 or greater than or equal to 35 kg/m2 with at least one co-morbidity that can be improved after surgery (cardiovascular disease, sleep apnea and severe respiratory disorders, type 2 diabetes, osteoarticular diseases)
Have been informed of the research on the samples taken during care
Having stated its decision not to object to the research on the samples taken during the treatment
To have accepted medical and surgical follow-up for 24 months
Patient under the general social security system

Exclusion Criteria

Being a pregnant or nursing woman
Being a type 1 diabetic
Have inflammatory bowel disease
Have severe and unstable eating disorders
Have severe, uncontrolled cognitive, mental or psychological disorders
Have a cancerous pathology
Be addicted to alcohol and psychoactive substances (both legal and illegal)
Have a life-threatening illness in the short or medium term
Have contraindications related to surgical operations in general such as general anaesthesia
Be under legal protection measures (guardianship, curators, safeguarding of justice), and person deprived of liberty
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note