Obesity MorbidBARIAMITRINCT04814147
Role NLRP3 Inflammasome in Weight Loss Following Sleeve Gastrectomy in Morbidly Obese Patients
An observational study of Obesity Morbid and Obesity-Associated Insulin Resistance, run by University Hospital Center of Martinique at 1 site in Martinique.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Obesity Morbid, Obesity-Associated Insulin Resistance
- What is being tested?
- Sleeve gastrectomy
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 20 participants
- Where
- 1 siteMartinique
- Study dates
- 13 Mar 2021to 12 Jun 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Study population: Due to the almost exclusive type of recruitment of obese women by the obesity management centre of CHU Martinique (around 90% of patients), only obese women aged between 18 and 45 years old will be included in the study. Only patients who have undergone a sleeve gastrectomy will be included in the study, as this surgical procedure is performed on approximately 9 out of 10 patients in the digestive surgery department of the CHU de Martinique.
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Martinique1 site, 1 recruiting
- Recruiting
CHU de Martinique
Fort-de-France, 97261
Emmanuel RIVKINE, MD, +596596552311, emmanuel.rivkine@chu-martinique.fr
Emmanuel RIVKINE, MD
About this study
Official title: Role of NLRP3 Inflammasome Activation of Adipose Tissue in the Progression of Weight Loss After Sleeve Gastrectomy in Morbidly Obese Patients.
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.
Read more
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.
Read the detailed 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 IL1β and IL18 into mature pro-inflammatory cytokines IL1β 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.
- Being tested
- Sleeve gastrectomy
- Keywords
- Obesity, cardiovascular risk, diabetes
- Medical subject headings
- Obesity, Morbid, Obesity, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sleeve gastrectomyProcedure or surgery
Measure of NLRP3 inflammasome preoperative activation level by the expression of NLRP3, IL-1β, IL18 and caspase-1 mRNAs in subcutaneous and visceral adipose tissue. of the epiploon;
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight loss (kg) at 12 months of sleeve gastrectomy
Magnitude of weight loss (kg) at 12 months of sleeve gastrectomy as a function of the level of preoperative activation of the NLRP3 inflammasome.
Measured: 12 months
Secondary outcomes (6)
Preoperative activation level of the NLRP3 inflammasome
Preoperative activation level of the NLRP3 inflammasome will be measured by the expression of NLRP3, IL-1β, IL18 and caspase-1 mRNAs in subcutaneous and visceral adipose tissue of the epiploon; expressed as mRNA copy number measured in quantitative RT-PCR (RT-qPCR)
Measured: 1 day
Mitochondrial activity
Preoperative levels of oxygen consumption by the mitochondrial respiratory chain (pmol O2*s-1*mg-1 of dry tissue)
Measured: 1 day
Pre and post operative inflammatory state
Pre- and post-operative plasma levels of CRP and proinflammatory cytokines IL-1β and IL18 (pg/mL). Postoperative measurements will be done up to 6 months after bariatric surgery. In addition, since fat tissue sampling is not justified postoperatively, activation of the NLRP3 inflammasome will be assessed indirectly by plasma concentrations of the cytokines IL-1β and IL18
Measured: 24 months
Pre and post-operative BMI
Weight and height will be combined to report BMI in kg/m^2) at pre- and post-operative
Measured: 24 months
Pre and post-operative abdominal perimeter
Abdominal perimeter in centimeter at pre- and post-operative (24-month follow-up).
Measured: 24 months
Pre and post-operative hip circumference
Hip circumference in centimeter at pre- and post-operative (24-month follow-up).
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2021
- Study start13 Mar 2021
- Primary completion13 Jun 2024 (estimated)
- Study completion12 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Obesity MorbidStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Center of Martinique
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rémi NEVIERE, MD, PhD, Study chair, CHU de MartiniqueEmmanuel RIVKINE, Principal investigator, CHU de Martinique
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04814147
- Sponsor's protocol ID
- 18_RIPH3-14
- Acronym
- BARIAMITRI
- Status last verified
- Aug 2023
- First submitted
- 24 Nov 2020
- Last updated
- 28 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Neeland IJ, Poirier P, Despres JP. Cardiovascular and Metabolic Heterogeneity of Obesity: Clinical Challenges and Implications for Management. Circulation. 2018 Mar 27;137(13):1391-1406. doi: 10.1161/CIRCULATIONAHA.117.029617.
PubMed 29581366Vecchie A, Dallegri F, Carbone F, Bonaventura A, Liberale L, Portincasa P, Fruhbeck G, Montecucco F. Obesity phenotypes and their paradoxical association with cardiovascular diseases. Eur J Intern Med. 2018 Feb;48:6-17. doi: 10.1016/j.ejim.2017.10.020.
PubMed 29100895le Roux CW, Heneghan HM. Bariatric Surgery for Obesity. Med Clin North Am. 2018 Jan;102(1):165-182. doi: 10.1016/j.mcna.2017.08.011.
PubMed 29156184Pareek M, Schauer PR, Kaplan LM, Leiter LA, Rubino F, Bhatt DL. Metabolic Surgery: Weight Loss, Diabetes, and Beyond. J Am Coll Cardiol. 2018 Feb 13;71(6):670-687. doi: 10.1016/j.jacc.2017.12.014.
PubMed 29420964Lupoli R, Lembo E, Saldalamacchia G, Avola CK, Angrisani L, Capaldo B. Bariatric surgery and long-term nutritional issues. World J Diabetes. 2017 Nov 15;8(11):464-474. doi: 10.4239/wjd.v8.i11.464.
PubMed 29204255
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of NLRP3 Inflammasome Activation of Adipose Tissue in the Progression of Weight Loss After Sleeve Gastrectomy in Morbidly Obese Patients.
- ClinicalTrials.gov ID
- NCT04814147
- Acronym / sponsor ID
- BARIAMITRI / 18_RIPH3-14
- Keywords
- Obesity, cardiovascular risk, diabetes
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Hospital Center of MartiniqueUniversity, hospital or other
- Study start
- 13 Mar 2021 (actual)
- Primary completion
- 13 Jun 2024 (estimated)
- Study completion
- 12 Jun 2025 (estimated)
- First posted
- 24 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 IL1β and IL18 into mature pro-inflammatory cytokines IL1β 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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Due to the almost exclusive type of recruitment of obese women by the obesity management centre of CHU Martinique (around 90% of patients), only obese women aged between 18 and 45 years old will be included in the study. Only patients who have undergone a sleeve gastrectomy will be included in the study, as this surgical procedure is performed on approximately 9 out of 10 patients in the digestive surgery department of the CHU de Martinique.
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sleeve gastrectomyMeasure of NLRP3 inflammasome preoperative activation level by the expression of NLRP3, IL-1β, IL18 and caspase-1 mRNAs in subcutaneous and visceral adipose tissue. of the epiploon; | Procedure or surgery | – |
Primary outcome
Weight loss (kg) at 12 months of sleeve gastrectomy
Time frame: 12 months
Magnitude of weight loss (kg) at 12 months of sleeve gastrectomy as a function of the level of preoperative activation of the NLRP3 inflammasome.
6 secondary outcomes
Preoperative activation level of the NLRP3 inflammasome
Time frame: 1 day
Mitochondrial activity
Time frame: 1 day
Pre and post operative inflammatory state
Time frame: 24 months
Pre and post-operative BMI
Time frame: 24 months
Pre and post-operative abdominal perimeter
Time frame: 24 months
Pre and post-operative hip circumference
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2023.
- Results publication: PubMed 29581366Neeland IJ, Poirier P, Despres JP. Cardiovascular and Metabolic Heterogeneity of Obesity: Clinical Challenges and Implications for Management. Circulation. 2018 Mar 27;137(13):1391-1406. doi: 10.1161/CIRCULATIONAHA.117.029617.
- Results publication: PubMed 29100895Vecchie A, Dallegri F, Carbone F, Bonaventura A, Liberale L, Portincasa P, Fruhbeck G, Montecucco F. Obesity phenotypes and their paradoxical association with cardiovascular diseases. Eur J Intern Med. 2018 Feb;48:6-17. doi: 10.1016/j.ejim.2017.10.020.
- Results publication: PubMed 29156184le Roux CW, Heneghan HM. Bariatric Surgery for Obesity. Med Clin North Am. 2018 Jan;102(1):165-182. doi: 10.1016/j.mcna.2017.08.011.
- Results publication: PubMed 29420964Pareek M, Schauer PR, Kaplan LM, Leiter LA, Rubino F, Bhatt DL. Metabolic Surgery: Weight Loss, Diabetes, and Beyond. J Am Coll Cardiol. 2018 Feb 13;71(6):670-687. doi: 10.1016/j.jacc.2017.12.014.
- Results publication: PubMed 29204255Lupoli R, Lembo E, Saldalamacchia G, Avola CK, Angrisani L, Capaldo B. Bariatric surgery and long-term nutritional issues. World J Diabetes. 2017 Nov 15;8(11):464-474. doi: 10.4239/wjd.v8.i11.464.
- WHO : obesity and overweightLink provided by the sponsor.
- Overweight and abdominal obesity (KANNARI study in Martinique)Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rémi NEVIERE, MD, PhD study chair
CHU de Martinique
Emmanuel RIVKINE principal investigator
CHU de Martinique
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Obesity Morbid and Obesity-Associated Insulin Resistance, run by University Hospital Center of Martinique at 1 site in Martinique.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Martinique. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jocelyne CRASPAG, MSc (+596596592698, jocelyne.craspag@chu-martinique.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weight loss (kg) at 12 months of sleeve gastrectomy (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04814147, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2023.