Inflammation Regulation in Obese Patients

Obesity Clinical Trial

Official title:

Relations Between Obesity and Insulin Resistance: Role of Inflammation Regulatory Mechanisms in Obese Patients Without Associated Comorbidity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01561664
• Other study ID #: 8685
• Status: Completed
• Phase: N/A
• First received: March 6, 2012
• Last updated: September 17, 2015
• Start date: November 2011
• Est. completion date: December 2013

Study information

• Verified date: March 2012
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

Insulin resistance is one of the main mechanisms involved in metabolic diseases. inflammation has been implicated in its pathogenesis, due to innate immunity activation by free fatty acids, lipopolysaccharides (LPS) and lactate. Free fatty acids, LPS and lactate activate innate immunity in squelettal muscle and adipose tissue via Toll-like receptor 2/4, NFkB, IRF3 (Interferon Responsive Factor 3) and cytokines secretion (TNFa, IFN g, IL1b, IL6), chemokines secretion (MCP1) and leukotrienes (LTB4). Feed back mechanisms involved in TLR signaling pathways as RLI (ribonuclease L inhibitor)/ABCE1, have never been studied in inflammation due to obesity. RLI inhibits an endoribonuclease, RNase L, which has been recently implicated in TLR signaling The purpose of this study is to analyse the role of RLI and RNase L in TLR regulation, and its potential implication in the link between obesity, inflammation and insulin resistance in adipose tissue and squeletal muscle in humans.

Description:

The investigators working hypothesis is that RNase L and RLI contribute to chronic inflammation regulation and to insulin response through TLR 4 pathway regulation in obesity. The investigators main purpose is to compare innate immunity activation pathway between insulin sensitive, insulin resistant obese patients and control patients. Insulin sensitive and insulin resistant obese patients will be distinguish thanks to the HOMA ir index. The investigators second objectives are to evaluate if the degree of inflammation in adipose tissue and squeletal muscle is correlated to insulin sensitivity measured by hyperinsulinemic euglycemic clamp and to characterise inflammatory pathway and regulation pathway. A special focus will be given to the leukotrienes and their potential role in insulin resistance pathogenesis. The investigators will have two approaches:- characterisation of subjects with normal weight, of obese insulin sensitive and obese insulin resistant through a metabolic evaluation, an inflammatory characterisation and a measure of insulin sensitivity at the systemic level, in adipose tissue and in squeletal muscle.- an in vitron approach with human myoblast and adipocytes culture, extracted from the investigators patients: characterisation of inflammation, innate immunity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2013
• Est. primary completion date: November 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 50 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age between 50 and 65 years old

• Men/ menopausal women

• BMI <25 kg/m2 for the control group, BMI >30 kg/m2 for the obese group

• Non diabetic patients

• HOMAIR <3 for the insulin sensitive obese group

• Non smoking

• Without any inflammatory disease

• Without any first degrees relative with diabetes

• Without any treatment that could interfere with insulin sensitivity

• without any infection

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Insulin Resistance
• Obesity

Intervention

Other:
• muscle and fat biopsy
muscle and fat biopsy

Locations

Country	Name	City	State
France	Montpellier University Hospital	Montpellier

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TLR regulation	analyse the role of RLI and RNase L in TLR regulation, and its potential implication in the link between obesity, microinflammation and insulin resistance in adipose tissue and squelettal muscle in humans.	2 years	No