Study of the Role of PCSK9 and FXR in the Physiopathology of the Joint Dyslipidemia Associated to the Human Immunoresistance

Experimental results are strongly suggesting that PCSK9 and FXR could occur in the physiopathology of human joined dyslipidemia. But no data in the literature can validate the potential role of these two genes in the lipidic and glucidic metabolism control in physiopathological situations. This protocol is based on the hypothesis that the expression levels of PCSK 9 and FXR are modified for some patients suffering from insulin resistance and dyslipidemia.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Procedure: biopsy of muscle, of liver, and of adipose tissue; Procedure: clamp euglycemic - hyperglycemic; Behavioral: diet; Other: biopsies for biological and genetic analyses

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • CHU de Nantes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• corporal mass index > 40 kg/m² or > 35 kg/m² associated to a co-morbidity resistant to a diet
• bariatric surgery planned
• no lipid-lowering drugs during 4 weeks before surgery
• no treatment by metformin during 4 weeks before surgery
• no treatment by glitazones during 8 weeks before surgery
• age of the patient between 18 and 65 years
• consent form signed
• patient with social insurance

Exclusion Criteria:

• age inferior to 18 years
• women pregnant
• coagulation troubles
• surgery contraindicated
• Chronic hepatitis B or C active
• VIH infected
• other chronic hepatic disease
• patient with dyslipidemia under lipid-lowering drugs in secondary prevention of a cardiovascular pathology
• Type 2 diabetes under insulinosensitivator treatments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Non diabetic non dyslipidemic patient	Procedure: biopsy of muscle, of liver, and of adipose tissue; biopsy of muscle, of liver, and of adipose tissue; Procedure: clamp euglycemic - hyperglycemic; clamp euglycemic-hyperglycemic; Behavioral: diet; diet; Other: biopsies for biological and genetic analyses; biopsies for biological and genetic analyses
Experimental: 2; Patient with metabolic syndrome	Procedure: biopsy of muscle, of liver, and of adipose tissue; biopsy of muscle, of liver, and of adipose tissue; Procedure: clamp euglycemic - hyperglycemic; clamp euglycemic-hyperglycemic; Behavioral: diet; diet; Other: biopsies for biological and genetic analyses; biopsies for biological and genetic analyses
Experimental: 3; Patients with type II diabetes	Procedure: biopsy of muscle, of liver, and of adipose tissue; biopsy of muscle, of liver, and of adipose tissue; Procedure: clamp euglycemic - hyperglycemic; clamp euglycemic-hyperglycemic; Behavioral: diet; diet; Other: biopsies for biological and genetic analyses; biopsies for biological and genetic analyses
Experimental: 4; Patient with a single lipidic anomaly	Procedure: biopsy of muscle, of liver, and of adipose tissue; biopsy of muscle, of liver, and of adipose tissue; Procedure: clamp euglycemic - hyperglycemic; clamp euglycemic-hyperglycemic; Behavioral: diet; diet; Other: biopsies for biological and genetic analyses; biopsies for biological and genetic analyses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the relationship between the expression levels of PCSK9 and FXR in the liver, adipose tissue and muscle and the different components of the insulin resistance syndrome obese patients submitted to bariatric surgery	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Relationship between the levels of hepatic expression of PCSK9 and FXR and the degree of NASH in these patients. - Search for mutations and polymorphisms in the gene PCSK9 and FXR and their promoter regions	2 years

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Bertrand Cariou, MD, CHU de Nantes; Principal Investigator: Michel Krempf, MD, CHU de Nantes; Principal Investigator: Yassine Zaïr, MD, CHU de Nantes; Principal Investigator: Eric Letessier, MD, CHU de Nantes; Principal Investigator: Charles Couet, MD, Chu De Tours; Principal Investigator: Noël Huten, MD, Chu De Tours; Principal Investigator: Philippe Topart, MD, CHU de Brest; Principal Investigator: David Lechaux, MD, CHU de St Brieuc; Principal Investigator: Jean-Pierre Faure, MD, Poitiers University Hospital

Publications and helpful links

General Publications

• Blanchard C, Ledoux S, Verhaegen A, Wargny M, Letessier E, Stepanian A, Huten N, Jacobi D, Krempf M, Le Bras M, Perrocheau Guillouche M, Arnaud L, Pichelin M, Van Gaal L, Cariou B, Le May C. Roux-en-Y gastric bypass, but not sleeve gastrectomy, decreases plasma PCSK9 levels in morbidly obese patients. Diabetes Metab. 2020 Nov;46(6):480-487. doi: 10.1016/j.diabet.2020.01.003. Epub 2020 Feb 4.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: January 12, 2007
• First Submitted That Met QC Criteria: January 12, 2007
• First Posted (Estimate): January 15, 2007

Study Record Updates

• Last Update Posted (Estimate): April 3, 2014
• Last Update Submitted That Met QC Criteria: April 2, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: bariatric surgery planned
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias
• Other Study ID Numbers: BRD 06/8-I; ID RCB 2006-A00196-45; DGS2006-0090