Clinical trial NCT00422006: Study of the Role of PCSK9 and FXR in the Physiopathology of the Joint Dyslipidemia Associated to the Human Immunoresistance
Official title: Study of the Role of PCSK9 and FXR in the Physiopathology of the Joint Dyslipidemia Associated to the Human Immunoresistance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Keywords: bariatric surgery planned
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2007-01-15
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 2 years
Secondary outcomes:
measure: 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
timeFrame: 2 years
Other outcomes:
Locations:
city: Nantes
country: France
facility: CHU de Nantes
Study officials:
affiliation: Nantes University Hospital
name: Bertrand Cariou, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nantes University Hospital
name: Michel Krempf, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nantes University Hospital
name: Yassine Zaïr, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nantes University Hospital
name: Eric Letessier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Tours
name: Charles Couet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Tours
name: Noël Huten, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Brest
name: Philippe Topart, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de St Brieuc
name: David Lechaux, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Poitiers University Hospital
name: Jean-Pierre Faure, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.