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

NCT00422006 | Completed DMC

• 3 other identifiers: BRD 06/8-IID RCB 2006-A00196-45DGS2006-0090
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity

Keywords

bariatric surgery planned

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (4)

1

EXPERIMENTAL

Non diabetic non dyslipidemic patient

Procedure: biopsy of muscle, of liver, and of adipose tissue; Procedure: clamp euglycemic - hyperglycemic; Behavioral: diet; Other: biopsies for biological and genetic analyses

2

EXPERIMENTAL

Patient with metabolic syndrome

Procedure: biopsy of muscle, of liver, and of adipose tissue; Procedure: clamp euglycemic - hyperglycemic; Behavioral: diet; Other: biopsies for biological and genetic analyses

3

EXPERIMENTAL

Patients with type II diabetes

Procedure: biopsy of muscle, of liver, and of adipose tissue; Procedure: clamp euglycemic - hyperglycemic; Behavioral: diet; Other: biopsies for biological and genetic analyses

4

EXPERIMENTAL

Patient with a single lipidic anomaly

Procedure: biopsy of muscle, of liver, and of adipose tissue; Procedure: clamp euglycemic - hyperglycemic; Behavioral: diet; Other: biopsies for biological and genetic analyses

Interventions

biopsy of muscle, of liver, and of adipose tissue PROCEDURE

biopsy of muscle, of liver, and of adipose tissue

1; 2; 3; 4

clamp euglycemic - hyperglycemic PROCEDURE

clamp euglycemic-hyperglycemic

1; 2; 3; 4

diet BEHAVIORAL

diet

1; 2; 3; 4

biopsies for biological and genetic analyses OTHER

biopsies for biological and genetic analyses

1; 2; 3; 4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

CHU de Nantes

Nantes, 44093, France

Location

Related Publications (1)

• 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.

  PMID: 32032671 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Liver Extracts; Diet; Biopsy; Biological Products

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tissue Extracts; Complex Mixtures; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Bertrand Cariou, MD

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

• Michel Krempf, MD

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

• Yassine Zaïr, MD

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

• Eric Letessier, MD

  Nantes University Hospital

  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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2007
• First Posted: January 15, 2007
• Study Start: February 1, 2008
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: April 3, 2014

Record last verified: 2014-04

Locations

FR (1)