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Adipocyte, Insulin-resistance and Immunity : Evaluation of Interleukin-7 in Lipodystrophy, Diabetes and Obesity (IL-7norm)

This study is currently recruiting participants.
Verified February 2013 by University Hospital, Lille
Sponsor:
Information provided by (Responsible Party):
Marie-Christine VANTYGHEM, University Hospital, Lille
ClinicalTrials.gov Identifier:
NCT01784289
First received: August 9, 2011
Last updated: February 5, 2013
Last verified: February 2013
History of Changes
  Purpose

White adipose tissue-related diseases spread from excess (obesity) to lack (lipoatrophies) through aberrant distribution (lipodystrophies), these 3 different disorders being paradoxically able to induce a metabolic insulin resistance syndrome. The respective part of quantitative and qualitative anomalies of adipose tissue, gluco- and lipo-toxicity, liver and muscle insulin resistance, low-grade fat inflammation and immune alterations are not perfectly understood in the metabolic syndrome yet. Therefore, the aim of this study is to assess different cytokines, especially interleukin 7, and metabolic parameters as well as fat mass distribution with DEXA and RMN, in different models of fat distribution, including normal-weight, obese and lipodystrophic patients. A plasma serum, gene and adipose tissue bank will be constituted at the same time to improve our knowledge in disorders linking fat mass, insulin resistance and immunity, especially in lipodystrophies, a rare monogenic model of insulin resistance.


Condition
Lipodystrophy
Obesity
Type 2 Diabetes

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Adipocyte, Insulin-resistance and Immunity : Evaluation of Interleukin-7 in Lipodystrophies According to Fat Mass and Glucose Metabolism

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Hospital, Lille:

Primary Outcome Measures:
  • Measure of blood Interleukin 7 [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • measure of blood Interleukins 2 [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • measure of blood interleukin 9 [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • measure of blood Interleukin 15 [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • measure of blood TNF [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • measure of blood IL-1 [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • measure of blood IL-6 [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • measure of blood IL-8 [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • measure of blood IL-10 [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • measure of blood IL-18 [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • measure of blood leptin [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • measure of blood adiponectin [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • Blood count of monocytes/macrophages [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • Blood count of dendritic cells [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
  • Count of blood lymphocytes T [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples With DNA

Wholeblood and tissue bank


Estimated Enrollment: 55
Study Start Date: June 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
normal
Patients with no overweight and no type 2 diabetes
lipodystrophy
patients with a lipodystrophy, most are diabetics
obese non diabetics
Patients with obesity (BMI <30kg/m2), without diabetes
obese diabetics
Patients with obesity (BMI <30 kg/m2), with diabetes

Detailed Description:

Rational: In reason of its ability to store fatty acids and to secrete numerous pro-inflammatory cytokines, the adipocyte appears as a key cell in the regulation of energy metabolism and immune response. Moreover, it has been recently shown that adipocytes play a role in the recruitment of cells involved in innate and adaptive immunity in adipose tissue.

White adipose tissue-related diseases are numerous, spreading from excess (obesity) to a complete (lipoatrophies) or partial lack (lipodystrophies), these 3 different disorders being paradoxically able to induce a metabolic insulin resistance syndrome.

Among the involved cytokines, interleukin-7 (IL-7), mostly known for its immune functions, also participates to the quantitative and qualitative balance of fat mass. Thus, IL-7 over-expression in an animal model induces a lipodystrophic syndrome with insulin resistance whereas in humans, a preliminary study shows that LMNA-linked lipodystrophies are associated with an increase of blood IL-7 levels. IL-7 also participates to reactivation of autoimmunity in patients suffering from auto-immune type 1 after islet transplantation.

Therefore, the aim of this study is to assess different cytokines, especially interleukin 7, and metabolic parameters levels as well as fat mass distribution, in different models of fat distribution, including normal-weighed, obese and lipodystrophic patients. A plasma serum, gene and tissue bank will be constituted in order to improve our knowledge in disorders linking fat mass, insulin resistance and immunity, especially in lipodystrophies, a rare monogenic model of insulin resistance.

Patients: The included patients correspond to subjects of either normal body weight, or obese, or suffering from lipodystrophic syndrome, whatever their type 2 diabetes status.

Methods: Blood IL-7 levels, other immune and/or pro-inflammatory cytokines, lymphocytes immuno-phenotype as well as metabolic parameters will be characterized. Fat mass will be assessed with non-invasive methods (DEXA and RMN). A plasma, serum and gene bank will be constituted. As well as an adipose tissue bank in patients who will have a surgery (especially plastic surgery in lipodystrophic patients), in order to cryo-preserve it and to define the inflammatory status of this tissue thanks to histological and molecular analysis.

Main judgment criteria: The main judgment criteria will be IL-7 blood levels in the different groups according to fat mass and metabolic parameters. The hypothesis is that in humans the quantitative and /or qualitative disturbances of adipose tissue are associated with an increase of IL-7 levels and the development of insulin-resistance.

Awaited results and possible implications: this study will allow to better delineate the immune and inflammatory component associated with alterations of fat mass distribution and glucose metabolism. Our approach combining clinical investigation and ex vivo and laboratory analysis is original and should allow to better understand the cellular mechanisms responsible for the inflammatory process originated in white adipose tissue and accompanying the disorders of this tissue- more especially lipodystrophic syndromes - opening new therapeutic perspectives in common human diseases (obesity, diabetes) on the one hand, and a rare disease (lipodystrophy) on the other hand.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Patients with lipodystrophy : Endocrinology Departments of Lille , Amiens, Caen, Rouen and Reims University hospitals.

Obese (diabetics and non diabetics) and normal weight patients : Endocrinology - Metabolism, Endocrine Surgery and Nutrition Departments, Lille University Hospital

Criteria

Inclusion Criteria:

  • Male and Female
  • More than 18 years old
  • with lipodystrophic syndrome (familial, partial, genetically determined), diabetics or not, obese or not
  • Patients with lipodystrophy non related to a lamine A/C gene mutation, diabetics or not, obese or not
  • Obese without diabetes (BMI> 30)
  • Obese (BMI>30) and diabetes according to ADA criteria
  • Normal weight patients (18< BMI< 25)
  • Agreement for the establishment of a serum bank and a plasma bank

Exclusion Criteria:

  • Unable to receive enlightened information
  • Refusal to sign the consent
  • Corticosteroids (including inhaled), other immunosuppressing treatments (systemic disease for example) or immunomodulators (eg interferon);
  • Creatinin > 15 mg / L
  • Sepsis
  • Progressing cancers or autoimmune diseases;
  • Treatment, disease or other condition that may affect the rate of IL-7 (as some contraceptives with estrogens)
  • Bleeding disorders (due to disease or treatment)
  • Active alcohol Intoxication
  • Psychiatric pathology (after psychiatric consultation)
  • Active infection including hepatitis C or HIV;
  • Age under 18 years
  • Participation in another study excluded the possibility of participating in another protocol
  • BMI > 60
  • Secondary diabetes
  • No social security
  • Pregnant or lactating women, patients under guardianship, persons deprived of liberty
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01784289

Contacts
Contact: Marie Christine VANTYGHEM, PhD +33 3 20 44 45 35 mc-vantyghem@chru-lille.fr
Contact: Marie Christine VANTYGHEM, PhD +33 3 20 44 45 35

Locations
France
Amiens University Hospital Recruiting
Amiens, France, 80054
Contact: Rachel DESAILLOUD, MD PhD     +33 3 22 45 58 95     r.desailloud@voila.fr    
Caen University Hospital Recruiting
Caen, France, 14032
Contact: REZNIK, MD PhD     +33 2 31 06 45 85     reznik-y@chu-caen.fr    
Lille University Hospital Recruiting
Lille, France, 59037
Contact: Marie Christin VANTYGHEM, MD PhD     +33 3 20 44 45 35     mc-vantyghem@chru-lille.fr    
Reims University Hospital Recruiting
Reims, France, 51092
Contact: Brigitte DELEMER, MD PhD     +33 3 26 78 71 59     bdelemer@chu-reims.fr    
Rouen University Hospital Recruiting
Rouen, France, 76031
Contact: Herve LEFEBVRE, MD PhD     +33 2 32 88 90 81     lefebvre@chru-rouen.fr    
Sponsors and Collaborators
University Hospital, Lille
Investigators
Principal Investigator: marie christine VANTYGHEM, pHd Lille University Hospital
  More Information

No publications provided

Responsible Party: Marie-Christine VANTYGHEM, Clinical Professor, University Hospital, Lille
ClinicalTrials.gov Identifier: NCT01784289     History of Changes
Other Study ID Numbers: 2009-A01169-48, 2009_09/0941, B91413-80, PHRC 2009/API
Study First Received: August 9, 2011
Last Updated: February 5, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Lille:
Interleukin 7
adipose tissue

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Insulin Resistance
Lipodystrophy
Obesity
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperinsulinism
 Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on May 21, 2013