Evolution of Interleukin 7, Fat Mass and Metabolic Profile Before and After Transplantation (IL-7tran)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by University Hospital, Lille.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
University Hospital, Lille
ClinicalTrials.gov Identifier:
NCT01414660
First received: August 10, 2011
Last updated: April 24, 2013
Last verified: June 2012
  Purpose

Three different white adipose tissue-related disorders, whether due to its excess (obesity), absence (lipoatrophies) or aberrant distribution (lipodystrophies), are paradoxically able to induce metabolic insulin resistance syndrome. The respective roles played by 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 yet perfectly understood. In contrast to most organ transplantations that are often complicated by post-transplantation diabetes, diabetes cell therapy is associated with body weight loss, which is possibly related to the antiadipogenic effects of mTOR inhibitors (rapamycin or sirolimus). The aim of this study is thus to determine and monitor blood interleukin-7 and other cytokine levels; metabolic parameters; and fat mass distribution with DEXA and RMN, before and after a immunosuppressive regimen in patients receiving different kinds of transplantation (liver, kidney or islets) with normal weight and no type 2 diabetes before transplantation. In these patients, blood samples will be taken before and after transplantation, as will adipose tissue during the transplantation surgery, in order to constitute a plasma serum, gene and tissue bank for improving our knowledge of disorders linking fat mass, insulin resistance and immunity, especially post-transplantation diabetes.


Condition Intervention
Immunodeficiency Secondary to Organ Transplantation
Procedure: transplantation

Study Type: Observational
Study Design: Observational Model: Case-Only
Official Title: Adipocytes, Insulin Resistance and Immunity: Evolution of Interleukin 7, Fat Mass and Metabolic Profile Before and After Transplantation

Resource links provided by NLM:


Further study details as provided by University Hospital, Lille:

Primary Outcome Measures:
  • interleukin 7 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Interleukin 2 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Interleukin 4 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Interleukin 9 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Interleukin 15 [ Time Frame: 1year ] [ Designated as safety issue: Yes ]
  • Interleukin 21 [ Time Frame: 1year ] [ Designated as safety issue: Yes ]
  • TNFa [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Interleukin 1b [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Interleukin 6 [ Time Frame: 1year ] [ Designated as safety issue: Yes ]
  • Interleukin 8 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Interleukin 10 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Interleukin 18 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • leptin [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • adiponectin [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Blood cells of innate and adaptative immunity analysis [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • fat mass [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • metabolic parameters [ Time Frame: 1 years ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples With DNA

wholeblood and tissue bank


Estimated Enrollment: 30
Study Start Date: June 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
islet
type 1 diabetic patients undergoing islet transplantation
Procedure: transplantation
transplantation of islet, kidney or liver
Other Name: transplantation
liver
non diabetic patients undergoing a liver transplantation
Procedure: transplantation
transplantation of islet, kidney or liver
Other Name: transplantation
kidney
non diabetic patients undergoing a kidney transplantation
Procedure: transplantation
transplantation of islet, kidney or liver
Other Name: transplantation

  Hide Detailed Description

Detailed Description:

Rationale: Due to their ability to store fatty acids and to secrete numerous pro-inflammatory cytokines, adipocytes appear to be key cells 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, whether from its excess (obesity), or its complete (lipoatrophies) or partial absence (lipodystrophies); these 3 different disorders are paradoxically able to induce metabolic insulin resistance syndrome.

Among the involved cytokines, interleukin-7 (IL-7), mostly known for its immune functions, also participates in the quantitative and qualitative balance of fat mass. Thus, IL-7 over-expression in animal models 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 in reactivation of autoimmunity in patients with autoimmune type 1 after islet transplantation.

Otherwise, mammalian target of rapamycin (mTOR) inhibitors have immunosuppressive, metabolic and anti-tumoral properties through different signaling pathways. Rapamycin (or sirolimus) (Rapamune®), an mTOR inhibitor used in islet transplantation, has much greater ability to inhibit adipocyte differentiation and to modulate ß cell function according to the energetic status. In contrast to most organ transplantation, diabetes cell therapy is associated with body weight loss, which is possibly related to the antiadipogenic effects of mTOR inhibitors; the specific role that this plays on the prognostic factors of islet transplantation remains to be determined. Conversely, organ transplantation is usually associated with weight gain, which is involved in the genesis of post-transplantation diabetes, AKA new-onset diabetes after transplantation (NODAT), and long-term vascular complications of transplantation. Adipose tissue redistribution has not yet been studied in patients after transplantation.

The aim of this study is thus to determine blood IL-7 and other cytokine levels; metabolic parameters; and fat mass distribution before and after a immunosuppressive regimen in patients receiving different kinds of transplantation (liver, kidney or islets) with normal weight and no type 2 diabetes before transplantation. In these patients, blood samples will be taken before and after transplantation, as will adipose tissue during the transplantation surgery, in order to constitute a plasma, serum, gene and tissue bank for determining the mechanisms linking fat mass, insulin resistance and immunity, both ex vivo and in vitro.

Patients: The included patients are normal-weight subjects enlisted for liver, kidney or islet transplantation, with no type 2 diabetes (for liver and kidney transplantation).

Methods: Blood IL-7 levels, other immune and/or pro-inflammatory cytokines, lymphocyte immunophenotype, metabolic parameters, and fat mass with non-invasive methods (DEXA and RMN) will be assessed before and one-year after transplantation. Blood, before and after transplantation, as well as adipose tissue during transplantation surgery, will be sampled in order to constitute a blood, gene and tissue bank for defining the inflammatory status of this tissue using histological and molecular analysis.

Primary endpoint: The primary endpoint will be IL-7 blood levels in the different groups according to fat mass, metabolic parameters and immunosuppressive regimen. The hypothesis is that an increase of IL-7 levels, possibly induced by immunosuppressive regimen, is associated with quantitative and/or qualitative disturbances of adipose tissue and the development of insulin resistance.

Expected results and possible implications: This study will enable the consequences of immunosuppression on IL-7 levels, adipose tissue disturbances and glucose metabolism to be determined. Our approach combining clinical investigation and ex vivo and in vitro analysis is original and should result in better understanding of the cellular mechanisms responsible for the inflammatory process initiated in white adipose tissue and accompanying the disorders of this tissue (especially post-transplantation diabetes), thus opening new therapeutic perspectives in a major complication of transplantation.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients undergoing a transplantation in Endocrinology Metabolism department, Nephrology department and Liver Transplantation department in Lille University Hospital, Amiens University Hospital, Caen University Hospital, Rouen University Hospital and Reims University Hospital.

Criteria

Inclusion Criteria:

  • Male and Female
  • More than 18 years old
  • BMI inferior to 30 kg/m2
  • non diabetic patients who need a kidney or a liver transplantation(Glucose blood level <1,26 g/L without any antidiabetic drug)
  • OR included in the islet transplantation protocol because of a C peptide negative brittle or difficult to treat diabetes.
  • cover under the social security

Exclusion Criteria:

  • Unable to receive enlightened information
  • Refusal to sign the consent
  • Auto immune disease (kidney, liver or chronic inflammatory disease)
  • need for a kidney-pancreas transplantation
  • Creatinin > 15 mg / L for patients non concerned by kidney transplantation
  • Sepsis
  • Oestrogens, raloxifene
  • Active alcohol Intoxication
  • Cancers or autoimmune diseases;
  • Psychiatric Pathology
  • Active infection including hepatitis C or HIV;
  • Age under 18 years or above 65 years
  • Participation in another study excluded the possibility of participating in another protocol
  • No cover under the social security
  • Pregnant or lactating women
  • patients under guardianship, persons deprived of liberty
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01414660

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

Locations
France
Amiens University Hospital Recruiting
Amiens, France
Contact: Rachel DESAILLOUD, MD PhD    +33 3 22 45 58 95    r.desailloud@voila.fr   
Caen University Hospital Recruiting
Caen, France
Contact: Yves REZNIK, MD PhD    +33 2 31 06 45 85    reznik-y@chu-caen.fr   
Lille University Hospital Recruiting
Lille, France
Contact: Marie Christin VANTYGHEM, MD PhD    +33 3 20 44 45 35    mc-vantyghem@chru-lille.fr   
Reims University Hospital Recruiting
Reims, France
Contact: Brigitte DELEMER, MD PhD    +33 3 26 78 71 59    bdelemer@chu-reims.fr   
Rouen University Hospital Recruiting
Rouen, France
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, MD, PhD Lille University Hospital
  More Information

No publications provided

Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT01414660     History of Changes
Other Study ID Numbers: 2009_09/0940, 2009_09/0940, B91413-80, PHRC 2009/API
Study First Received: August 10, 2011
Last Updated: April 24, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Lille:
interleukin 7
transplantation
liver
kidney
islet
diabetes

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014