Pattern of Gene Expression in Adipose Tissue From Patients With Cushing Syndrome (LIPOCUSH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01688349
First received: August 2, 2012
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

The purpose of this trial is to investigate the impact of cortisol on adipose tissue functions, distribution and morphology. Patient with endogenous blood cortisol excess exhibit changes in adipose tissue, with fat gain in the upper trunk, face and neck leading to visceral obesity and features of the metabolic syndrome. The aims of this study will be

  • to compare the pattern of gene expression between visceral and subcutaneous adipose tissue in Cushing patients requiring an adrenalectomy as cortisol adenoma treatment;
  • to compare these patterns of gene expression with those of two control populations:1/ healthy metabolic subjects having a partial nephrectomy, 2/obese patients with similar degree of insulin resistance.

Condition Intervention
Cushing Syndrome Related to Cortisolic Adenoma
Other: analyze the role of glucocorticoid in AT distribution.

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Comparative Study of Subcutaneous and Visceral Adipose Tissue in Patients Affected by Cushing Syndrome Versus 2 Controls Population

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Comparison between visceral adipose tissue of Cushing patients and that of normal weight controls. [ Time Frame: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy) ] [ Designated as safety issue: No ]
    Comparison of glucocorticoid pathway genes expression between visceral adipose tissue of Cushing patients and that of normal weight controls matched on sex and age.


Secondary Outcome Measures:
  • Comparison of the respective SCAT and VAT between Cushing patients and normal weight controls. [ Time Frame: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy) ] [ Designated as safety issue: No ]

    For patients with Cushing and controls1, to compare their respective SCAT and VAT for:

    • The expression of genes involved in differentiation and inflammation of the AT,
    • Morphological aspects: adipocyte size, fibrosis, inflammation, immunohistochemistry.

  • Comparison of the respective SCAT and VAT between Cushing patients and obese controls. [ Time Frame: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy) ] [ Designated as safety issue: No ]
    Comparison of these same parameters(secondary outcome n°1) between Cushing patients and controls2 (matched for sex, age + / -5, HOMA-R + / -1), to differentiate the specific effects of glucocorticoid from the effects of insulin resistance

  • comparison between SCAT and VAT from Cushing patients [ Time Frame: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy) ] [ Designated as safety issue: No ]
    To compare these parameters between SCAT and VAT from Cushing patients


Estimated Enrollment: 90
Study Start Date: October 2012
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cushing group
AT biopsy during partial nephrectomy
Other: analyze the role of glucocorticoid in AT distribution.

The purpose of this trial is to investigate the impact of cortisol on adipose tissue functions, distribution and morphology. Patient with endogenous blood cortisol excess exhibit changes in adipose tissue, with fat gain in the upper trunk, face and neck leading to visceral obesity and features of the metabolic syndrome. The aims of this study will be

  • to compare the pattern of gene expression between visceral and subcutaneous adipose tissue in Cushing patients requiring an adrenalectomy as cortisol adenoma treatment;
  • to compare these patterns of gene expression with those of two control populations:1/ healthy metabolic subjects having a partial nephrectomy, 2/obese patients with similar degree of insulin resistance.
Controls1
normal weight metabolic healthy patients having partial nephrectomy with small AT Biopsy.
Other: analyze the role of glucocorticoid in AT distribution.

The purpose of this trial is to investigate the impact of cortisol on adipose tissue functions, distribution and morphology. Patient with endogenous blood cortisol excess exhibit changes in adipose tissue, with fat gain in the upper trunk, face and neck leading to visceral obesity and features of the metabolic syndrome. The aims of this study will be

  • to compare the pattern of gene expression between visceral and subcutaneous adipose tissue in Cushing patients requiring an adrenalectomy as cortisol adenoma treatment;
  • to compare these patterns of gene expression with those of two control populations:1/ healthy metabolic subjects having a partial nephrectomy, 2/obese patients with similar degree of insulin resistance.
Controls2
obese individuals already included and having biopsies of VAT and SCAT stocked.
Other: analyze the role of glucocorticoid in AT distribution.

The purpose of this trial is to investigate the impact of cortisol on adipose tissue functions, distribution and morphology. Patient with endogenous blood cortisol excess exhibit changes in adipose tissue, with fat gain in the upper trunk, face and neck leading to visceral obesity and features of the metabolic syndrome. The aims of this study will be

  • to compare the pattern of gene expression between visceral and subcutaneous adipose tissue in Cushing patients requiring an adrenalectomy as cortisol adenoma treatment;
  • to compare these patterns of gene expression with those of two control populations:1/ healthy metabolic subjects having a partial nephrectomy, 2/obese patients with similar degree of insulin resistance.

Detailed Description:

Cushing's syndrome is a rare disease resulting from chronic exposure to glucocorticoids (endogenous or iatrogenic) with abnormal fat distribution (lipodystrophy). Glucocorticoids regulate the functions of adipose tissue (AT) targeting adipocyte differentiation as well as anabolic, catabolic and secretory pathways of the adipocyte. However, the mechanisms by which glucocorticoids differentially disrupt the development or metabolism of AT between deep and superficial deposits remain unknown. Among the main effectors of the glucocorticoid signaling pathway, 11 beta-hydroxysteroid deshydrogenase (11beta-HSD1) , that regenerate cortisol from cortisone, is likely a key step in the biological effect of glucocorticoids in AT. Identifying these mechanisms of action of glucocorticoids on different fat depots requires the comparison with fatty deposits derived from two types of control populations: 1/ normal weight individuals without inflammatory or metabolic disorder (controls1); 2/individuals obese matched for the level of insulin resistance (controls2).

Hypothesis: Excess glucocorticoids cause abnormal fat distribution via a direct effect on the various deposits of AT, leading secondarily to insulin resistance.

Primary endpoint: To compare gene expression of glucocorticoid signaling between the visceral AT (VAT) of Cushing patients with that of controls1 (matched for age and sex).

Secondary endpoints:

  1. For patients with Cushing and controls1, to compare their respective subcutaneous AT (SCAT) and VAT for:

    • The expression of genes involved in differentiation and inflammation of the AT,
    • Morphological aspects: adipocyte size, fibrosis, inflammation, immunohistochemistry.
  2. Same parameters for Cushing patients and controls2 (matched for sex, age + / -5, HOMA-R + / -1), to differentiate the specific effects of glucocorticoid from the effects of insulin resistance,
  3. To compare these parameters between SCAT and VAT from Cushing patients. Methodology and experimental design: non-randomized comparative multicenter study with constitution of a biological collection.

Patients will be recruited in endocrinology before adrenalectomy and controls1 in urology. They will have a preoperative assessment and sampling of perirenal AT and SCAT at surgery. Controls2 are already included in the CRC2007-P050318 and will be drawn for matching.

Number of patients needed: We assume the relative gene expression of 11β-HSD1 in the VAT not exposed to glucocorticoids = 0.81 ± 0.121. Our recruitment potential of Cushing patients is 30 patients. With 30 patients per group, we will be able to detect a difference in 11β-HSD1 gene expression in the VAT of Cushing patients at least 15% higher compared to controls1.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cases: Adults with Cushing's syndrome secondary to adrenal adenoma.
  • Controls1: Adults with normal weight: BMI <25, having partial nephrectomy
  • Controls2 adults with common obesity treated by bariatric surgery, BMI> 35kg/m2

Exclusion Criteria:

  • Diabetes, renal or hepatic impairment, pregnancy, menopause, HIV or HCV, Cushing's syndrome due to other causes than cortisol adenoma
  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: NCT01688349

Contacts
Contact: Bruno Feve, PhD 01 49 28 24 06 bruno.feve@sat.aphp.fr
Contact: Camille Vatier, Doctor 01 40 01 13 21 camille.vatier@inserm.fr

Locations
France
Hôpital Saint-Antoine, service d'Endocrinologie Recruiting
Paris, France, 75012
Contact: Bruno Feve, PhD    01 49 28 24 06    bruno.feve@sat.aphp.fr   
Contact: Camille Vatier, Doctor    01 40 01 13 21    camille.vatier@inserm.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Bruno Feve, PhD Assistance Publique
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01688349     History of Changes
Other Study ID Numbers: P110906, CRC11001
Study First Received: August 2, 2012
Last Updated: February 26, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: French Data Protection Authority

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Glucocorticoids
adipose tissue
Cushing
lipodystrophy
11 beta-HSD1

Additional relevant MeSH terms:
Glucocorticoids
Adenoma
Cushing Syndrome
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014