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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT01688349

Collaborator

(none)

Enrollment

Location

Arms

47.5

Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Cushing Syndrome Related to Cortisolic Adenoma	Other: analyze the role of glucocorticoid in AT distribution.	N/A

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:

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.

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,

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

90 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (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

Study Start Date :

Oct 1, 2012

Actual Primary Completion Date :

Sep 16, 2016

Actual Study Completion Date :

Sep 16, 2016

Arms and Interventions

Arm	Intervention/Treatment
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.
Other: 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.
Other: 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.

Arm

Intervention/Treatment

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.

Other: Controls1

normal weight metabolic healthy patients having partial nephrectomy with small AT Biopsy.

Other: analyze the role of glucocorticoid in AT distribution.

Other: Controls2

obese individuals already included and having biopsies of VAT and SCAT stocked.

Other: analyze the role of glucocorticoid in AT distribution.

Outcome Measures

Primary Outcome Measures

Comparison between visceral adipose tissue of Cushing patients and that of normal weight controls. [1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)]
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. [1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)]
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. [1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)]
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 [1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)]
To compare these parameters between SCAT and VAT from Cushing patients