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

NCT ID: NCT01688349

Last Updated: 2017-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2016-09-16

Brief Summary

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.

Conditions

Cushing Syndrome Related to Cortisolic Adenoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Cushing group

AT biopsy during partial nephrectomy

Group Type: EXPERIMENTAL

analyze the role of glucocorticoid in AT distribution.

Intervention Type: OTHER

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.

Group Type: OTHER

analyze the role of glucocorticoid in AT distribution.

Intervention Type: OTHER

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.

Group Type: OTHER

analyze the role of glucocorticoid in AT distribution.

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruno Feve, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique

Locations

Hôpital Saint-Antoine, service d'Endocrinologie

Paris, , France

Countries

France

Other Identifiers

CRC11001

Identifier Type: OTHER

Identifier Source: secondary_id

P110906

Identifier Type: -

Identifier Source: org_study_id