Pattern of Gene Expression in Adipose Tissue From Patients With Cushing Syndrome (LIPOCUSH)
Primary Purpose
Cushing Syndrome Related to Cortisolic Adenoma
Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
analyze the role of glucocorticoid in AT distribution.
Sponsored by
About this trial
This is an interventional basic science trial for Cushing Syndrome Related to Cortisolic Adenoma focused on measuring Glucocorticoids, adipose tissue, Cushing, lipodystrophy, 11 beta-HSD1
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
Sites / Locations
- Hôpital Saint-Antoine, service d'Endocrinologie
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Other
Other
Arm Label
Cushing group
Controls1
Controls2
Arm Description
AT biopsy during partial nephrectomy
normal weight metabolic healthy patients having partial nephrectomy with small AT Biopsy.
obese individuals already included and having biopsies of VAT and SCAT stocked.
Outcomes
Primary Outcome Measures
Comparison between visceral adipose tissue of Cushing patients and that of normal weight controls.
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.
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.
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
To compare these parameters between SCAT and VAT from Cushing patients
Full Information
NCT ID
NCT01688349
First Posted
August 2, 2012
Last Updated
March 21, 2017
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT01688349
Brief Title
Pattern of Gene Expression in Adipose Tissue From Patients With Cushing Syndrome
Acronym
LIPOCUSH
Official Title
Comparative Study of Subcutaneous and Visceral Adipose Tissue in Patients Affected by Cushing Syndrome Versus 2 Controls Population
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
September 16, 2016 (Actual)
Study Completion Date
September 16, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Data Monitoring Committee
No
5. Study Description
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:
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cushing Syndrome Related to Cortisolic Adenoma
Keywords
Glucocorticoids, adipose tissue, Cushing, lipodystrophy, 11 beta-HSD1
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Non-Randomized
Enrollment
90 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cushing group
Arm Type
Experimental
Arm Description
AT biopsy during partial nephrectomy
Arm Title
Controls1
Arm Type
Other
Arm Description
normal weight metabolic healthy patients having partial nephrectomy with small AT Biopsy.
Arm Title
Controls2
Arm Type
Other
Arm Description
obese individuals already included and having biopsies of VAT and SCAT stocked.
Intervention Type
Other
Intervention Name(s)
analyze the role of glucocorticoid in AT distribution.
Intervention Description
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.
Primary Outcome Measure Information:
Title
Comparison between visceral adipose tissue of Cushing patients and that of normal weight controls.
Description
Comparison of glucocorticoid pathway genes expression between visceral adipose tissue of Cushing patients and that of normal weight controls matched on sex and age.
Time Frame
1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
Secondary Outcome Measure Information:
Title
Comparison of the respective SCAT and VAT between Cushing patients and normal weight controls.
Description
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.
Time Frame
1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
Title
Comparison of the respective SCAT and VAT between Cushing patients and obese controls.
Description
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
Time Frame
1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
Title
comparison between SCAT and VAT from Cushing patients
Description
To compare these parameters between SCAT and VAT from Cushing patients
Time Frame
1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruno Feve, PhD
Organizational Affiliation
Assistance Publique
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Saint-Antoine, service d'Endocrinologie
City
Paris
ZIP/Postal Code
75012
Country
France
12. IPD Sharing Statement
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Pattern of Gene Expression in Adipose Tissue From Patients With Cushing Syndrome
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