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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01688349
Recruitment Status : Completed
First Posted : September 19, 2012
Last Update Posted : March 22, 2017
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE August 2, 2012
First Posted Date  ICMJE September 19, 2012
Last Update Posted Date March 22, 2017
Study Start Date  ICMJE October 2012
Actual Primary Completion Date September 16, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2012)
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) ]
Comparison of glucocorticoid pathway genes expression between visceral adipose tissue of Cushing patients and that of normal weight controls matched on sex and age.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2012)
  • 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) ]
    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) ]
    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) ]
    To compare these parameters between SCAT and VAT from Cushing patients
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pattern of Gene Expression in Adipose Tissue From Patients With Cushing Syndrome
Official Title  ICMJE Comparative Study of Subcutaneous and Visceral Adipose Tissue in Patients Affected by Cushing Syndrome Versus 2 Controls Population
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Cushing Syndrome Related to Cortisolic Adenoma
Intervention  ICMJE 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.
Study Arms  ICMJE
  • Experimental: Cushing group
    AT biopsy during partial nephrectomy
    Intervention: Other: analyze the role of glucocorticoid in AT distribution.
  • Controls1
    normal weight metabolic healthy patients having partial nephrectomy with small AT Biopsy.
    Intervention: Other: analyze the role of glucocorticoid in AT distribution.
  • Controls2
    obese individuals already included and having biopsies of VAT and SCAT stocked.
    Intervention: Other: analyze the role of glucocorticoid in AT distribution.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 18, 2012)
90
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 16, 2016
Actual Primary Completion Date September 16, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01688349
Other Study ID Numbers  ICMJE P110906
CRC11001 ( Other Identifier: Assistance Publique )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Bruno Feve, PhD Assistance Publique
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP