Cushing Syndrome Related to Cortisolic AdenomaLIPOCUSHNCT01688349
Pattern of Gene Expression in Adipose Tissue From Patients With Cushing Syndrome
A study testing analyze the role of glucocorticoid in AT distribution. in people with Cushing Syndrome Related to Cortisolic Adenoma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cushing Syndrome Related to Cortisolic Adenoma
- What is being tested?
- analyze the role of glucocorticoid in AT distribution.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2012to 16 Sep 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Diabetes, renal or hepatic impairment, pregnancy, menopause, HIV or HCV, Cushing's syndrome due to other causes than cortisol adenoma
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparative Study of Subcutaneous and Visceral Adipose Tissue in Patients Affected by Cushing Syndrome Versus 2 Controls Population
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.
Read the 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.
- Being tested
- analyze the role of glucocorticoid in AT distribution.
- Keywords
- Glucocorticoids, adipose tissue, Cushing, lipodystrophy, 11 beta-HSD1
- Medical subject headings
- Lipodystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
analyze the role of glucocorticoid in AT distribution.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.
| Study group | Role | What they receive |
|---|---|---|
| Cushing group | Experimental | AT biopsy during partial nephrectomy Receives: Other: analyze the role of glucocorticoid in AT distribution. |
| Controls1 | Other | normal weight metabolic healthy patients having partial nephrectomy with small AT Biopsy. Receives: Other: analyze the role of glucocorticoid in AT distribution. |
| Controls2 | Other | obese individuals already included and having biopsies of VAT and SCAT stocked. Receives: Other: analyze the role of glucocorticoid in AT distribution. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
Secondary outcomes (3)
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.
Measured: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
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
Measured: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
comparison between SCAT and VAT from Cushing patients
To compare these parameters between SCAT and VAT from Cushing patients
Measured: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2012 (estimated)
- Study startOct 2012
- Primary completion16 Sep 2016
- Study completion16 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cushing Syndrome Related to Cortisolic AdenomaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bruno Feve, PhD, Principal investigator, Assistance Publique
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01688349
- Sponsor's protocol ID
- P110906
- Other IDs
- CRC11001
- Acronym
- LIPOCUSH
- Status last verified
- Mar 2017
- First submitted
- 2 Aug 2012
- Last updated
- 22 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Study of Subcutaneous and Visceral Adipose Tissue in Patients Affected by Cushing Syndrome Versus 2 Controls Population
- ClinicalTrials.gov ID
- NCT01688349
- Acronym / sponsor ID
- LIPOCUSH / P110906
- Keywords
- Glucocorticoids, adipose tissue, Cushing, lipodystrophy, 11 beta-HSD1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- 16 Sep 2016 (actual)
- Study completion
- 16 Sep 2016 (actual)
- First posted
- 19 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cushing group | Experimental | Other: analyze the role of glucocorticoid in AT distribution.AT biopsy during partial nephrectomy |
| Controls1 | Other | Other: analyze the role of glucocorticoid in AT distribution.normal weight metabolic healthy patients having partial nephrectomy with small AT Biopsy. |
| Controls2 | Other | Other: analyze the role of glucocorticoid in AT distribution.obese individuals already included and having biopsies of VAT and SCAT stocked. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (1 listed)
- Diabetes, renal or hepatic impairment, pregnancy, menopause, HIV or HCV, Cushing's syndrome due to other causes than cortisol adenoma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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, Controls2, Cushing group |
Primary outcome
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.
3 secondary outcomes
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)
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 between SCAT and VAT from Cushing patients
Time frame: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2017.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruno Feve, PhD principal investigator
Assistance Publique
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing analyze the role of glucocorticoid in AT distribution. in people with Cushing Syndrome Related to Cortisolic Adenoma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2017.