Genomic and Metabolomic Markers Reflecting the Complications of Hypercortisolism (CUSHINGOMICS)

NCT ID: NCT04840693

Last Updated: 2024-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

540 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-01

Study Completion Date

2026-12-31

Brief Summary

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The excess of glucocorticoid, whether endogenous or exogenous, results in Cushing's syndrome, associating a particular distribution of fats (accumulation in the face and trunk), a decrease in the thickness of the muscles, diabetes, hypertension or osteoporosis.

The level of effects obviously depends on the extent of the excess glucocorticoids, and on the duration of this exposure. However, the manifestations of Cushing's syndrome also depend very much on the sensitivity of each individual to glucocorticoids for each of these conditions. Indeed, for the same duration and level of exposure, some will have diabetes only, others only osteoporosis, others hypertension, while still others will have these three complications. Today the investigators are unable to specify individual risks. For example, will someone develop diabetes when exposed to glucocorticoids? Or on the contrary will blood sugar level remain normal? The same question arises for hypertension and osteoporosis.

The deficiency of glucocorticoid, called adrenal insufficiency, causes fatigue and discomfort. The intensity of the signs depends on the depth of the insufficiency. Here again, there is a large variability in the sensitivity of each individual to glucocorticoids: when one substitutes for adrenal insufficiency at a given dose, some individuals will feel well, while others will still remain tired. The investigators are unable to specify participant's individual requirement.

The aim of this research is to identify factors that determine individual sensitivity to glucocorticoids. For excess glucocorticoids, the investigators are looking for specific molecular markers for each type of glucocorticoid complication: markers for corticosteroid-induced diabetes, corticosteroid-induced hypertension, or corticosteroid-induced osteoporosis.

For adrenal insufficiency, they are also looking for substitute good balance markers for adrenal insufficiency.

To answer the research question, it is planned to include 400 subjects exposed to glucocorticoid excess (by excess of endogenous glucocorticoids or induced by corticosteroid therapy) and 100 subjects with adrenal insufficiency. It is also planned to include 100 subjects without excess glucocorticoids but presenting either diabetes, hypertension or osteoporosis; these subjects will constitute a control group. The investigators will perform a very large number of measurements in small amounts of blood and urine, in order to identify a few marks specifically associated with each of the complications. This research will identify, for every person exposed to glucocorticoids, the probability of developping some complications, and reversely the probability of being exempt from other complications.

Detailed Description

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For each participant, easily accessible biological samples will be taken (blood, urine, saliva). From these samples, a large number of molecular markers will be generated (genomics, metabolomics), in search of signatures specifically associated with each complication.

Three main types of complications will be analyzed: diabetes, hypertension and osteoporosis.

The analysis is planned in 4 stages:

* Identify markers for each type of complication in the context of excess frank glucocorticoids, by comparing affected patients and those not affected for each type of complication.
* Subtraction of non-specific markers of diabetes, hypertension and osteoporosis, identified by the analysis of diabetic, hypertensive and osteoporotic patients who do not have excess glucocorticoids
* Test the performance of these markers in an independent cohort of patients presenting an excess of glucocorticoids at variable levels: frank and at least (endogenous, exogenous)
* Test the performance of these markers in a cohort of patients with substituted adrenal insufficiency

Conditions

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Adult Glucocorticoid Excess Adult Adrenal Insufficiency

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Excess of endogenous glucoglucocorticoids (group 1)

v

Group Type EXPERIMENTAL

Biological samples

Intervention Type BIOLOGICAL

blood, urine, saliva

Complications

Intervention Type OTHER

bone mineral density, diabetes, hypertension, quality of life (quality of life questionnaire SF-36)

Exogenous hypercortisolisms (group 2)

a disease justifying the up-coming start of a glucocorticoid therapy

Group Type EXPERIMENTAL

Biological samples

Intervention Type BIOLOGICAL

blood, urine, saliva

Complications

Intervention Type OTHER

bone mineral density, diabetes, hypertension, quality of life (quality of life questionnaire SF-36)

Adrenal insufficiency (group 3)

chronic adrenal insufficiency

Group Type EXPERIMENTAL

Biological samples

Intervention Type BIOLOGICAL

blood, urine, saliva

Complications

Intervention Type OTHER

bone mineral density, diabetes, hypertension, quality of life (quality of life questionnaire SF-36)

Control (group 4)

without glucocorticoid excess

Group Type OTHER

Biological samples

Intervention Type BIOLOGICAL

blood, urine, saliva

Complications

Intervention Type OTHER

bone mineral density, diabetes, hypertension, quality of life (quality of life questionnaire SF-36)

Interventions

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Biological samples

blood, urine, saliva

Intervention Type BIOLOGICAL

Complications

bone mineral density, diabetes, hypertension, quality of life (quality of life questionnaire SF-36)

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* an endogenous hypercortisolism (group 1)
* a disease justifying the next start of glucocorticoid therapy (group 2)
* chronic adrenal insufficiency (group 3)
* subjects with either diabetes, hypertension or osteoporosis, but without glucocorticoid excess (control group)
* patients will have to be affiliated to a social security scheme
* patients should be able to understand the study and able to express their consent

Exclusion Criteria

* patients with reduced life expectancy, less than 2 years
* pregnant or lactating women
* patients refusing the protocol
* patients under state medical assistance
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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European Union's Horizon 2020 research and innovation programme under grant agreement No 633983

UNKNOWN

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hôpital Cochin

Paris, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Guillaume ASSIE, PhD

Role: CONTACT

+ 33 1 58 41 18 40

Christelle AUGER

Role: CONTACT

+ 33 1 58 41 11 86

Facility Contacts

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Guillaume ASSIE

Role: primary

+ 33 1 58 41 18 40

References

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Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing's syndrome. Lancet. 2006 May 13;367(9522):1605-17. doi: 10.1016/S0140-6736(06)68699-6.

Reference Type BACKGROUND
PMID: 16698415 (View on PubMed)

Charmandari E, Nicolaides NC, Chrousos GP. Adrenal insufficiency. Lancet. 2014 Jun 21;383(9935):2152-67. doi: 10.1016/S0140-6736(13)61684-0. Epub 2014 Feb 4.

Reference Type BACKGROUND
PMID: 24503135 (View on PubMed)

Overman RA, Yeh JY, Deal CL. Prevalence of oral glucocorticoid usage in the United States: a general population perspective. Arthritis Care Res (Hoboken). 2013 Feb;65(2):294-8. doi: 10.1002/acr.21796.

Reference Type BACKGROUND
PMID: 22807233 (View on PubMed)

Fardet L, Petersen I, Nazareth I. Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing's syndrome: cohort study. BMJ. 2012 Jul 30;345:e4928. doi: 10.1136/bmj.e4928.

Reference Type BACKGROUND
PMID: 22846415 (View on PubMed)

Tauchmanova L, Rossi R, Biondi B, Pulcrano M, Nuzzo V, Palmieri EA, Fazio S, Lombardi G. Patients with subclinical Cushing's syndrome due to adrenal adenoma have increased cardiovascular risk. J Clin Endocrinol Metab. 2002 Nov;87(11):4872-8. doi: 10.1210/jc.2001-011766.

Reference Type BACKGROUND
PMID: 12414841 (View on PubMed)

Related Links

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Other Identifiers

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2020-A02714-35

Identifier Type: OTHER

Identifier Source: secondary_id

APHP190799

Identifier Type: -

Identifier Source: org_study_id

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