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

NCT04840693 | Recruiting

• 2 other identifiers: APHP1907992020-A02714-35
• Study Type: interventional
• Target: 540
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Adult Glucocorticoid Excess; Adult Adrenal Insufficiency

Keywords

Hypercortisalism; Glucocorticoids excess; Cushing's syndrome

Outcome Measures

Primary Outcomes (3)

• Identification of molecular markers of glucocorticoid-induced hypertension (diagnosed by oscillometric blood pressure), using genomic and metabolomics measurements

  Genomic measurements will include whole blood methylome, transcriptome and miRNome. Metabolomic measurements will be performed by mass spectrometry in blood plasma and urine, to characterize a large panel of biochemical compounds. Relevant markers identified with these high throughput methods will be combined into a single multidimensional composite predictor.

  3 years

• Identification of markers of glucocorticoid-induced diabetes (diagnosed by HbA1c), using genomic and metabolomics measurements

  Genomic measurements will include whole blood methylome, transcriptome and miRNome. Metabolomic measurements will be performed by mass spectrometry in blood plasma and urine, to characterize a large panel of biochemical compounds. Relevant markers identified with these high throughput methods will be combined into a single multidimensional composite predictor.

  3 years

• Identification of markers of glucocorticoid-induced osteoporosis (diagnosed by bone density test), using genomic and metabolomics measurements

  Genomic measurements will include whole blood methylome, transcriptome and miRNome. Metabolomic measurements will be performed by mass spectrometry in blood plasma and urine, to characterize a large panel of biochemical compounds. Relevant markers identified with these high throughput methods will be combined into a single multidimensional composite predictor.

  3 years

Secondary Outcomes (4)

• Identification of markers of glucocorticoid-induced depression (diagnosed by a psychiatrist evaluation during routine management), using genomic and metabolomics measurements

  3 years

• Identification of markers of glucocorticoid-induced hypercatabolism (diagnosed clinically: bruising, stretch marks and amyotrophy), using genomic and metabolomics measurements

  3 years

• Identification of markers of glucocorticoid-induced abnormal fat distribution (diagnosed clinically), using genomic and metabolomics measurements

  3 years

• Identification of markers of glucocorticoid-induced thromboembolic episode (diagnosed during routine management), using genomic and metabolomics measurements

  3 years

Study Arms (4)

Excess of endogenous glucoglucocorticoids (group 1)

EXPERIMENTAL

v

Biological: Biological samples; Other: Complications

Exogenous hypercortisolisms (group 2)

EXPERIMENTAL

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

Biological: Biological samples; Other: Complications

Adrenal insufficiency (group 3)

EXPERIMENTAL

chronic adrenal insufficiency

Biological: Biological samples; Other: Complications

Control (group 4)

OTHER

without glucocorticoid excess

Biological: Biological samples; Other: Complications

Interventions

Biological samples BIOLOGICAL

blood, urine, saliva

Adrenal insufficiency (group 3); Control (group 4); Excess of endogenous glucoglucocorticoids (group 1); Exogenous hypercortisolisms (group 2)

Complications OTHER

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

Adrenal insufficiency (group 3); Control (group 4); Excess of endogenous glucoglucocorticoids (group 1); Exogenous hypercortisolisms (group 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• European Union's Horizon 2020 research and innovation programme under grant agreement No 633983: collaborator

Study Sites (1)

Hôpital Cochin

Paris, 75014, France

RECRUITING

Related Publications (5)

• 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.

  PMID: 16698415 BACKGROUND

• 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.

  PMID: 24503135 BACKGROUND

• 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.

  PMID: 22807233 BACKGROUND

• 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.

  PMID: 22846415 BACKGROUND

• 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.

  PMID: 12414841 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Adrenal Insufficiency; Cushing Syndrome

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases; Adrenocortical Hyperfunction

Central Study Contacts

Guillaume ASSIE, PhD

CONTACT

+ 33 1 58 41 18 40; guillaume.assie@aphp.fr

Christelle AUGER

CONTACT

+ 33 1 58 41 11 86; christelle.auger@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2021
• First Posted: April 12, 2021
• Study Start: August 1, 2023
• Primary Completion: August 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 9, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)