Clinical trial NCT03229395: Alterations of Muscle Secretome Associated With Muscle Atrophy Caused by Glucocorticoids
Official title: Alterations of Muscle Secretome Associated With Muscle Atrophy Caused by Glucocorticoids
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cushing Syndrome
Keywords: skeletal muscle
muscle mass
glucocorticoids
biomarkers
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
First posted: 2017-07-25
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with Cushing's syndrome are caracterised by elevated circulating glucocorticoid levels generally due to a pitiutary or adrenal adenoma. These patients were compared to heathly control patients who are matched for age and sex.

Brief summary: Several studies have shown that lean mass, in particular muscle mass, is an excellent predictive survival factor in many diseases. A better knowledge of the mechanisms responsible for muscle atrophy and the identification of atrophic process markers are deeply needed for the development of new anti-atrophic therapies. Either as drugs used to treat several medical conditions or as endocrine hormones released in response to many stress situations (e.g., sepsis, cancer, insulinopenia...), glucocorticoids (GC) are recognized to play a major role in skeletal muscle atrophy. Indeed, the inhibition of GC action by a receptor antagonist (RU486) or by muscle-specific invalidation of the GC receptor inhibits the muscle atrophy in these stress situations. Therefore, all these data clearly indicate that GC play a major role in skeletal muscle atrophy observed in several conditions. Emerging evidence has revealed that the skeletal muscle has a secretory function. Human skeletal muscle secretome was first estimated at about 300 proteins by computational analysis and proteomic analysis have recently confirmed these results. Some of these secreted proteins, conceptualized as myokines, can act locally on muscle cells through autocrine/paracrine loops and on surrounding tissues such as muscle blood vessels or can be released into the blood stream to produce systemic effects. One prominent example is interleukin (IL)-6 which is released into circulation by contracting skeletal muscle and can regulate metabolic and inflammatory processes. As IL-6, several other potential myokines have been identified including IL-8, IL-15, insulin-growth factor I (IGF-I), follistatin-like 1 (FSTL1) or fibroblast-growth factor (FGF)-21. Moreover, secreted proteins may also reflected metabolic changes which take place in muscle cells. Indeed, myoblast differentiation is accompanied by dramatic changes in the secreted proteins profile as increased expression of Semaphorins, IGF-I, matrix metalloproteinase (MMP)-2 or Collagens. Thereby, the investigators hypothesized that skeletal muscle atrophy induced by GC is associated with specific alterations of the muscle secretome. The aim of this project is to identify the GC-induced changes in the secretome of human skeletal muscle cells in culture (in vitro approach) and to determine how these changes translate into the circulation of subjects exposed to high concentrations of GC (Cushing's syndrome) (in vivo approach). Characterization of these changes in human subjects should allow to better understand the cellular mechanisms involved in muscle atrophy and might lead to identify circulating biomarkers associated with skeletal muscle atrophy, as telopeptides are for bone tissue.


Eligibility criteria: Inclusion Criteria:

* Pituitary or adrenal endogenous Cushing's syndrome formally demonstrated by the standard endocrinological assessment
* New diagnosis or recurrence or persistent Cushing's syndrome after pituitary surgery

Exclusion Criteria:

* Pseudo Cushing's syndrome
* Paraneoplasic Cushing's syndrome
* Cyclic Cushing's syndrome
* Adrenocortical carcinoma
* Pituitary irradiation during the last six months

Primary outcomes:
measure: Measurement of BMI in kg/m^2
timeFrame: 1 day (one assessment at diagnosis)
measure: Evaluation of quality of life of Cushing's patients
timeFrame: 1 day (one assessment at diagnosis)
measure: Measure of body lean mass of Cushing's and control patients
timeFrame: 1 day (one assessment at diagnosis)
measure: Muscle strenght measurement of Cushing's and control patients
timeFrame: 1 day (one assessment at diagnosis)
measure: Measurement of Mid-arm muscle circumference (MAMC, cm)
timeFrame: 1 day (one assessment at diagnosis)
measure: Evaluation of daily energy expenditure (DEE) of Cushing's and control patients
timeFrame: 1 day (one assessment at diagnosis)
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: De Barsy Marie
Study officials:
affiliation: Cliniques Universitaires St Luc
name: Marie De Barsy, Nurse
role: STUDY_CHAIR
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