Alterations of Muscle Secretome Associated With Muscle Atrophy Caused by Glucocorticoids

Completed

• Conditions: Cushing Syndrome

• Registration Number: NCT03229395
• Lead Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01-02
• Status Verified: 2016-12
• Study First Submitted: 2016-12-21
• Primary Completion: 2017-07-13
• Study Completion: 2017-07-18
• Study First Submitted QC: 2017-07-24
• Last Update Submitted: 2017-07-24
• Study First Posted: 2017-07-25
• Last Update Posted: 2017-07-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Measurement of BMI in kg/m^2	1 day (one assessment at diagnosis)	Measurement of weight in kilograms and height in meters to determine BMI as BMI=weight/height\^2
Evaluation of daily energy expenditure (DEE) of Cushing's and control patients	1 day (one assessment at diagnosis)	Evaluation of DEE by completing the QAPSE questionnaire.
Measure of body lean mass of Cushing's and control patients	1 day (one assessment at diagnosis)	Bioelectrical Impedance Vector Analysis (BIA) was used for evaluation of lean and fat mass.
Measurement of Mid-arm muscle circumference (MAMC, cm)	1 day (one assessment at diagnosis)	Measurement of triceps skinfold thickness (TSF, in cm), and midarm circumference (MAC, in cm) to determine the MAMC according to the following formula: MAMC= MAC - (Pi x TSF).; MAMC is a bedside anthropometric measurement that estimates somatic protein reserve, an early indicator of nutritional depletion.
Evaluation of quality of life of Cushing's patients	1 day (one assessment at diagnosis)	The CushingQoL questionnaire was used to evaluate quality of life of Cushing's patients
Muscle strenght measurement of Cushing's and control patients	1 day (one assessment at diagnosis)	Evalutation by dynamometer "Jamar type"

Trial Locations

Locations (1)

De Barsy Marie; 🇧🇪 Brussels, Belgium