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NCT Number: NCT03229395

Alterations of Muscle Secretome Associated With Muscle Atrophy Caused by Glucocorticoids

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.

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Key information

Conditions

Cushing Syndrome Adrenal Gland Diseases Adrenocortical Hyperfunction Endocrine System Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

De Barsy Marie

Brussels, 1200, Belgium

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. Measurement of BMI in kg/m^2

    Time frame: 1 day (one assessment at diagnosis)

    Measurement of weight in kilograms and height in meters to determine BMI as BMI=weight/height^2

  2. Evaluation of quality of life of Cushing's patients

    Time frame: 1 day (one assessment at diagnosis)

    The CushingQoL questionnaire was used to evaluate quality of life of Cushing's patients

  3. Measure of body lean mass of Cushing's and control patients

    Time frame: 1 day (one assessment at diagnosis)

    Bioelectrical Impedance Vector Analysis (BIA) was used for evaluation of lean and fat mass.

  4. Muscle strenght measurement of Cushing's and control patients

    Time frame: 1 day (one assessment at diagnosis)

    Evalutation by dynamometer "Jamar type"

  5. Measurement of Mid-arm muscle circumference (MAMC, cm)

    Time frame: 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.

  6. Evaluation of daily energy expenditure (DEE) of Cushing's and control patients

    Time frame: 1 day (one assessment at diagnosis)

    Evaluation of DEE by completing the QAPSE questionnaire.

Sponsors and collaborators

Lead sponsor

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Other

Registry information

Acronym: MYOSECRET

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Jul 25, 2017
Registry last updated
Jul 25, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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