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Alterations of Muscle Secretome Associated With Muscle Atrophy Caused by Glucocorticoids (MYOSECRET)

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ClinicalTrials.gov Identifier: NCT03229395
Recruitment Status : Completed
First Posted : July 25, 2017
Last Update Posted : July 25, 2017
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease
Cushing Syndrome

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Study Type : Observational
Actual Enrollment : 35 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Alterations of Muscle Secretome Associated With Muscle Atrophy Caused by Glucocorticoids
Actual Study Start Date : January 2, 2014
Actual Primary Completion Date : July 13, 2017
Actual Study Completion Date : July 18, 2017


Group/Cohort
patients with Cushing's syndrome
Patients were selected by the PI at the diagnosis.
control patients
Selected patients are matched for age and sex.



Primary Outcome Measures :
  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.


Biospecimen Retention:   Samples With DNA
blood


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03229395


Locations
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Belgium
De Barsy Marie
Brussels, Belgium, 1200
Sponsors and Collaborators
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Investigators
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Study Chair: Marie De Barsy, Nurse Cliniques Universitaires St Luc

Publications of Results:

Other Publications:
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Responsible Party: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier: NCT03229395     History of Changes
Other Study ID Numbers: UCL-MYOSECRET 2014-1
First Posted: July 25, 2017    Key Record Dates
Last Update Posted: July 25, 2017
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:
skeletal muscle
muscle mass
glucocorticoids
biomarkers

Additional relevant MeSH terms:
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Atrophy
Cushing Syndrome
Muscular Atrophy
Pathological Conditions, Anatomical
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs