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

July 24, 2017 updated by: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
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.

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Actual)

35

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1200
        • De Barsy Marie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

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.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
1 day (one assessment at diagnosis)
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
1 day (one assessment at diagnosis)
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.
1 day (one assessment at diagnosis)
Muscle strenght measurement of Cushing's and control patients
Time Frame: 1 day (one assessment at diagnosis)
Evalutation by dynamometer "Jamar type"
1 day (one assessment at diagnosis)
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.
1 day (one assessment at diagnosis)
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.
1 day (one assessment at diagnosis)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Investigators

  • Study Chair: Marie De Barsy, Nurse, Cliniques Universitaires St Luc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 2, 2014

Primary Completion (Actual)

July 13, 2017

Study Completion (Actual)

July 18, 2017

Study Registration Dates

First Submitted

December 21, 2016

First Submitted That Met QC Criteria

July 24, 2017

First Posted (Actual)

July 25, 2017

Study Record Updates

Last Update Posted (Actual)

July 25, 2017

Last Update Submitted That Met QC Criteria

July 24, 2017

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCL-MYOSECRET 2014-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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