Muscle in Acromegaly and Cushing's Syndrome (MAC)

February 22, 2019 updated by: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Role of Myosteatosis in the Occurrence and Persistence of Residual Muscle Weakness in Patients With Acromegaly and Cushing's Syndrome. Study of the Mechanisms Involved

Cushing's syndrome (CS) and acromegaly determine myopathy and muscle weakness which persist long-term after control of hormone excess. Fatty infiltration in skeletal muscle (myosteatosis) is associated with muscle atrophy, frailty, and increased morbidity and mortality in several human models. The study is aimed at evaluating muscle structure in patients with controlled CS and acromegaly, and correlate it with functional tests of muscle strength. In addition, circulating molecules potentially mediating persistent myopathy in these patients will also be assessed.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Prior chronic exposure to glucocorticoids or growth hormone (GH) determines fat infiltration and persistent impairment of muscle structure in "cured" patients with CS or acromegaly, respectively. All this leads to irreversible changes in muscle strength and performance, markedly affecting morbidity and quality of life of these patients. In particular, muscle weakness would contribute significantly to the development of severe arthropathy associated with excess GH, as well as deterioration of bone status and increased risk of fracture, as described in patients with either CS or acromegaly in remission. Our aim is to evaluate whether muscular MRI is a useful tool for the assessment of myopathy and myosteatosis in these patients. If this is the case, we would have identified a non-invasive test that would allow the follow-up of patients at risk of developing functional motor problems, anticipating the onset of muscle weakness or fatigue and consequent deterioration of their quality of life. On the other hand, we will examine the role of microRNAs, which can suppress the process of myogenic differentiation, as potential modulators of myopathy in these conditions. Indeed, microRNAs could be used in clinical practice as markers to identify patients at risk of myopathy, and develop strategies for their prevention. Clarifying the impact of muscle fat infiltration on muscle strength would allow us to better understand the interaction between muscle and adipose tissue, encouraging research on potential mediators of this relationship, such as myostatin (MSTN) (able to direct the mesenchymal cell muscle towards the formation of adipocytes at the expense of myocytes) and adiponectin (ApN) (which keeps the levels of fat in the muscle low while favoring the formation and regeneration of muscle tissue).

Study Type

Observational

Enrollment (Anticipated)

120

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

  • Spain
    • Please Select
      • Barcelona, Please Select, Spain, 08025
        • Recruiting
        • Hospital de la Santa Creu i Sant Pau
        • Contact:

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

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

  1. Patients with Sd Cushing (CS): 40 women (25-60 years) with CS, with controlled hypercortisolism after treatment and without clinical / biochemical signs of relapse for more than 5 years.
  2. Patients with acromegaly: 40 patients of both sexes (25-60 years) with GH / IGF-I controlled after treatment and without clinical / biochemical signs of relapse for more than 5 years.
  3. Controls: n = 60; normal healthy control paired by age, sex and BMI will be included.

Description

Inclusion Criteria:

  • Patients with Cushing's syndrome or acromegaly who have been in remission for at least 5 years.

Exclusion Criteria:

  • Pregnancy, breastfeeding, chronic liver/kidney disease, chronic treatment with glucocorticoids.

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

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cushing's syndrome

a) Patients with Sd Cushing (SC): 40 women (25-60 years) with SC, with controlled hypercortisolism after treatment and without clinical / biochemical signs of relapse for more than 5 years.

This group will under go the following procedures:

  • muscle MRI
  • dual-energy x-ray absorptiometry
  • muscle ultrasounds
  • blood testing
Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing
3.Dixon, T2 mapping MRI microRNAs
acromegaly

b) Patients with acromegaly: 40 patients of both sexes (25-60 years) with GH / Insulin-like-Growth Factor (IGF-I) controlled after treatment and without clinical / biochemical signs of relapse for more than 5 years.

This group will under go the following procedures:

  • muscle MRI
  • dual-energy x-ray absorptiometry
  • muscle ultrasounds
  • blood testing
Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing
3.Dixon, T2 mapping MRI microRNAs
Healthy controls

Controls: n = 40; normal healthy control paired by age, sex and BMI will be included.

This group will under go the following procedures:

  • muscle MRI
  • dual-energy x-ray absorptiometry
  • muscle ultrasounds
  • blood testing
Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing
3.Dixon, T2 mapping MRI microRNAs

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MRI assessment of fatty infiltration in tigh muscles.
Time Frame: Within one year since recruitment
Quantitative muscle 3Tesla-MRI (mappting T2 and 3.Dixon) will be used. Assessment of fatty infiltration as well as measurement of necrosis and inflammation areas in tigh muscles will be performed.
Within one year since recruitment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
microRNAs
Time Frame: Within one year since recruitment
A bioinformatic study will be carried out to select a set of miRNAs differentially expressed in acromegaly and Cushing's syndrome as compared with controls. The miRNAs will be selected according to the pathophysiological pathways (GO, KEGG) in which they are involved and taking into account the pathophysiology of Cushing's syndrome and acromegaly. Differentially expressed miRNAs will be then related to primary outcome measures.
Within one year since recruitment

Collaborators and Investigators

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

Sponsor

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

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)

February 1, 2018

Primary Completion (Anticipated)

October 31, 2019

Study Completion (Anticipated)

January 31, 2020

Study Registration Dates

First Submitted

August 30, 2018

First Submitted That Met QC Criteria

September 14, 2018

First Posted (Actual)

September 17, 2018

Study Record Updates

Last Update Posted (Actual)

February 25, 2019

Last Update Submitted That Met QC Criteria

February 22, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIBSP-MIO-2017-41

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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