Muscle in Acromegaly and Cushing's Syndrome (MAC)

• ClinicalTrials.gov Identifier: NCT03673761
• Recruitment Status: Recruiting
• First Posted: September 17, 2018
• Last Update Posted: February 25, 2019
• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Information provided by (Responsible Party): Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Cushing Syndrome; Acromegaly	Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing

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 Design

• Study Type: Observational
• Estimated Enrollment: 120 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: 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
• Actual Study Start Date: February 1, 2018
• Estimated Primary Completion Date: October 31, 2019
• Estimated Study Completion Date: January 31, 2020

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes
• 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.

Criteria

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.

Contacts and Locations

Contacts

Contact: Elena Valassi, MD, PhD; +34932919000 ext 1942; EValassi@santpau.cat

Locations

Spain

Hospital de la Santa Creu i Sant Pau; Recruiting

Barcelona, Please Select, Spain, 08025

Contact: Elena Valassi, MD, PhD +349329190000 ext 1942 EValassi@santpau.cat

Sponsors and Collaborators

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

More Information

• Responsible Party: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• ClinicalTrials.gov Identifier: NCT03673761
• Other Study ID Numbers: IIBSP-MIO-2017-41
• First Posted: September 17, 2018
• Last Update Posted: February 25, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau:

muscle weakness; myopathy

Additional relevant MeSH terms:

Acromegaly; Muscle Weakness; Cushing Syndrome; Syndrome; Disease; Pathologic Processes; Bone Diseases, Endocrine; Bone Diseases; Musculoskeletal Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Muscular Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Adrenocortical Hyperfunction; Adrenal Gland Diseases