Muscle in Acromegaly and Cushing's Syndrome

NCT ID: NCT03673761

Last Updated: 2019-02-25

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 120 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-02-01
• Study Completion Date: 2020-01-31

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.

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).

Conditions

Cushing Syndrome; Acromegaly

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

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

MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing

Intervention Type: OTHER

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

MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing

Intervention Type: OTHER

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

MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing

Intervention Type: OTHER

3.Dixon, T2 mapping MRI microRNAs

Interventions

MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing

3.Dixon, T2 mapping MRI microRNAs

Intervention Type: OTHER

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

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

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hospital de la Santa Creu i Sant Pau

Barcelona, Please Select, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Elena Valassi, MD, PhD

Role: CONTACT

EValassi@santpau.cat

+34932919000 ext. 1942

Facility Contacts

Elena Valassi, MD, PhD

Role: primary

EValassi@santpau.cat

+349329190000 ext. 1942

References

Martel-Duguech L, Alonso-Jimenez A, Bascunana H, Diaz-Manera J, Llauger J, Nunez-Peralta C, Montesinos P, Webb SM, Valassi E. Prevalence of sarcopenia after remission of hypercortisolism and its impact on HRQoL. Clin Endocrinol (Oxf). 2021 Nov;95(5):735-743. doi: 10.1111/cen.14568. Epub 2021 Aug 6.

Reference Type: DERIVED

PMID: 34323296 (View on PubMed)

Martel-Duguech L, Alonso-Jimenez A, Bascunana H, Diaz-Manera J, Llauger J, Nunez-Peralta C, Biagetti B, Montesinos P, Webb SM, Valassi E. Thigh Muscle Fat Infiltration Is Associated With Impaired Physical Performance Despite Remission in Cushing's Syndrome. J Clin Endocrinol Metab. 2020 May 1;105(5):dgz329. doi: 10.1210/clinem/dgz329.

Reference Type: DERIVED

PMID: 31912154 (View on PubMed)

Other Identifiers

IIBSP-MIO-2017-41

Identifier Type: -

Identifier Source: org_study_id