Cushing SyndromeMACNCT03673761
Muscle in Acromegaly and Cushing's Syndrome
An observational study of Cushing Syndrome and Acromegaly, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Cushing Syndrome, Acromegaly
- What is being tested?
- MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing
- How many people
- 120 participants
- Where
- 1 siteSpain
- Study dates
- 1 Feb 2018to 31 Jan 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- Patients with Cushing's syndrome or acromegaly who have been in remission for at least 5 years.
Who cannot join
- Pregnancy, breastfeeding, chronic liver/kidney disease, chronic treatment with glucocorticoids.
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Hospital de la Santa Creu i Sant Pau
Barcelona, Please Select, 08025
Elena Valassi, MD, PhD, +349329190000 ext. 1942, EValassi@santpau.cat
About this study
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
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.
Read the 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
- Being tested
- MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing
- Keywords
- muscle weakness, myopathy
- Medical subject headings
- Cushing Syndrome, Acromegaly, Muscle Weakness, Muscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testingOther
3.Dixon, T2 mapping MRI microRNAs
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing | |
| 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 Receives: Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing | |
| 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 Receives: Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRI assessment of fatty infiltration in tigh muscles.
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.
Measured: Within one year since recruitment
Secondary outcomes (1)
microRNAs
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.
Measured: Within one year since recruitment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2018
- Study start1 Feb 2018
- Primary completion31 Oct 2019 (estimated)
- Study completion31 Jan 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cushing SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03673761
- Sponsor's protocol ID
- IIBSP-MIO-2017-41
- Acronym
- MAC
- Status last verified
- Feb 2019
- First submitted
- 30 Aug 2018
- Last updated
- 25 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34323296Martel-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.
PubMed 31912154
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03673761
- Acronym / sponsor ID
- MAC / IIBSP-MIO-2017-41
- Conditions
- Cushing Syndrome, Acromegaly
- Keywords
- muscle weakness, myopathy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauUniversity, hospital or other
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 31 Oct 2019 (estimated)
- Study completion
- 31 Jan 2020 (estimated)
- First posted
- 17 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cushing's syndrome | – | Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testinga) 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 |
| acromegaly | – | Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testingb) 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 |
| Healthy controls | – | Other: MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testingControls: 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- Patients with Cushing's syndrome or acromegaly who have been in remission for at least 5 years.
Key exclusion criteria (1 listed)
- Pregnancy, breastfeeding, chronic liver/kidney disease, chronic treatment with glucocorticoids.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRI, dual-energy, x-ray absorptiometry, muscle ultrasounds, blood testing3.Dixon, T2 mapping MRI microRNAs | Other | Cushing's syndrome, Healthy controls, acromegaly |
Primary outcome
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.
1 secondary outcome
microRNAs
Time frame: Within one year since recruitment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2019.
- Derived from this study: PubMed 34323296Martel-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.
- Derived from this study: PubMed 31912154Martel-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cushing Syndrome and Acromegaly, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Elena Valassi, MD, PhD (+34932919000 ext. 1942, EValassi@santpau.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MRI assessment of fatty infiltration in tigh muscles. (time frame: Within one year since recruitment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03673761, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2019.