Cushing SyndromeLYDIANCT05456997
Metabolic Myopathy in Endocrinopathy
An observational study of Cushing Syndrome and Pheochromocytoma, run by Barts & The London NHS Trust at 1 site in United Kingdom.
Trial summary
Endocrine diseases including Cushing's syndrome and phaeochromocytoma/paraganglioma (PPGL) but not Conn's syndrome are associated with muscle wasting and weakness. The study's aim is to identify epigenetic determinants of muscle homeostasis in these conditions following medical treatment and adrenalectomy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cushing Syndrome, Pheochromocytoma, Conns Syndrome
- What is being tested?
- Muscle biopsy
- Type of treatment
- Surgery or procedure
- How many people
- 1 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Mar 2023to 30 Sep 2023
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Inclusion criteria include any consenting adult receiving adrenalectomy surgery for Cushing's or Conn's syndrome or phaeochromocytoma/ paraganglioma (PPGL) at St Bartholomew's Hospital with no evidence of pre-hospital neuromuscular conditions.
Who may be able to join
- Above the age of 18
- Receiving both medical management and adrenalectomy for treatment of Cushing's syndrome or phaeochromocytoma at St Bartholomew's Hospital (SBH)
Who cannot join
- Previous Stroke
- Neuromuscular disease
- Disseminated Malignancy
- Underlying neuromuscular disease
- Paediatrics
- Non-consenting adults
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Barts Heart Centre
London, County (optional), EC1A 7BE
About this study
Official title: Prospective Observational Study of Metabolic Myopathy in Cushing's Syndrome or Pheochromocytoma Patients Undergoing Adrenalectomy
Endocrine diseases including Cushing's syndrome and phaeochromocytoma/paraganglioma (PPGL) but not Conn's syndrome are associated with muscle wasting and weakness. The study's aim is to identify epigenetic determinants of muscle homeostasis in these conditions following medical treatment and adrenalectomy. This is an observational pilot study that will recruit 66 patients from 3 diagnostic groups: Cushing's syndrome (16), PPGL (20) and Conn's syndrome (30). Indices of muscle bulk and strength will be assessed at diagnosis and at outpatient follow-up 6-9 weeks after adrenalectomy. At these times blood and urine will be collected and a muscle biopsy taken from the operation site at the time of surgery. Pathway analysis in these samples will identify potentially novel signalling pathways contributing to muscle wasting via prolonged exposure to high levels of corticosteroid and catecholamines. This will highlight commonalities and differences in pathogenesis of muscle wasting from a variety of different causes. Finally, it will inform identification of novel therapies for muscle atrophy.
Read the detailed description
Muscle wasting and weakness is important because it accounts for a large proportion of the disability associated with disease and normal aging. The annual economic cost in the USA alone has been estimated at $1.8 billion.
The investigators have studied muscle wasting associated with chronic and acute illness, finding a marked dissociation between wasting and disease severity. This indicated that epigenetic and genetic factors may contribute to individual susceptibility to wasting. To analyse factors controlling muscle mass, the investigators have developed a novel clinical model of muscle loss. Hence, in patients undergoing aortic surgery, a large insult is imposed on patients with a background of a disease that leads to muscle wasting (reduced cardiac function). As the timing of the insult is known, the investigators can follow muscle wasting longitudinally. Our recent work using this model has characterised novel muscle signalling pathways that mediate muscle breakdown. Specifically, the investigators found that 50% of patients undergoing cardiac surgery lose significant muscle mass (>10% in the "wasters" group) in the 7 days after uncomplicated surgery, which correlated with loss of strength 7-9 Expression of microRNAs (miRNAs) from imprinted loci (C19MC miRNAs and miR-675) in muscle biopsy samples was strongly associated with subsequent muscle wasting and weakness. Furthermore, expression of these miRNA in myoblasts and animal models confirms their effects on muscle and suggests modes of action through transforming growth factor signalling pathways, ribosome assembly and mitochondrial function. Finally, metabolomic analysis of plasma samples from these patients suggested that exposure to higher levels of active intrinsic corticosteroid, a known cause of sarcopenia, was correlated with muscle loss. Acute muscle wasting (ICU acquired weakness) is associated with high levels of corticosteroids, owing to a defect in deactivation, and shock which is countered with high doses of catecholamines. The investigators will measure miR expression, and longitudinal muscle bulk and strength in patients undergoing adrenalectomy at SBH.
Group 1: Cushing's syndrome caused by very elevated levels of corticosteroids, associated with severe wasting.
Group 2: Phaeochromocytoma and paraganglioma (PPGL) caused by very elevated levels of catecholamines, associated with moderate wasting.
Group 3: Conn's syndrome caused by elevated mineralocorticoid, not associated with muscle wasting (Control group) All patients will be assessed at diagnosis, after medical treatment and after completed reversal of the defect after surgery. Various measures of focal and global strength and function will be recorded alongside measures of muscle bulk. A muscle biopsy from the wound site will be taken at surgery.
One of the key epigenetic determinants of muscle wasting in acute and chronic conditions is micro-RNA (miR-) 424, which targets ribosome synthesis and function as well as insulin sensitivity. The promotor for its' large non-coding RNA precursor contains a steroid responsive region. Therefore overall, the investigators expect miR-424 expression to be correlated with muscle wasting across the 3 patient groups. Mi-RNA profiles will be generated in patient blood and muscle samples: our previous studies have shown that muscle expression of selected mi-RNA is a strong predictor of the response to injury and in patients with chronic respiratory failure (COPD) corresponding circulating levels can be measured in contemporaneous blood samples.
A predictive biomarker (miR expression in blood) would allow a personalised approach to clinical trials for anti-muscle atrophy therapies. The miRNA profiles in blood associated with muscle wasting are likely to be useful predictive biomarkers for several conditions associated with sarcopenia, as evidenced by previous miRNA sets associating with muscle phenotype in COPD and in patients undergoing cardiac surgery.
Pathway analysis will identify potentially novel signalling pathways contributing to muscle wasting via prolonged exposure to high levels of corticosteroid or increased inflammatory sensitivity. This will highlight commonalities and differences in pathogenesis of muscle wasting from a variety of different causes. Finally, it will inform identification of novel therapies for muscle atrophy.
Insensitivity to insulin is a hallmark of many acute and chronic diseases, and a feature of metabolic syndrome. The investigators will be able to determine the potential role of high circulating levels of miR-424, which could constitute a novel therapeutic approach to type 2 diabetes. Similarly, owing to the multi-system insult of cardiac surgery our patient cohorts suffered acute kidney injury and systemic inflammation requiring vasopressors. These data have been collected and could be mined in the future to identify epigenetic determinants and pathways associated with these outcomes.
- Conditions
- Cushing Syndrome, Pheochromocytoma, Conns Syndrome, Metabolic Myopathy
- Being tested
- Muscle biopsy
- Keywords
- Epigenetic control
- Medical subject headings
- Cushing Syndrome, Pheochromocytoma, Hyperaldosteronism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Muscle biopsyProcedure or surgery
Patients will have muscle biopsies taken at time of surgery under general anaesthetic. Open biopsies from the operation field (abdominal wall) will be taken by the surgical team without extending or making new skin incisions. Briefly, muscle samples (approximately 0.5cm3) are excised and haemostasis secured. The muscle biopsies will be snap frozen and stored at -80°C for the analysis of pathways relevant to muscle homeostasis using biochemical and molecular techniques.
| Study group | Role | What they receive |
|---|---|---|
| Cushings syndrome | Patients with Cushing's syndrome treated medically prior to adrenalectomy Receives: Procedure: Muscle biopsy | |
| Phaeochromocytoma and paraganglioma (PPGL) | Patients with PPGL treated medically prior to adrenalectomy Receives: Procedure: Muscle biopsy | |
| Conn's syndrome | Patients with Conn's syndrome treated medically prior to adrenalectomy Receives: Procedure: Muscle biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cross sectional area of the Rectus Femoris (RFcsa)
RFcsa will be calculated using B-mode ultrasound (US) at pre-determined time points
Measured: Day 0/ at presentation to 6-9 week follow up.
Change in Hand Held Dynamometry strength (grip strength)
Hand-held dynamometry will be assessed in both hands (the maximum of 3 attempts)
Measured: Day 0/ at presentation to 6-9 week follow up.
Change in Knee straightening dynamometry
The test will be conducted using a Lafayette Manual Muscle Tester. Joint knee moment (torque) and strength will be measured.
Measured: Day 0/ at presentation to 6-9 week follow up.
Change in Short Physical Performance Battery (SPPB)
SPPB is a measure of patients' functional status: scores range from 0 (worst performance) to 12 (best performance).
Measured: Day 0/ at presentation to 6-9 week follow up.
Change in Lying and Standing Vital Capacity (FVC - forced vital capacity) ratio
Lying and standing vital capacity will be measured using a hand held spirometer
Measured: Day 0/ at presentation to 6-9 week follow up.
Change in bio-impedance indices of body composition
Indices of body composition will be measured by electrical impedance.
Measured: Day 0/ at presentation to 6-9 week follow up.
Change in rectus femoris pixel intensity
Pixel intensity is a measure of muscle quality measured by B mode ultrasound
Measured: Day 0/ at presentation to 6-9 week follow up.
Secondary outcomes (10)
Changes in plasma markers of muscle homeostasis by enzyme-linked immunosorbent assay (ELISA)
Insulin-like growth factor-1
Measured: Day 0/ at presentation & 6-9 week follow up.
Changes in plasma markers of muscle homeostasis by enzyme-linked immunosorbent assay (ELISA)
growth and differentiation factor-15
Measured: Day 0/ at presentation & 6-9 week follow up.
Changes in plasma markers of muscle homeostasis by enzyme-linked immunosorbent assay (ELISA)
resistin
Measured: Day 0/ at presentation & 6-9 week follow up.
Changes in steroid metabolism by mass spectroscopy in blood and urine
cortisol: cortisone ratio
Measured: Day 0/ at presentation to 6-9 week follow up.
Assay in abdominal muscle of markers of muscle atrophy by western blot
Atrogen
Measured: Intra-operatively during adrenalectomy
Assay in abdominal muscle of markers of muscle atrophy by western blot
MURF
Measured: Intra-operatively during adrenalectomy
Unbiased RNA sequencing and targetted qPCR for micro RNAs
Assays undertaken on abdominal muscle
Measured: Intra-operatively during adrenalectomy
Changes in circulating micro-RNAs
Unbiased RNA sequencing of plasma samples and targetted qPCR for micro RNAs
Measured: Day 0/ at presentation to 6-9 week follow up.
Changes in biomarkers of myolysis in urine
Assays for histidine
Measured: Day 0/ at presentation to 6-9 week follow up.
Changes in the metabolome
Mass spectroscopy based unbiased metabolic screen in plasma
Measured: Day 0/ at presentation to 6-9 week follow up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2022
- Study start20 Mar 2023
- Primary completion30 Sep 2023
- Study completion30 Sep 2023
Why it stopped: Loss of research capable staff
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barts & The London NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Imperial College London, Queen Mary University of London
- Responsible party
- Sponsor
- Investigators
- Mark J Griffiths, MB BS, Principal investigator, Bartshealth NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05456997
- Sponsor's protocol ID
- Pending
- Acronym
- LYDIA
- Status last verified
- Apr 2022
- First submitted
- 4 May 2022
- Last updated
- 16 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bloch SA, Donaldson AV, Lewis A, Banya WA, Polkey MI, Griffiths MJ, Kemp PR. MiR-181a: a potential biomarker of acute muscle wasting following elective high-risk cardiothoracic surgery. Crit Care. 2015 Apr 7;19(1):147. doi: 10.1186/s13054-015-0853-5.
PubMed 25888214Kemp PR, Griffiths M, Polkey MI. Muscle wasting in the presence of disease, why is it so variable? Biol Rev Camb Philos Soc. 2019 Jun;94(3):1038-1055. doi: 10.1111/brv.12489. Epub 2018 Dec 26.
PubMed 30588725Donaldson A, Natanek SA, Lewis A, Man WD, Hopkinson NS, Polkey MI, Kemp PR. Increased skeletal muscle-specific microRNA in the blood of patients with COPD. Thorax. 2013 Dec;68(12):1140-9. doi: 10.1136/thoraxjnl-2012-203129. Epub 2013 Jun 28.
PubMed 23814167Connolly M, Paul R, Farre-Garros R, Natanek SA, Bloch S, Lee J, Lorenzo JP, Patel H, Cooper C, Sayer AA, Wort SJ, Griffiths M, Polkey MI, Kemp PR. miR-424-5p reduces ribosomal RNA and protein synthesis in muscle wasting. J Cachexia Sarcopenia Muscle. 2018 Apr;9(2):400-416. doi: 10.1002/jcsm.12266. Epub 2017 Dec 7.
PubMed 29215200Kemp PR, Paul R, Hinken AC, Neil D, Russell A, Griffiths MJ. Metabolic profiling shows pre-existing mitochondrial dysfunction contributes to muscle loss in a model of ICU-acquired weakness. J Cachexia Sarcopenia Muscle. 2020 Oct;11(5):1321-1335. doi: 10.1002/jcsm.12597. Epub 2020 Jul 16.
PubMed 32677363Garros RF, Paul R, Connolly M, Lewis A, Garfield BE, Natanek SA, Bloch S, Mouly V, Griffiths MJ, Polkey MI, Kemp PR. MicroRNA-542 Promotes Mitochondrial Dysfunction and SMAD Activity and Is Elevated in Intensive Care Unit-acquired Weakness. Am J Respir Crit Care Med. 2017 Dec 1;196(11):1422-1433. doi: 10.1164/rccm.201701-0101OC.
PubMed 28809518Ferrau F, Korbonits M. Metabolic comorbidities in Cushing's syndrome. Eur J Endocrinol. 2015 Oct;173(4):M133-57. doi: 10.1530/EJE-15-0354. Epub 2015 Jun 9.
PubMed 26060052
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Observational Study of Metabolic Myopathy in Cushing's Syndrome or Pheochromocytoma Patients Undergoing Adrenalectomy
- ClinicalTrials.gov ID
- NCT05456997
- Acronym / sponsor ID
- LYDIA / Pending
- Conditions
- Cushing Syndrome, Pheochromocytoma, Conns Syndrome, Metabolic Myopathy
- Keywords
- Epigenetic control
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Loss of research capable staff
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Barts & The London NHS TrustUniversity, hospital or other
- Collaborators
- Imperial College London, Queen Mary University of London
- Study start
- 20 Mar 2023 (actual)
- Primary completion
- 30 Sep 2023 (actual)
- Study completion
- 30 Sep 2023 (actual)
- First posted
- 13 Jul 2022 (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.
Endocrine diseases including Cushing's syndrome and phaeochromocytoma/paraganglioma (PPGL) but not Conn's syndrome are associated with muscle wasting and weakness. The study's aim is to identify epigenetic determinants of muscle homeostasis in these conditions following medical treatment and adrenalectomy. This is an observational pilot study that will recruit 66 patients from 3 diagnostic groups: Cushing's syndrome (16), PPGL (20) and Conn's syndrome (30). Indices of muscle bulk and strength will be assessed at diagnosis and at outpatient follow-up 6-9 weeks after adrenalectomy. At these times blood and urine will be collected and a muscle biopsy taken from the operation site at the time of surgery. Pathway analysis in these samples will identify potentially novel signalling pathways contributing to muscle wasting via prolonged exposure to high levels of corticosteroid and catecholamines. This will highlight commonalities and differences in pathogenesis of muscle wasting from a variety of different causes. Finally, it will inform identification of novel therapies for muscle atrophy.
Detailed description
Muscle wasting and weakness is important because it accounts for a large proportion of the disability associated with disease and normal aging. The annual economic cost in the USA alone has been estimated at $1.8 billion.
The investigators have studied muscle wasting associated with chronic and acute illness, finding a marked dissociation between wasting and disease severity. This indicated that epigenetic and genetic factors may contribute to individual susceptibility to wasting. To analyse factors controlling muscle mass, the investigators have developed a novel clinical model of muscle loss. Hence, in patients undergoing aortic surgery, a large insult is imposed on patients with a background of a disease that leads to muscle wasting (reduced cardiac function). As the timing of the insult is known, the investigators can follow muscle wasting longitudinally. Our recent work using this model has characterised novel muscle signalling pathways that mediate muscle breakdown. Specifically, the investigators found that 50% of patients undergoing cardiac surgery lose significant muscle mass (>10% in the "wasters" group) in the 7 days after uncomplicated surgery, which correlated with loss of strength 7-9 Expression of microRNAs (miRNAs) from imprinted loci (C19MC miRNAs and miR-675) in muscle biopsy samples was strongly associated with subsequent muscle wasting and weakness. Furthermore, expression of these miRNA in myoblasts and animal models confirms their effects on muscle and suggests modes of action through transforming growth factor signalling pathways, ribosome assembly and mitochondrial function. Finally, metabolomic analysis of plasma samples from these patients suggested that exposure to higher levels of active intrinsic corticosteroid, a known cause of sarcopenia, was correlated with muscle loss. Acute muscle wasting (ICU acquired weakness) is associated with high levels of corticosteroids, owing to a defect in deactivation, and shock which is countered with high doses of catecholamines. The investigators will measure miR expression, and longitudinal muscle bulk and strength in patients undergoing adrenalectomy at SBH.
Group 1: Cushing's syndrome caused by very elevated levels of corticosteroids, associated with severe wasting.
Group 2: Phaeochromocytoma and paraganglioma (PPGL) caused by very elevated levels of catecholamines, associated with moderate wasting.
Group 3: Conn's syndrome caused by elevated mineralocorticoid, not associated with muscle wasting (Control group) All patients will be assessed at diagnosis, after medical treatment and after completed reversal of the defect after surgery. Various measures of focal and global strength and function will be recorded alongside measures of muscle bulk. A muscle biopsy from the wound site will be taken at surgery.
One of the key epigenetic determinants of muscle wasting in acute and chronic conditions is micro-RNA (miR-) 424, which targets ribosome synthesis and function as well as insulin sensitivity. The promotor for its' large non-coding RNA precursor contains a steroid responsive region. Therefore overall, the investigators expect miR-424 expression to be correlated with muscle wasting across the 3 patient groups. Mi-RNA profiles will be generated in patient blood and muscle samples: our previous studies have shown that muscle expression of selected mi-RNA is a strong predictor of the response to injury and in patients with chronic respiratory failure (COPD) corresponding circulating levels can be measured in contemporaneous blood samples.
A predictive biomarker (miR expression in blood) would allow a personalised approach to clinical trials for anti-muscle atrophy therapies. The miRNA profiles in blood associated with muscle wasting are likely to be useful predictive biomarkers for several conditions associated with sarcopenia, as evidenced by previous miRNA sets associating with muscle phenotype in COPD and in patients undergoing cardiac surgery.
Pathway analysis will identify potentially novel signalling pathways contributing to muscle wasting via prolonged exposure to high levels of corticosteroid or increased inflammatory sensitivity. This will highlight commonalities and differences in pathogenesis of muscle wasting from a variety of different causes. Finally, it will inform identification of novel therapies for muscle atrophy.
Insensitivity to insulin is a hallmark of many acute and chronic diseases, and a feature of metabolic syndrome. The investigators will be able to determine the potential role of high circulating levels of miR-424, which could constitute a novel therapeutic approach to type 2 diabetes. Similarly, owing to the multi-system insult of cardiac surgery our patient cohorts suffered acute kidney injury and systemic inflammation requiring vasopressors. These data have been collected and could be mined in the future to identify epigenetic determinants and pathways associated with these outcomes.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cushings syndrome | – | Procedure: Muscle biopsyPatients with Cushing's syndrome treated medically prior to adrenalectomy |
| Phaeochromocytoma and paraganglioma (PPGL) | – | Procedure: Muscle biopsyPatients with PPGL treated medically prior to adrenalectomy |
| Conn's syndrome | – | Procedure: Muscle biopsyPatients with Conn's syndrome treated medically prior to adrenalectomy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Inclusion criteria include any consenting adult receiving adrenalectomy surgery for Cushing's or Conn's syndrome or phaeochromocytoma/ paraganglioma (PPGL) at St Bartholomew's Hospital with no evidence of pre-hospital neuromuscular conditions.
Key inclusion criteria (2 listed)
- Above the age of 18
- Receiving both medical management and adrenalectomy for treatment of Cushing's syndrome or phaeochromocytoma at St Bartholomew's Hospital (SBH)
Key exclusion criteria (6 listed)
- Previous Stroke
- Neuromuscular disease
- Disseminated Malignancy
- Underlying neuromuscular disease
- Paediatrics
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 |
|---|---|---|
| Muscle biopsyPatients will have muscle biopsies taken at time of surgery under general anaesthetic. Open biopsies from the operation field (abdominal wall) will be taken by the surgical team without extending or making new skin incisions. Briefly, muscle samples (approximately 0.5cm3) are excised and haemostasis secured. The muscle biopsies will be snap frozen and stored at -80°C for the analysis of pathways relevant to muscle homeostasis using biochemical and molecular techniques. | Procedure or surgery | Conn's syndrome, Cushings syndrome, Phaeochromocytoma and paraganglioma (PPGL) |
Primary outcome
Change in cross sectional area of the Rectus Femoris (RFcsa)
Time frame: Day 0/ at presentation to 6-9 week follow up.
RFcsa will be calculated using B-mode ultrasound (US) at pre-determined time points
Change in Hand Held Dynamometry strength (grip strength)
Time frame: Day 0/ at presentation to 6-9 week follow up.
Hand-held dynamometry will be assessed in both hands (the maximum of 3 attempts)
Change in Knee straightening dynamometry
Time frame: Day 0/ at presentation to 6-9 week follow up.
The test will be conducted using a Lafayette Manual Muscle Tester. Joint knee moment (torque) and strength will be measured.
Change in Short Physical Performance Battery (SPPB)
Time frame: Day 0/ at presentation to 6-9 week follow up.
SPPB is a measure of patients' functional status: scores range from 0 (worst performance) to 12 (best performance).
Change in Lying and Standing Vital Capacity (FVC - forced vital capacity) ratio
Time frame: Day 0/ at presentation to 6-9 week follow up.
Lying and standing vital capacity will be measured using a hand held spirometer
Change in bio-impedance indices of body composition
Time frame: Day 0/ at presentation to 6-9 week follow up.
Indices of body composition will be measured by electrical impedance.
Change in rectus femoris pixel intensity
Time frame: Day 0/ at presentation to 6-9 week follow up.
Pixel intensity is a measure of muscle quality measured by B mode ultrasound
10 secondary outcomes
Changes in plasma markers of muscle homeostasis by enzyme-linked immunosorbent assay (ELISA)
Time frame: Day 0/ at presentation & 6-9 week follow up.
Changes in plasma markers of muscle homeostasis by enzyme-linked immunosorbent assay (ELISA)
Time frame: Day 0/ at presentation & 6-9 week follow up.
Changes in plasma markers of muscle homeostasis by enzyme-linked immunosorbent assay (ELISA)
Time frame: Day 0/ at presentation & 6-9 week follow up.
Changes in steroid metabolism by mass spectroscopy in blood and urine
Time frame: Day 0/ at presentation to 6-9 week follow up.
Assay in abdominal muscle of markers of muscle atrophy by western blot
Time frame: Intra-operatively during adrenalectomy
Assay in abdominal muscle of markers of muscle atrophy by western blot
Time frame: Intra-operatively during adrenalectomy
Unbiased RNA sequencing and targetted qPCR for micro RNAs
Time frame: Intra-operatively during adrenalectomy
Changes in circulating micro-RNAs
Time frame: Day 0/ at presentation to 6-9 week follow up.
Changes in biomarkers of myolysis in urine
Time frame: Day 0/ at presentation to 6-9 week follow up.
Changes in the metabolome
Time frame: Day 0/ at presentation to 6-9 week follow up.
Results and safety
The study was stopped early (reason given: Loss of research capable staff). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2023.
- Background: PubMed 25888214Bloch SA, Donaldson AV, Lewis A, Banya WA, Polkey MI, Griffiths MJ, Kemp PR. MiR-181a: a potential biomarker of acute muscle wasting following elective high-risk cardiothoracic surgery. Crit Care. 2015 Apr 7;19(1):147. doi: 10.1186/s13054-015-0853-5.
- Background: PubMed 30588725Kemp PR, Griffiths M, Polkey MI. Muscle wasting in the presence of disease, why is it so variable? Biol Rev Camb Philos Soc. 2019 Jun;94(3):1038-1055. doi: 10.1111/brv.12489. Epub 2018 Dec 26.
- Background: PubMed 23814167Donaldson A, Natanek SA, Lewis A, Man WD, Hopkinson NS, Polkey MI, Kemp PR. Increased skeletal muscle-specific microRNA in the blood of patients with COPD. Thorax. 2013 Dec;68(12):1140-9. doi: 10.1136/thoraxjnl-2012-203129. Epub 2013 Jun 28.
- Background: PubMed 29215200Connolly M, Paul R, Farre-Garros R, Natanek SA, Bloch S, Lee J, Lorenzo JP, Patel H, Cooper C, Sayer AA, Wort SJ, Griffiths M, Polkey MI, Kemp PR. miR-424-5p reduces ribosomal RNA and protein synthesis in muscle wasting. J Cachexia Sarcopenia Muscle. 2018 Apr;9(2):400-416. doi: 10.1002/jcsm.12266. Epub 2017 Dec 7.
- Background: PubMed 32677363Kemp PR, Paul R, Hinken AC, Neil D, Russell A, Griffiths MJ. Metabolic profiling shows pre-existing mitochondrial dysfunction contributes to muscle loss in a model of ICU-acquired weakness. J Cachexia Sarcopenia Muscle. 2020 Oct;11(5):1321-1335. doi: 10.1002/jcsm.12597. Epub 2020 Jul 16.
- Background: PubMed 28809518Garros RF, Paul R, Connolly M, Lewis A, Garfield BE, Natanek SA, Bloch S, Mouly V, Griffiths MJ, Polkey MI, Kemp PR. MicroRNA-542 Promotes Mitochondrial Dysfunction and SMAD Activity and Is Elevated in Intensive Care Unit-acquired Weakness. Am J Respir Crit Care Med. 2017 Dec 1;196(11):1422-1433. doi: 10.1164/rccm.201701-0101OC.
- Background: PubMed 26060052Ferrau F, Korbonits M. Metabolic comorbidities in Cushing's syndrome. Eur J Endocrinol. 2015 Oct;173(4):M133-57. doi: 10.1530/EJE-15-0354. Epub 2015 Jun 9.
- 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.
Mark J Griffiths, MB BS principal investigator
Bartshealth NHS Trust
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 Pheochromocytoma, run by Barts & The London NHS Trust at 1 site in United Kingdom.
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 2 inclusion and 6 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: stopped early, as of the sponsor's last update on 16 Oct 2023. 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 United Kingdom. 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?
The study was stopped early (reason given: Loss of research capable staff). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cross sectional area of the Rectus Femoris (RFcsa) (time frame: Day 0/ at presentation to 6-9 week follow up.). The study lists 7 primary outcomes in all. 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 NCT05456997, which also lists 7 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 16 Oct 2023.