CachexiaSMWNCT04698798
Skeletal Muscle Wasting in SARS-CoV-2
A study testing Muscle Biopsy in people with Cachexia and Muscle Loss, run by Hasselt University at 1 site in Belgium.
Trial summary
The SARS-CoV-2 pandemic causes a major burden on patient and staff admitted/working on the intensive care unit (ICU). Short, and especially long admission on the ICU causes major reductions in skeletal muscle mass (3-4% a day) and strength. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cachexia, Muscle Loss, Muscle Wasting
- What is being tested?
- Muscle Biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteBelgium
- Study dates
- 2 Jan 2021to 3 Apr 2021
- Phase
- Interventional
- 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
Who may be able to join
- Age >18 years
- SARS-CoV-2 infection
- Expected stay to ICU of > 7 days
Who cannot join
- Spinal cord injury
- Chronic use of corticosteroids before hospital admission
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Skeletal Muscle Wasting in SARS-CoV-2 Infected ICU (Intensive Care Unit) Patients
The SARS-CoV-2 pandemic causes a major burden on patient and staff admitted/working on the intensive care unit (ICU). Short, and especially long admission on the ICU causes major reductions in skeletal muscle mass (3-4% a day) and strength. Since it is now possible to reduce mortality on the ICU, short and long-term morbidity should be considered another principal endpoint after SARS-CoV-2 infection. Cachexia is defined as 'a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle mass'. Its clinical features are weight loss, low albumin, anorexia, increased muscle protein breakdown and inflammation. There is strong evidence that cachexia develops rapidly in patients hospitalized for SARS-CoV-2 infection, especially on the ICU. Several mechanisms are believed to induce cachexia in SARS-CoV-2. Firstly, the virus can interact with muscle cells, by binding to the angiotensin converting enzyme 2 (ACE-2). In vitro studies have shown the virus can cause myofibrillar fragmentation into individual sarcomeres, in addition to loss of nuclear DNA in cardiomyocytes. Similar results were found during autopsies. On a cellular level, nothing is known about the effects of SARS-CoV-2 infection on skeletal muscle cells. However, up to 19.4% of patients present with myalgia and elevated levels of creatine kinases (>200U/l), suggesting skeletal muscle injury. Moreover, patients with SARS-CoV-2 infection are shown to have elevated levels of C-reactive protein and other inflammatory cytokines which can all affect skeletal muscles. The above mentioned factors are not the only mediators by which skeletal muscle mass might be affected in SARS-CoV-2. There are other known factors to affect skeletal muscle mass on the ICU, i.e. immobilization and mechanical ventilation, dietary intake (anorexia) and inflammatory cytokines. SARS-CoV-2 infection in combination with bed rest and mechanical ventilation can lead to severe muscle wasting and functional decline resulting in long-term morbidity.
Until know there are no studies investigating acute skeletal muscle wasting in patients infected with SARS-CoV-2 and admitted to the ICU. As a result, there is a need of more in-depth understanding the effects of SARS-CoV-2 infection on muscle wasting. An optimal characterization of these effects may lead to improvement in morbidity and even mortality in the short and long term by the establishment of evidence-based rehabilitation programs for these patients.
- Conditions
- Cachexia, Muscle Loss, Muscle Wasting, Muscle Atrophy, Critical Illness
- Being tested
- Muscle Biopsy
- Medical subject headings
- Cachexia, Muscular Atrophy, Critical Illness
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 be treated for SARS-CoV-2 symptoms on the intensive care unit. During this treatment two muscle biopsies will be obtained with an interval of seven days between them.
| Study group | Role | What they receive |
|---|---|---|
| Skeletal muscle wasting | Experimental | investigating acute skeletal muscle wasting in patients infected with SARS-CoV-2 and admitted to the ICU Receives: Procedure: Muscle Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Skeletal muscle biopsy
A muscle biopsy of the m. vastus lateralis will be obtained at T0, after admission on ICU to evaluate the effects of SARS-CoV-2 infection and ICU admission on skeletal muscle fiber characteristics Muscle biopsy samples will be obtained using a minimally invasive (Bard® Mission® Core Biopsy Instrument (14G 10mm needle)) biopsy technique, under local anaesthesia
Measured: baseline
Skeletal muscle biopsy
A muscle biopsy of the m. vastus lateralis will be obtained at T4, after admission on ICU to evaluate the effects of SARS-CoV-2 infection and ICU admission on skeletal muscle fiber characteristics Muscle biopsy samples will be obtained using a minimally invasive (Bard® Mission® Core Biopsy Instrument (14G 10mm needle)) biopsy technique, under local anaesthesia
Measured: Day 7
Electrophysiological test
Electrophysiological test will be performed at T0 and T1. For nerve conduction studies, one standard motor and one sensory nerve will be evaluated in both upper and lower limbs unilaterally. We define reduced CMAP and SNAP when below the lower limit of normal in both nerves of both limbs. Needle electromyography in rest will be performed unilaterally in one standard proximal and distal muscle in both upper and lower limbs. Abundant SEA was defined as the presence of sustained fibrillation potentials and/or positive sharp waves in at least two muscles of at least two limbs.
Measured: Baseline
Electrophysiological test
Electrophysiological test will be performed at T0 and T1. For nerve conduction studies, one standard motor and one sensory nerve will be evaluated in both upper and lower limbs unilaterally. We define reduced CMAP and SNAP when below the lower limit of normal in both nerves of both limbs. Needle electromyography in rest will be performed unilaterally in one standard proximal and distal muscle in both upper and lower limbs. Abundant SEA was defined as the presence of sustained fibrillation potentials and/or positive sharp waves in at least two muscles of at least two limbs.
Measured: Day 7
Secondary outcomes (11)
Skeletal muscle biopsy
Secondary outcome from the biopsy samples will focus on muscle fiber typing, muscle fiber type-specific CSA, muscle fiber type-specific myonuclear content, muscle fiber type-specific satellite cell content, muscle fiber type-specific capillaries, muscle resident/infiltrating macrophages and others using immunohistochemical stainings. RNA analyses will be done by RT-PCR, and protein analyses by Western Blot for different markers related to oxidative stress, protein synthesis, protein degradation. Myofibrillar damage and viral cell infiltrates and other possible structural changes will be analysed using transmission electron microscopy.
Measured: Baseline
Skeletal muscle biopsy
Secondary outcome from the biopsy samples will focus on muscle fiber typing, muscle fiber type-specific CSA, muscle fiber type-specific myonuclear content, muscle fiber type-specific satellite cell content, muscle fiber type-specific capillaries, muscle resident/infiltrating macrophages and others using immunohistochemical stainings. RNA analyses will be done by RT-PCR, and protein analyses by Western Blot for different markers related to oxidative stress, protein synthesis, protein degradation. Myofibrillar damage and viral cell infiltrates and other possible structural changes will be analysed using transmission electron microscopy.
Measured: Day 7
Blood sample analyses
Standard blood work will be queried during the trial period. We will especially focus on blood marker for muscle damage (such as CK, LDH…) and inflammation (CRP, WBC…).
Measured: daily between baseline and day 7
Mechanical ventilation and oxygen therapy
the modality of oxygen therapy or mechanical ventilation will be monitored each day the patient is in the trial.
Measured: daily between baseline and day 7
Dietary intake
Dietary intake will be monitored every day the patient is within the trial. It will be monitored if the patient receives standard feeding, total parenteral feeding or others. Description: the modality of oxygen therapy or mechanical ventilation will be monitored each day the patient is in the trial.
Measured: daily between baseline and day 7
concommitted medication
All medication that the patients receive will be monitored during the period they participate within the trial.
Measured: daily between baseline and day 7
APACHE II score
Acute Physiology and Chronic Health Evaluation II (APACHE II) is a severity-of-disease classification system. An integer score from 0 to 71 will be computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death.
Measured: Baseline
APACHE II score
Acute Physiology and Chronic Health Evaluation II (APACHE II) is a severity-of-disease classification system. An integer score from 0 to 71 will be computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death.
Measured: day 7
Comorbidities
All comorbidities will be obtained from the patients medical file.
Measured: baseline
Duration from hospital admission to ICU admission
The duration from hospital admission to ICU admission will be noted at T0. This will be done because the amount of days patients are already in the hospital could influence the amount of skeletal muscle atrophy in the ICU.
Measured: baseline
Symptoms of disease onset and myalgia
symptoms of disease onset (fever, cough, anorexia, throat pain, abdominal pain, myalgia, neurological symptoms) will be noted at T0.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2021
- Study start2 Jan 2021
- Primary completion3 Apr 2021
- Study completion3 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CachexiaStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hasselt University
- Sponsor type
- University, hospital or other
- Collaborators
- Jessa Hospital
- Responsible party
- Principal investigator, Frank Vandenabeele, Hasselt University
- Investigators
- Frank Vandenabeele, prof. dr., Principal investigator, Hasselt UniversitySjoerd stevens, drs., Study chair, Hasselt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04698798
- Sponsor's protocol ID
- SMW-CoV-2
- Acronym
- SMW
- Status last verified
- Jul 2021
- First submitted
- 4 Jan 2021
- Last updated
- 8 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Skeletal Muscle Wasting in SARS-CoV-2 Infected ICU (Intensive Care Unit) Patients
- ClinicalTrials.gov ID
- NCT04698798
- Acronym / sponsor ID
- SMW / SMW-CoV-2
- Conditions
- Cachexia, Muscle Loss, Muscle Wasting, Muscle Atrophy, Critical Illness
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Hasselt UniversityUniversity, hospital or other
- Collaborators
- Jessa Hospital
- Study start
- 2 Jan 2021 (actual)
- Primary completion
- 3 Apr 2021 (actual)
- Study completion
- 3 Apr 2021 (actual)
- First posted
- 7 Jan 2021 (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.
The SARS-CoV-2 pandemic causes a major burden on patient and staff admitted/working on the intensive care unit (ICU). Short, and especially long admission on the ICU causes major reductions in skeletal muscle mass (3-4% a day) and strength. Since it is now possible to reduce mortality on the ICU, short and long-term morbidity should be considered another principal endpoint after SARS-CoV-2 infection. Cachexia is defined as 'a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle mass'. Its clinical features are weight loss, low albumin, anorexia, increased muscle protein breakdown and inflammation. There is strong evidence that cachexia develops rapidly in patients hospitalized for SARS-CoV-2 infection, especially on the ICU. Several mechanisms are believed to induce cachexia in SARS-CoV-2. Firstly, the virus can interact with muscle cells, by binding to the angiotensin converting enzyme 2 (ACE-2). In vitro studies have shown the virus can cause myofibrillar fragmentation into individual sarcomeres, in addition to loss of nuclear DNA in cardiomyocytes. Similar results were found during autopsies. On a cellular level, nothing is known about the effects of SARS-CoV-2 infection on skeletal muscle cells. However, up to 19.4% of patients present with myalgia and elevated levels of creatine kinases (>200U/l), suggesting skeletal muscle injury. Moreover, patients with SARS-CoV-2 infection are shown to have elevated levels of C-reactive protein and other inflammatory cytokines which can all affect skeletal muscles. The above mentioned factors are not the only mediators by which skeletal muscle mass might be affected in SARS-CoV-2. There are other known factors to affect skeletal muscle mass on the ICU, i.e. immobilization and mechanical ventilation, dietary intake (anorexia) and inflammatory cytokines. SARS-CoV-2 infection in combination with bed rest and mechanical ventilation can lead to severe muscle wasting and functional decline resulting in long-term morbidity.
Until know there are no studies investigating acute skeletal muscle wasting in patients infected with SARS-CoV-2 and admitted to the ICU. As a result, there is a need of more in-depth understanding the effects of SARS-CoV-2 infection on muscle wasting. An optimal characterization of these effects may lead to improvement in morbidity and even mortality in the short and long term by the establishment of evidence-based rehabilitation programs for these patients.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Skeletal muscle wasting | Experimental | Procedure: Muscle Biopsyinvestigating acute skeletal muscle wasting in patients infected with SARS-CoV-2 and admitted to the ICU |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age >18 years
- SARS-CoV-2 infection
- Expected stay to ICU of > 7 days
Key exclusion criteria (2 listed)
- Spinal cord injury
- Chronic use of corticosteroids before hospital admission
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 be treated for SARS-CoV-2 symptoms on the intensive care unit. During this treatment two muscle biopsies will be obtained with an interval of seven days between them. | Procedure or surgery | Skeletal muscle wasting |
Primary outcome
Skeletal muscle biopsy
Time frame: baseline
A muscle biopsy of the m. vastus lateralis will be obtained at T0, after admission on ICU to evaluate the effects of SARS-CoV-2 infection and ICU admission on skeletal muscle fiber characteristics Muscle biopsy samples will be obtained using a minimally invasive (Bard® Mission® Core Biopsy Instrument (14G 10mm needle)) biopsy technique, under local anaesthesia
Skeletal muscle biopsy
Time frame: Day 7
A muscle biopsy of the m. vastus lateralis will be obtained at T4, after admission on ICU to evaluate the effects of SARS-CoV-2 infection and ICU admission on skeletal muscle fiber characteristics Muscle biopsy samples will be obtained using a minimally invasive (Bard® Mission® Core Biopsy Instrument (14G 10mm needle)) biopsy technique, under local anaesthesia
Electrophysiological test
Time frame: Baseline
Electrophysiological test will be performed at T0 and T1. For nerve conduction studies, one standard motor and one sensory nerve will be evaluated in both upper and lower limbs unilaterally. We define reduced CMAP and SNAP when below the lower limit of normal in both nerves of both limbs. Needle electromyography in rest will be performed unilaterally in one standard proximal and distal muscle in both upper and lower limbs. Abundant SEA was defined as the presence of sustained fibrillation potentials and/or positive sharp waves in at least two muscles of at least two limbs.
Electrophysiological test
Time frame: Day 7
Electrophysiological test will be performed at T0 and T1. For nerve conduction studies, one standard motor and one sensory nerve will be evaluated in both upper and lower limbs unilaterally. We define reduced CMAP and SNAP when below the lower limit of normal in both nerves of both limbs. Needle electromyography in rest will be performed unilaterally in one standard proximal and distal muscle in both upper and lower limbs. Abundant SEA was defined as the presence of sustained fibrillation potentials and/or positive sharp waves in at least two muscles of at least two limbs.
11 secondary outcomes
Skeletal muscle biopsy
Time frame: Baseline
Skeletal muscle biopsy
Time frame: Day 7
Blood sample analyses
Time frame: daily between baseline and day 7
Mechanical ventilation and oxygen therapy
Time frame: daily between baseline and day 7
Dietary intake
Time frame: daily between baseline and day 7
concommitted medication
Time frame: daily between baseline and day 7
APACHE II score
Time frame: Baseline
APACHE II score
Time frame: day 7
Comorbidities
Time frame: baseline
Duration from hospital admission to ICU admission
Time frame: baseline
Symptoms of disease onset and myalgia
Time frame: baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2021.
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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.
Frank Vandenabeele, prof. dr. principal investigator
Hasselt University
Sjoerd stevens, drs. study chair
Hasselt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Muscle Biopsy in people with Cachexia and Muscle Loss, run by Hasselt University at 1 site in Belgium.
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 3 inclusion and 2 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: finished, as of the sponsor's last update on 8 Jul 2021. 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 Belgium. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Skeletal muscle biopsy (time frame: baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Jul 2021; AzTrials last refreshed its copy on 30 Oct 2026.