Skeletal Muscle Wasting in SARS-CoV-2

Critical Illness Clinical Trial

— SMW  

Official title:

Skeletal Muscle Wasting in SARS-CoV-2 Infected ICU (Intensive Care Unit) Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04698798
• Other study ID #: SMW-CoV-2
• Status: Completed
• Phase: N/A
• Start date: January 2, 2021
• Est. completion date: April 3, 2021

Study information

• Verified date: July 2021
• Source: Hasselt University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: April 3, 2021
• Est. primary completion date: April 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >18 years
• SARS-CoV-2 infection
• Expected stay to ICU of > 7 days

Exclusion Criteria:

• Spinal cord injury
• Chronic use of corticosteroids before hospital admission

Related Conditions & MeSH terms

• Atrophy
• Cachexia
• Critical Illness
• Muscle Atrophy
• Muscle Loss
• Muscle Wasting
• Muscular Atrophy

Intervention

Procedure:
• Muscle Biopsy
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.

Locations

Country	Name	City	State
Belgium	Jessa Ziekenhuis	Hasselt

Sponsors (2)

Lead Sponsor	Collaborator
Hasselt University	Jessa Hospital

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	baseline
Primary	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	Day 7
Primary	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.	Baseline
Primary	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.	Day 7
Secondary	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.	Baseline
Secondary	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.	Day 7
Secondary	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…).	daily between baseline and day 7
Secondary	Mechanical ventilation and oxygen therapy	the modality of oxygen therapy or mechanical ventilation will be monitored each day the patient is in the trial.	daily between baseline and day 7
Secondary	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.	daily between baseline and day 7
Secondary	concommitted medication	All medication that the patients receive will be monitored during the period they participate within the trial.	daily between baseline and day 7
Secondary	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.	Baseline
Secondary	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.	day 7
Secondary	Comorbidities	All comorbidities will be obtained from the patients medical file.	baseline
Secondary	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.	baseline
Secondary	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.	baseline