Clinical trial NCT04698798: Skeletal Muscle Wasting in SARS-CoV-2
Official title: Skeletal Muscle Wasting in SARS-CoV-2 Infected ICU (Intensive Care Unit) Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cachexia
Muscle Loss
Muscle Wasting
Muscle Atrophy
Critical Illness
Lead sponsor: Hasselt University
Sponsor class: OTHER
Collaborators: name: Jessa Hospital
First posted: 2021-01-07
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Skeletal muscle biopsy
timeFrame: baseline
measure: Skeletal muscle biopsy
timeFrame: Day 7
measure: Electrophysiological test
timeFrame: Baseline
measure: Electrophysiological test
timeFrame: Day 7
Secondary outcomes:
measure: Skeletal muscle biopsy
timeFrame: Baseline
measure: Skeletal muscle biopsy
timeFrame: Day 7
measure: Blood sample analyses
timeFrame: daily between baseline and day 7
measure: Mechanical ventilation and oxygen therapy
timeFrame: daily between baseline and day 7
measure: Dietary intake
timeFrame: daily between baseline and day 7
measure: concommitted medication
timeFrame: daily between baseline and day 7
measure: APACHE II score
timeFrame: Baseline
measure: APACHE II score
timeFrame: day 7
measure: Comorbidities
timeFrame: baseline
measure: Duration from hospital admission to ICU admission
timeFrame: baseline
measure: Symptoms of disease onset and myalgia
timeFrame: baseline
Other outcomes:
Locations:
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
Study officials:
affiliation: Hasselt University
name: Frank Vandenabeele, prof. dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasselt University
name: Sjoerd stevens, drs.
role: STUDY_CHAIR
References: