Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04698798
Other study ID # SMW-CoV-2
Secondary ID
Status Completed
Phase N/A
First received
Last updated
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
Health authority
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

Study Design


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
See also
  Status Clinical Trial Phase
Completed NCT04551508 - Delirium Screening 3 Methods Study
Recruiting NCT06037928 - Plasma Sodium and Sodium Administration in the ICU
Completed NCT03671447 - Enhanced Recovery After Intensive Care (ERIC) N/A
Recruiting NCT03941002 - Continuous Evaluation of Diaphragm Function N/A
Recruiting NCT04674657 - Does Extra-Corporeal Membrane Oxygenation Alter Antiinfectives Therapy Pharmacokinetics in Critically Ill Patients
Completed NCT04239209 - Effect of Intensivist Communication on Surrogate Prognosis Interpretation N/A
Completed NCT05531305 - Longitudinal Changes in Muscle Mass After Intensive Care N/A
Terminated NCT03335124 - The Effect of Vitamin C, Thiamine and Hydrocortisone on Clinical Course and Outcome in Patients With Severe Sepsis and Septic Shock Phase 4
Completed NCT02916004 - The Use of Nociception Flexion Reflex and Pupillary Dilatation Reflex in ICU Patients. N/A
Recruiting NCT05883137 - High-flow Nasal Oxygenation for Apnoeic Oxygenation During Intubation of the Critically Ill
Completed NCT04479254 - The Impact of IC-Guided Feeding Protocol on Clinical Outcomes in Critically Ill Patients (The IC-Study) N/A
Recruiting NCT04475666 - Replacing Protein Via Enteral Nutrition in Critically Ill Patients N/A
Not yet recruiting NCT04538469 - Absent Visitors: The Wider Implications of COVID-19 on Non-COVID Cardiothoracic ICU Patients, Relatives and Staff
Not yet recruiting NCT04516395 - Optimizing Antibiotic Dosing Regimens for the Treatment of Infection Caused by Carbapenem Resistant Enterobacteriaceae N/A
Withdrawn NCT04043091 - Coronary Angiography in Critically Ill Patients With Type II Myocardial Infarction N/A
Recruiting NCT02922998 - CD64 and Antibiotics in Human Sepsis N/A
Recruiting NCT02989051 - Fluid Restriction Keeps Children Dry Phase 2/Phase 3
Completed NCT03048487 - Protein Consumption in Critically Ill Patients
Completed NCT02899208 - Can an Actigraph be Used to Predict Physical Function in Intensive Care Patients? N/A
Recruiting NCT02163109 - Oxygen Consumption in Critical Illness