Skeletal Muscle Regeneration in Survivors of Critical Illness: How to Prevent Satellite Cell Failure?
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorCharles University, Czech Republic
About this trial
Modern intensive care enables patients to survive insults that in the past would have been supralethal. Nonetheless, increased number of survivors suffer from failed functional outcomes associated with prolonged muscle weakness and fatiguability. Whilst alterations of skeletal muscle biology that occur during critical illness slowly disappear over the period of months, muscle weakness remains. Recent pilot studies have shown that muscle weakness is associated with loss and alteration of satellite skeletal muscle cells, which are supposed to proliferate and repair damaged muscle tissue. The pathogenesis of this phenomenon has not been fully understood. In this grant project, we will study function and structure of satellite cells and their organelles (particularly mitochondria) using both classical bioenergetics and advanced microscopic techniques. Satellite cells will be isolated from biopsies taken from critically ill patients with developed muscle weakness in the acute and protracted phase of a disease and after 6 months. In time points, an ultrasound examination of muscle mass will be performed, and metabolism will be assessed using insulin clamps. In an in vitro experiments, we will test also effect of nutritional and anabolic factors and drugs, commonly used in ICU, on satellite cells. In a control branch, cells will be isolated from skeletal muscle of volunteers undergoing elective hip replacement surgery. Results of this study could significantly contribute to understanding of mechanisms leading to ICU acquired muscle weakness and to identify therapeutic strategy in future.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Critically ill patients receiving mechanical ventilation, to be enrolled within 72 hours of admission, who are likely to need 7 days or more of ICU stay
Sudden onset of disease, which can be determined in time (such as trauma, stroke, sudden cardiac arrest etc.)
Informed consent signed by patient or patient's representative
Disqualifiers
Unlikely to survive 6 months
Premorbid downslope functional trajectory or poor performance status (ECOG Gr. 3 or worse) or baseline functional status unknown
Bleeding disorder (INR≥1.5 or PLT< that would preclude muscle biopsies)
Known mitochondrial disease
Trial population
Critically ill patients with sudden onset of disease receiving mechanical ventilation, to be enrolled within 72 hours of admission, who are likely to need 7 days or more of ICU stay. Study population will be compared with control group consisting of patients undergoing hip replacement surgery with a very good to excellent performance status.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
50 Participants
are grouped into 2 trial groupsGroup A: Critically ill patients
Group B: Volunteers with a very good to excellent performance status
Trial outcomes
Primary outcomes
1
Quality of life as per 36-Item Short Form Health Survey (SF-36)
A set of quality-of-life measures. A questionnaire includes questions about: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. The minimum and maximum scores are 0 and 100. A higher score defines a more favorable health state.
Time frame
on day 1802
Changes of muscle mass between baseline, day 7 and day 180
By measurement of musculus rectus femoris cross-sectional area by diagnostic ultrasound.
Time frame
Changes between days 0, 7 and 1803
A measurement of muscle power by Medical Research Council Score
A standardized testing of muscle power \[0-5\] on 12 muscle groups on all 4 limbs using Medical Research Council Score, giving the score from minimum 0 to maximum 60. A higher score defines a more favorable health state, 60 points suggest a normal muscle power.
Time frame
on day 180 (eventually on day 7 if the patient is conscious)4
Changes of mitochondrial function of satellite cells between baseline, day 7 and day 180
Mitochondrial functional parameters will be assessed by Extracellular XF24 Seahorse Analyzer or high-resolution respirometry which enables continous real-time measurement of oxygen consumption in living cells at the baseline and after addition of various substrates, uncouplers and inhibitors of the respiratory chain. This allow to estimate parameters as ATP production, maximal respiratory capacity, respiration in baseline etc. The techniques measure oxygen consumption rate of living cells in pmol/min.
Time frame
Changes between days 0, 7 and 180Secondary outcomes
1
Nitrogen balance measured in g/m2 of body surface area
From collected urine samples, a determination of nitrogen content and 3-methyl histidine levels will be performed (to calculate muscle catabolism rate and nitrogen balance).
Time frame
on first 7 days2
6-minutes walking test to measure aerobic performance
6-minutes of exercise (walking) test used to assess aerobic capacity and endurance.
Time frame
on day 1803
Changes of insulin sensitivity between days 7 and 180
This parameter will be measured after overnight fasting by hyperinsulinaemic euglycemic clamp.
Time frame
Changes between days 7 and 1804
Length of ICU stay in days
A number of days spent on ICU.
Time frame
on day 28Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Charles University, Czech Republic
Lead sponsor
Faculty Hospital Kralovske Vinohrady
Collaborator
Source ClinicalTrials.gov