NLRP3 Inflammasome and Physical Therapy in ICU-Acquired Weakness
ConditionCritical Illness Myopathy
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Chile
About this trial
The goal of this clinical trial is to study whether physical therapy can reduce NLRP3 inflammasome activation and muscle atrophy in patients with critical illness myopathy (CIM). It will also explore the role of NLRP3 inflammasome in the pathophysiology of CIM.
The main questions this study aims to answer are:
Is NLRP3 inflammasome activation associated with muscle atrophy through the upregulation of atrogenes?
Does physical therapy attenuate NLRP3 inflammasome activation in skeletal muscle, thereby contributing to the prevention or reduction of muscle atrophy in CIM?
Researchers will compare enhanced physical therapy using servo-assisted bed cycling (Motomed Letto®) in critically ill patients at risk of developing CIM during the early phase of ICU stay to conventional physical therapy (standard physiotherapy), to assess whether physical therapy reduces NLRP3 inflammasome activation and muscle degradation.
Participants will:
Be randomized to receive either conventional physical therapy or enhanced physical therapy (Motomed Letto®) for 7 consecutive days. A control group of patients without CIM will also be included.
Undergo assessments of NLRP3 activity, muscle atrophy markers, and transcriptomic profiles from serum and vastus lateralis muscle biopsies.
Be clinically evaluated using the SOFA scale and muscle ultrasound for CIM diagnosis.
Be followed up for changes in muscle strength and physical functionality.
Provide sociodemographic and clinical information to be recorded throughout the study.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Medical diagnosis of sepsis upon ICU admission.
Receiving invasive mechanical ventilation with a projected requirement ≥7 days.
SOFA score ≥8 for three consecutive days within the first five days of ICU admission.
Disqualifiers
Neurocritical illness.
Prior malnutrition or cachexia.
Pre-existing neuromuscular disease.
Coagulopathy (severe liver disease or continuous dialysis).
Trial design
Design model
Parallel
Treatments tested in this trial
Motomed Letto® servo-assisted cycling + standard physiotherapy
DeviceServo-assisted cycling using the Motomed Letto® device with a cadence target of 30 revolutions per minute (rpm), performed for 60 minutes twice daily for 7 days. This intervention is administered in addition to standard ICU physiotherapy to critically ill patients at risk of critical illness myopathy (CIM).
Standard physiotherapy
BehavioralStandard physiotherapy including mobilization and passive/active range-of-motion exercises, delivered during routine ICU care for 7 days.
Treatment groups
24 Participants
are divided into 2 treatment groupsGroup A: Enhanced or Additional Physical Therapy GroupExperimental treatment 1 intervention
Group B: Conventional Physical Therapy GroupActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Relative mRNA expression of NLRP3, IL-1β, and IL-18 in muscle tissue (RT-qPCR)
mRNA levels of NLRP3, IL-1β, and IL-18 will be quantified using RT-qPCR from muscle biopsy samples.
Time frame
Baseline and Day 7 (on the final day of intervention)2
Protein expression of phospho-p65S536 and total p65 (Western blot)
Protein levels of phospho-p65 Serine 536 and total p65 will be assessed by Western blot to evaluate NF-κB pathway activation.
Time frame
Baseline and Day 7 (on the final day of intervention)3
Ratio of cleaved/uncleaved caspase-1, IL-1β, and GSDMD-NT (Western blot)
Cleaved forms of IL-1β, caspase-1, and GSDMD-NT will be quantified by Western blot and normalized to precursor forms.
Time frame
Baseline and Day 7 (on the final day of intervention)4
Plasma concentrations of IL-1β and IL-18 (ELISA)
Plasma levels of IL-1β and IL-18 will be measured using ELISA.
Time frame
Baseline and Day 7 (on the final day of intervention)Secondary outcomes
1
Differential expression of genes related to atrophy and inflammasome activation (microarray or nanopore-based RNA sequencing )
Transcriptomic profiling will be performed using microarray or nanopore-based RNA sequencing to identify changes in gene expression related to CIM and NLRP3 activation.
Time frame
Baseline (prior to intervention) and Day 7 of intervention2
Correlation between molecular findings and CIM clinical diagnosis
Correlation analyses will be performed between gene/protein markers and the clinical diagnosis of CIM (based on SOFA score, muscle ultrasound, and clinical assessment with MRC and FSS-ICU scales). Clinical assessments will be conducted once patients regain consciousness, either during ICU stay or follow-up.
Time frame
From recovery of consciousness (in ICU or follow-up) through 90-day follow-upSponsors and contacts
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University of Chile
Lead sponsor
Clinica Indisa
Collaborator
Hospital de Urgencia y Asistencia Pública
Collaborator
Source ClinicalTrials.gov