NLRP3 Inflammasome and Physical Therapy in ICU-Acquired Weakness (NCT07017517) | Clinical Trial Compass
RecruitingNot Applicable
NLRP3 Inflammasome and Physical Therapy in ICU-Acquired Weakness
Chile24 participantsStarted 2026-04-20
Plain-language summary
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.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* 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.
Exclusion Criteria:
* Neurocritical illness.
* Prior malnutrition or cachexia.
* Pre-existing neuromuscular disease.
* Coagulopathy (severe liver disease or continuous dialysis).
* Thrombocytopenia \<20,000 platelets/μL.
* Prior Clinical Frailty Scale ≥4.
* Lower limb amputation or fractures.
* Ongoing chemotherapy.
* Pregnancy.
* BMI \>35.
* Uncontrolled epilepsy.
* Allergy to ultrasound gel.
* Prior prolonged corticosteroid therapy.
* Expected ICU stay \<7 days.
* Imminent death.
* Legal guardian refusal to provide informed consent.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1This trial is looking at molecular and cellular changes in muscle tissue — including taking muscle biopsies and measuring things like mitochondrial damage and inflammatory markers — so can you walk me through exactly what procedures I or my family member would need to undergo, and how invasive or risky those would be for someone already critically ill in the ICU?
2Since this trial is listed as Phase NA and seems focused on understanding the biological mechanisms behind ICU-acquired weakness rather than testing a new treatment, does that mean there may be no direct therapeutic benefit for the patient enrolled — and if so, how does that weigh against standard physical therapy approaches that are already available?
3The trial is measuring things like muscle fiber diameter, inflammatory proteins, and mitochondrial structure, which sounds like it requires multiple muscle and blood samples over time — given how physically demanding the ICU experience already is, what would the full schedule of procedures look like, and is there a risk that participating could add stress or burden during a critical recovery period?
4Since the study is examining the role of the NLRP3 inflammasome — a pathway linked to inflammation and cell death in muscle — does participating in this trial involve any experimental interventions or changes to physical therapy, or is it purely observational, and how would that affect my loved one's usual care plan?
5Are there patients for whom this kind of research participation would be discouraged — for example, based on the severity of their illness, certain medications they're on, or other conditions — and what questions should we be asking to figure out whether this is even worth considering alongside everything else going on in the ICU?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Relative mRNA expression of NLRP3, IL-1β, and IL-18 in muscle tissue (RT-qPCR)
Timeframe: Baseline and Day 7 (on the final day of intervention)
2
Protein expression of phospho-p65S536 and total p65 (Western blot)
Timeframe: Baseline and Day 7 (on the final day of intervention)
3
Ratio of cleaved/uncleaved caspase-1, IL-1β, and GSDMD-NT (Western blot)
Timeframe: Baseline and Day 7 (on the final day of intervention)
4
Plasma concentrations of IL-1β and IL-18 (ELISA)
Timeframe: Baseline and Day 7 (on the final day of intervention)
5
Expression of oxidative stress markers and cathepsin B (Western blot)
Timeframe: Baseline and Day 7 (on the final day of intervention)
6
Expression of cathepsin B (RT-qPCR)
Timeframe: Baseline and Day 7 (on the final day of intervention)
7
Ultrastructural mitochondrial damage and lysosomal vacuolization (TEM)