Physical therapy and NLRP3-related ICU-acquired muscle weakness

Effect of Physical Therapy on NLRP3 Inflammasome Activation and Muscle Atrophy in Critical Illness Myopathy (PT-NLRP3-CIM).

This study will test whether enhanced physical therapy using servo-assisted bed cycling can reduce NLRP3 inflammasome activation and muscle wasting in critically ill patients at risk of critical illness myopathy.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Chile (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 3 sites (Santiago, Metropolitan Region and 2 other locations)
• Trial ID: NCT07017517 on ClinicalTrials.gov

What this trial studies

This randomized interventional study will assign critically ill, septic patients expected to require prolonged mechanical ventilation to either enhanced physical therapy with Motomed Letto® servo-assisted bed cycling plus standard physiotherapy or to standard physiotherapy alone during the early ICU stay. Researchers will measure markers of NLRP3 inflammasome activation and atrogene expression alongside clinical indicators of muscle degradation and function. The trial focuses on patients with high organ failure scores who are at elevated risk for ICU-acquired weakness, and compares molecular and clinical outcomes between the two physical therapy approaches. The aim is to determine whether early, intensified mobilization reduces inflammatory signaling in skeletal muscle and limits atrophy.

Who should consider this trial

Good fit: Adults with sepsis admitted to the ICU who are invasively mechanically ventilated and expected to require ventilation for ≥7 days with sustained high SOFA scores in the early ICU period.

Not a fit: Patients with pre-existing neuromuscular disease, severe coagulopathy or thrombocytopenia, imminent death, expected ICU stay under seven days, or other listed exclusions are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the intervention could lessen muscle atrophy, shorten recovery time, and improve functional outcomes after critical illness.

How similar studies have performed: Preclinical animal studies link NLRP3 inflammasome activation to muscle atrophy and show that exercise or early mobilization can reduce inflammasome markers, but direct clinical evidence for servo-assisted cycling reducing NLRP3 activation in ICU patients is limited and relatively novel.

Eligibility criteria

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.

Where this trial is running

Santiago, Metropolitan Region and 2 other locations

• Clínica INDISA — Santiago, Metropolitan Region, Chile (Recruiting)
• Hospital de Urgencia Asistencia Pública (HUAP) — Santiago, Metropolitan Region, Chile (Recruiting)
• University of Chile — Santiago, Metropolitan Region, Chile (Recruiting)

Study contacts

• Study coordinator: Óscar L Arellano-Pérez, MSc.

Conditions Critical Illness Myopathy; Critical illness myopathy; Physical therapy; NALP3 inflammasome; Muscle atrophy; ICU-acquired weakness