Critical Illness MyopathyPT-NLRP3-CIMNCT07017517
NLRP3 Inflammasome and Physical Therapy in ICU-Acquired Weakness
A study testing Motomed Letto® servo-assisted cycling + standard physiotherapy and Standard physiotherapy in people with Critical Illness Myopathy, run by University of Chile at 3 sites in Chile.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness Myopathy
- What is being tested?
- Motomed Letto® servo-assisted cycling + standard physiotherapy and Standard physiotherapy
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesChile
- Study dates
- 20 Apr 2026to May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Chile3 sites, 3 recruiting
- Recruiting
Clínica INDISA
Santiago, Metropolitan Region, 7520440
Óscar L Arellano-Pérez, MSc., +56961479414, oscar.arellano@ug.uchile.cl
Felipe A Castillo, MSc., +56992246802, felipe.castillo@indisa.cl
- Recruiting
Hospital de Urgencia Asistencia Pública (HUAP)
Santiago, Metropolitan Region, 8330075
Iván L Hernández Flores, MSc., +56 966768137, ivan.hernandezf@redsalud.gob.cl
Óscar L Arellano-Pérez, MSc., +56961479414, oscar.arellano@ug.uchile.cl
- Recruiting
University of Chile
Santiago, Metropolitan Region, 8380453
About this study
Official title: Effect of Physical Therapy on NLRP3 Inflammasome Activation and Muscle Atrophy in Critical Illness Myopathy (PT-NLRP3-CIM).
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:
Read more
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.
Read the detailed description
Critical illness myopathy (CIM) is a frequent complication in patients admitted to intensive care units (ICUs), characterized by symmetric proximal muscle weakness and respiratory muscle involvement. It has been linked to increased mortality, prolonged hospital stays, and long-term physical disability. CIM may also contribute to post-intensive care syndrome (PICS), which includes persistent cognitive, psychological, and physical impairments. In Chile, approximately 40% of patients with critical illness due to COVID-19 developed this syndrome.
Although several molecular mechanisms have been proposed, the precise etiopathogenesis of CIM remains unclear. Muscle atrophy and contractile dysfunction are hallmark features of CIM. The ubiquitin-proteasome system (UPS) and the upregulation of atrogenes such as MuRF1 and Atrogin-1 have been implicated in its development. In murine models of denervation and sepsis, the NLRP3 inflammasome-a multiprotein complex involved in innate immunity and IL-1β/IL-18 secretion-has been shown to promote muscle atrophy via activation of atrophy-related genes.
Evidence suggests that physical therapy can modulate inflammation at the skeletal muscle level, including downregulation of NLRP3 inflammasome components and IL-1β expression. Mechanical silencing, a major modifiable risk factor in CIM, can be mitigated by early mobilization strategies. However, it remains unknown whether physical therapy directly reduces NLRP3 inflammasome activation and associated muscle atrophy in patients with CIM.
This clinical trial is designed to test the hypothesis that physical therapy decreases NLRP3 inflammasome activity and reduces skeletal muscle atrophy in critically ill patients with CIM. In the early stage of ICU admission, sixteen patients at risk of CIM will be randomized to receive either conventional physical therapy or an enhanced protocol that includes servo-assisted motorized movement therapy (Motomed Letto®), twice daily for 60 minutes. In addition, eight patients without CIM will serve as non-CIM controls.
Muscle biopsy samples from the vastus lateralis will be analyzed to assess histological evidence of muscle atrophy, structural alterations in cellular organelles, and expression of atrophy-related genes. Quantitative real-time PCR (RT-qPCR) will be used to measure mRNA levels of atrogenes, and Western blot will assess protein expression of key mediators of NLRP3 inflammasome signaling. Transcriptomic analysis will be conducted using microarray profiling.
This study will address the following specific aims:
To evaluate the effect of physical therapy on NLRP3 inflammasome activation in skeletal muscle and compare it with non-CIM controls.
To assess the impact of physical therapy on muscle atrophy and explore its relationship with inflammasome activation.
To characterize the gene expression profile of signaling pathways involved in muscle degradation in CIM patients.
To analyze the association between molecular alterations in skeletal muscle and the clinical/ultrasound diagnosis of CIM.
It is expected that enhanced physical therapy will reduce NLRP3 inflammasome activity, attenuate muscle atrophy, and modify gene expression profiles involved in the progression of CIM. These molecular findings are anticipated to correlate with clinical assessments of muscle strength and ultrasound-based diagnosis, supporting the role of early mobilization as a non-pharmacological intervention in the management and prevention of CIM.
- Conditions
- Critical Illness Myopathy
- Being tested
- Motomed Letto® servo-assisted cycling + standard physiotherapy, Standard physiotherapy
- Keywords
- Critical illness myopathy, Physical therapy, NALP3 inflammasome, Muscle atrophy, ICU-acquired weakness
- Medical subject headings
- Muscular Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Motomed Letto® servo-assisted cycling + standard physiotherapyDevice
Also called Motomed Letto®, Additional Physical Therapy, Enhanced Physical Therapy
Servo-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 physiotherapyBehavioural
Also called Conventional physical therapy, routine ICU physiotherapy
Standard physiotherapy including mobilization and passive/active range-of-motion exercises, delivered during routine ICU care for 7 days.
| Study group | Role | What they receive |
|---|---|---|
| Enhanced or Additional Physical Therapy Group | Experimental | Critically ill patients at risk of developing CIM will receive enhanced (additional) physical therapy consisting of standard physiotherapy plus servo-assisted lower-limb cycling using the Motomed Letto® device. Therapy will be delivered twice daily, 60 minutes per session, for 7 consecutive days during the early ICU stay. Muscle biopsies from the vastus lateralis will be collected for histological and molecular analyses. Receives: Device: Motomed Letto® servo-assisted cycling + standard physiotherapy |
| Conventional Physical Therapy Group | Active comparator | Critically ill patients at risk of CIM will receive standard physiotherapy delivered according to institutional ICU rehabilitation protocols. The intervention is delivered at the same frequency and clinical stage as the enhanced therapy group. Receives: Behavioral: Standard physiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Day 7 (on the final day of intervention)
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.
Measured: Baseline and Day 7 (on the final day of intervention)
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.
Measured: Baseline and Day 7 (on the final day of intervention)
Plasma concentrations of IL-1β and IL-18 (ELISA)
Plasma levels of IL-1β and IL-18 will be measured using ELISA.
Measured: Baseline and Day 7 (on the final day of intervention)
Expression of oxidative stress markers and cathepsin B (Western blot)
Protein carbonylation, nitration, and cathepsin B expression will be analyzed by Western blot.
Measured: Baseline and Day 7 (on the final day of intervention)
Expression of cathepsin B (RT-qPCR)
Cathepsin B expression will be analyzed by RT-qPCR.
Measured: Baseline and Day 7 (on the final day of intervention)
Ultrastructural mitochondrial damage and lysosomal vacuolization (TEM)
Mitochondrial damage and lysosomal vacuole volume will be assessed by transmission electron microscopy.
Measured: Baseline and Day 7 (on the final day of intervention)
Muscle fiber diameter (immunofluorescence)
Fiber diameter in 10 µm cryosections will be measured using anti-laminin immunofluorescence.
Measured: Baseline and Day 7 (on the final day of intervention)
mRNA expression of atrogenes: MuRF1, Atrogin-1, MUSA1, TRIM62, TRIM32
Atrogene mRNA levels will be quantified using RT-qPCR from muscle biopsies.
Measured: Baseline and Day 7 (on the final day of intervention)
Myosin/actin ratio (Western blot)
Myosin and actin protein levels will be analyzed by Western blot to assess the molecular diagnosis of CIM.
Measured: Baseline and Day 7 (on the final day of intervention)
Sarcomeric organization (TEM)
Evaluation of sarcomeric structure in cryosections using transmission electron microscopy.
Measured: Baseline and Day 7 (on the final day of intervention)
Secondary outcomes (2)
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.
Measured: Baseline (prior to intervention) and Day 7 of intervention
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.
Measured: From recovery of consciousness (in ICU or follow-up) through 90-day follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2025
- Study start20 Apr 2026
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (104)Papers the sponsor has linked to this study.
- Other trials for Critical Illness MyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Chile
- Sponsor type
- University, hospital or other
- Collaborators
- Clinica Indisa, Hospital de Urgencia y Asistencia Pública
- Responsible party
- Principal investigator, Oscar Arellano, University of Chile
- Investigators
- Paola A Llanos, PhD, Study director, University of Chile
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07017517
- Sponsor's protocol ID
- 001-2025
- Acronym
- PT-NLRP3-CIM
- Status last verified
- Sep 2025
- First submitted
- 26 May 2025
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) will not be shared in order to uphold ethical standards of patient confidentiality. All data collected will be treated in strict compliance with ethical and regulatory guidelines to protect participant identity. The dissemination of results will occur exclusively in aggregate form, fully anonymized, and only in scientific or academic settings, such as peer-reviewed publications or presentations at conferences.
Publications
Americo-Da-Silva L, Aguilera J, Quinteros-Waltemath O, Sanchez-Aguilera P, Russell J, Cadagan C, Meneses-Valdes R, Sanchez G, Estrada M, Jorquera G, Barrientos G, Llanos P. Activation of the NLRP3 Inflammasome Increases the IL-1beta Level and Decreases GLUT4 Translocation in Skeletal Muscle during Insulin Resistance. Int J Mol Sci. 2021 Sep 23;22(19):10212. doi: 10.3390/ijms221910212.
PubMed 34638553Neves M Jr, Barreto G, Boobis L, Harris R, Roschel H, Tricoli V, Ugrinowitsch C, Negrao C, Gualano B. Incidence of adverse events associated with percutaneous muscular biopsy among healthy and diseased subjects. Scand J Med Sci Sports. 2012 Apr;22(2):175-8. doi: 10.1111/j.1600-0838.2010.01264.x. Epub 2011 Mar 10.
PubMed 21392121Raithatha A, Ashraghi MR, Lord C, Limback-Stanic C, Viegas S, Amiras D. Ultrasound-guided muscle biopsy: a practical alternative for investigation of myopathy. Skeletal Radiol. 2020 Nov;49(11):1855-1859. doi: 10.1007/s00256-020-03484-y. Epub 2020 Jun 9.
PubMed 32519182Kho ME, Molloy AJ, Clarke F, Herridge MS, Koo KK, Rudkowski J, Seely AJ, Pellizzari JR, Tarride JE, Mourtzakis M, Karachi T, Cook DJ; Canadian Critical Care Trials Group. CYCLE pilot: a protocol for a pilot randomised study of early cycle ergometry versus routine physiotherapy in mechanically ventilated patients. BMJ Open. 2016 Apr 8;6(4):e011659. doi: 10.1136/bmjopen-2016-011659.
PubMed 27059469Moisi L, Mino JC, Guidet B, Vallet H. Frailty assessment in critically ill older adults: a narrative review. Ann Intensive Care. 2024 Jun 18;14(1):93. doi: 10.1186/s13613-024-01315-0.
PubMed 38888743Mahoney DJ, Carey K, Fu MH, Snow R, Cameron-Smith D, Parise G, Tarnopolsky MA. Real-time RT-PCR analysis of housekeeping genes in human skeletal muscle following acute exercise. Physiol Genomics. 2004 Jul 8;18(2):226-31. doi: 10.1152/physiolgenomics.00067.2004.
PubMed 15161965Gonzalez-Seguel F, Camus-Molina A, Carcamo M, Hiser S, Needham DM, Leppe J. Inter-observer reliability of trained physiotherapists on the Functional Status Score for the Intensive Care Unit Chilean-Spanish version. Physiother Theory Pract. 2022 Feb;38(2):365-371. doi: 10.1080/09593985.2020.1753272. Epub 2020 Apr 22.
PubMed 32316800Pardo E, El Behi H, Boizeau P, Verdonk F, Alberti C, Lescot T. Reliability of ultrasound measurements of quadriceps muscle thickness in critically ill patients. BMC Anesthesiol. 2018 Dec 27;18(1):205. doi: 10.1186/s12871-018-0647-9.
PubMed 30591032Hadda V, Khilnani GC, Kumar R, Dhunguna A, Mittal S, Khan MA, Madan K, Mohan A, Guleria R. Intra- and Inter-observer Reliability of Quadriceps Muscle Thickness Measured with Bedside Ultrasonography by Critical Care Physicians. Indian J Crit Care Med. 2017 Jul;21(7):448-452. doi: 10.4103/ijccm.IJCCM_426_16.
PubMed 28808365Turan Z, Topaloglu M, Ozyemisci Taskiran O. Medical Research Council-sumscore: a tool for evaluating muscle weakness in patients with post-intensive care syndrome. Crit Care. 2020 Sep 18;24(1):562. doi: 10.1186/s13054-020-03282-x. No abstract available.
PubMed 32948221Pietrangelo T, Perni S, Di Tano G, Fano-Illic G, Franzini-Armstrong C. A method for the ultrastructural preservation of tiny percutaneous needle biopsy material from skeletal muscle. Int J Mol Med. 2013 Oct;32(4):965-70. doi: 10.3892/ijmm.2013.1454. Epub 2013 Jul 23.
PubMed 23900509Hodgson CL, Stiller K, Needham DM, Tipping CJ, Harrold M, Baldwin CE, Bradley S, Berney S, Caruana LR, Elliott D, Green M, Haines K, Higgins AM, Kaukonen KM, Leditschke IA, Nickels MR, Paratz J, Patman S, Skinner EH, Young PJ, Zanni JM, Denehy L, Webb SA. Expert consensus and recommendations on safety criteria for active mobilization of mechanically ventilated critically ill adults. Crit Care. 2014 Dec 4;18(6):658. doi: 10.1186/s13054-014-0658-y.
PubMed 25475522Nickels MR, Aitken LM, Walsham J, Barnett AG, McPhail SM. Critical Care Cycling Study (CYCLIST) trial protocol: a randomised controlled trial of usual care plus additional in-bed cycling sessions versus usual care in the critically ill. BMJ Open. 2017 Oct 22;7(10):e017393. doi: 10.1136/bmjopen-2017-017393.
PubMed 29061618Kho ME, Berney S, Pastva AM, Kelly L, Reid JC, Burns KEA, Seely AJ, D'Aragon F, Rochwerg B, Ball I, Fox-Robichaud AE, Karachi T, Lamontagne F, Archambault PM, Tsang JL, Duan EH, Muscedere J, Verceles AC, Serri K, English SW, Reeve BK, Mehta S, Rudkowski JC, Heels-Ansdell D, O'Grady HK, Strong G, Obrovac K, Ajami D, Camposilvan L, Tarride JE, Thabane L, Herridge MS, Cook DJ. Early In-Bed Cycle Ergometry in Mechanically Ventilated Patients. NEJM Evid. 2024 Jul;3(7):EVIDoa2400137. doi: 10.1056/EVIDoa2400137. Epub 2024 Jun 12.
PubMed 38865147Nickels MR, Aitken LM, Barnett AG, Walsham J, King S, Gale NE, Bowen AC, Peel BM, Donaldson SL, Mealing STJ, McPhail SM. Effect of in-bed cycling on acute muscle wasting in critically ill adults: A randomised clinical trial. J Crit Care. 2020 Oct;59:86-93. doi: 10.1016/j.jcrc.2020.05.008. Epub 2020 May 30.
PubMed 32585438
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Physical Therapy on NLRP3 Inflammasome Activation and Muscle Atrophy in Critical Illness Myopathy (PT-NLRP3-CIM).
- ClinicalTrials.gov ID
- NCT07017517
- Acronym / sponsor ID
- PT-NLRP3-CIM / 001-2025
- Conditions
- Critical Illness Myopathy
- Keywords
- Critical illness myopathy, Physical therapy, NALP3 inflammasome, Muscle atrophy, ICU-acquired weakness
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University of ChileUniversity, hospital or other
- Collaborators
- Clinica Indisa, Hospital de Urgencia y Asistencia Pública
- Study start
- 20 Apr 2026 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 12 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Critical illness myopathy (CIM) is a frequent complication in patients admitted to intensive care units (ICUs), characterized by symmetric proximal muscle weakness and respiratory muscle involvement. It has been linked to increased mortality, prolonged hospital stays, and long-term physical disability. CIM may also contribute to post-intensive care syndrome (PICS), which includes persistent cognitive, psychological, and physical impairments. In Chile, approximately 40% of patients with critical illness due to COVID-19 developed this syndrome.
Although several molecular mechanisms have been proposed, the precise etiopathogenesis of CIM remains unclear. Muscle atrophy and contractile dysfunction are hallmark features of CIM. The ubiquitin-proteasome system (UPS) and the upregulation of atrogenes such as MuRF1 and Atrogin-1 have been implicated in its development. In murine models of denervation and sepsis, the NLRP3 inflammasome-a multiprotein complex involved in innate immunity and IL-1β/IL-18 secretion-has been shown to promote muscle atrophy via activation of atrophy-related genes.
Evidence suggests that physical therapy can modulate inflammation at the skeletal muscle level, including downregulation of NLRP3 inflammasome components and IL-1β expression. Mechanical silencing, a major modifiable risk factor in CIM, can be mitigated by early mobilization strategies. However, it remains unknown whether physical therapy directly reduces NLRP3 inflammasome activation and associated muscle atrophy in patients with CIM.
This clinical trial is designed to test the hypothesis that physical therapy decreases NLRP3 inflammasome activity and reduces skeletal muscle atrophy in critically ill patients with CIM. In the early stage of ICU admission, sixteen patients at risk of CIM will be randomized to receive either conventional physical therapy or an enhanced protocol that includes servo-assisted motorized movement therapy (Motomed Letto®), twice daily for 60 minutes. In addition, eight patients without CIM will serve as non-CIM controls.
Muscle biopsy samples from the vastus lateralis will be analyzed to assess histological evidence of muscle atrophy, structural alterations in cellular organelles, and expression of atrophy-related genes. Quantitative real-time PCR (RT-qPCR) will be used to measure mRNA levels of atrogenes, and Western blot will assess protein expression of key mediators of NLRP3 inflammasome signaling. Transcriptomic analysis will be conducted using microarray profiling.
This study will address the following specific aims:
To evaluate the effect of physical therapy on NLRP3 inflammasome activation in skeletal muscle and compare it with non-CIM controls.
To assess the impact of physical therapy on muscle atrophy and explore its relationship with inflammasome activation.
To characterize the gene expression profile of signaling pathways involved in muscle degradation in CIM patients.
To analyze the association between molecular alterations in skeletal muscle and the clinical/ultrasound diagnosis of CIM.
It is expected that enhanced physical therapy will reduce NLRP3 inflammasome activity, attenuate muscle atrophy, and modify gene expression profiles involved in the progression of CIM. These molecular findings are anticipated to correlate with clinical assessments of muscle strength and ultrasound-based diagnosis, supporting the role of early mobilization as a non-pharmacological intervention in the management and prevention of CIM.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Enhanced or Additional Physical Therapy Group | Experimental | Device: Motomed Letto® servo-assisted cycling + standard physiotherapyCritically ill patients at risk of developing CIM will receive enhanced (additional) physical therapy consisting of standard physiotherapy plus servo-assisted lower-limb cycling using the Motomed Letto® device. Therapy will be delivered twice daily, 60 minutes per session, for 7 consecutive days during the early ICU stay. Muscle biopsies from the vastus lateralis will be collected for histological and molecular analyses. |
| Conventional Physical Therapy Group | Active comparator | Behavioral: Standard physiotherapyCritically ill patients at risk of CIM will receive standard physiotherapy delivered according to institutional ICU rehabilitation protocols. The intervention is delivered at the same frequency and clinical stage as the enhanced therapy group. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (16 listed)
- Neurocritical illness.
- Prior malnutrition or cachexia.
- Pre-existing neuromuscular disease.
- Coagulopathy (severe liver disease or continuous dialysis).
- Thrombocytopenia <20,000 platelets/μL.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Motomed Letto® servo-assisted cycling + standard physiotherapyAlso: Motomed Letto®, Additional Physical Therapy, Enhanced Physical TherapyServo-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). | Device | Enhanced or Additional Physical Therapy Group |
| Standard physiotherapyAlso: Conventional physical therapy, routine ICU physiotherapyStandard physiotherapy including mobilization and passive/active range-of-motion exercises, delivered during routine ICU care for 7 days. | Behavioural | Conventional Physical Therapy Group |
Primary outcome
Relative mRNA expression of NLRP3, IL-1β, and IL-18 in muscle tissue (RT-qPCR)
Time frame: Baseline and Day 7 (on the final day of intervention)
mRNA levels of NLRP3, IL-1β, and IL-18 will be quantified using RT-qPCR from muscle biopsy samples.
Protein expression of phospho-p65S536 and total p65 (Western blot)
Time frame: Baseline and Day 7 (on the final day of intervention)
Protein levels of phospho-p65 Serine 536 and total p65 will be assessed by Western blot to evaluate NF-κB pathway activation.
Ratio of cleaved/uncleaved caspase-1, IL-1β, and GSDMD-NT (Western blot)
Time frame: Baseline and Day 7 (on the final day of intervention)
Cleaved forms of IL-1β, caspase-1, and GSDMD-NT will be quantified by Western blot and normalized to precursor forms.
Plasma concentrations of IL-1β and IL-18 (ELISA)
Time frame: Baseline and Day 7 (on the final day of intervention)
Plasma levels of IL-1β and IL-18 will be measured using ELISA.
Expression of oxidative stress markers and cathepsin B (Western blot)
Time frame: Baseline and Day 7 (on the final day of intervention)
Protein carbonylation, nitration, and cathepsin B expression will be analyzed by Western blot.
Expression of cathepsin B (RT-qPCR)
Time frame: Baseline and Day 7 (on the final day of intervention)
Cathepsin B expression will be analyzed by RT-qPCR.
Ultrastructural mitochondrial damage and lysosomal vacuolization (TEM)
Time frame: Baseline and Day 7 (on the final day of intervention)
Mitochondrial damage and lysosomal vacuole volume will be assessed by transmission electron microscopy.
Muscle fiber diameter (immunofluorescence)
Time frame: Baseline and Day 7 (on the final day of intervention)
Fiber diameter in 10 µm cryosections will be measured using anti-laminin immunofluorescence.
mRNA expression of atrogenes: MuRF1, Atrogin-1, MUSA1, TRIM62, TRIM32
Time frame: Baseline and Day 7 (on the final day of intervention)
Atrogene mRNA levels will be quantified using RT-qPCR from muscle biopsies.
Myosin/actin ratio (Western blot)
Time frame: Baseline and Day 7 (on the final day of intervention)
Myosin and actin protein levels will be analyzed by Western blot to assess the molecular diagnosis of CIM.
Sarcomeric organization (TEM)
Time frame: Baseline and Day 7 (on the final day of intervention)
Evaluation of sarcomeric structure in cryosections using transmission electron microscopy.
2 secondary outcomes
Differential expression of genes related to atrophy and inflammasome activation (microarray or nanopore-based RNA sequencing )
Time frame: Baseline (prior to intervention) and Day 7 of intervention
Correlation between molecular findings and CIM clinical diagnosis
Time frame: From recovery of consciousness (in ICU or follow-up) through 90-day follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Background: PubMed 34638553Americo-Da-Silva L, Aguilera J, Quinteros-Waltemath O, Sanchez-Aguilera P, Russell J, Cadagan C, Meneses-Valdes R, Sanchez G, Estrada M, Jorquera G, Barrientos G, Llanos P. Activation of the NLRP3 Inflammasome Increases the IL-1beta Level and Decreases GLUT4 Translocation in Skeletal Muscle during Insulin Resistance. Int J Mol Sci. 2021 Sep 23;22(19):10212. doi: 10.3390/ijms221910212.
- Background: PubMed 21392121Neves M Jr, Barreto G, Boobis L, Harris R, Roschel H, Tricoli V, Ugrinowitsch C, Negrao C, Gualano B. Incidence of adverse events associated with percutaneous muscular biopsy among healthy and diseased subjects. Scand J Med Sci Sports. 2012 Apr;22(2):175-8. doi: 10.1111/j.1600-0838.2010.01264.x. Epub 2011 Mar 10.
- Background: PubMed 32519182Raithatha A, Ashraghi MR, Lord C, Limback-Stanic C, Viegas S, Amiras D. Ultrasound-guided muscle biopsy: a practical alternative for investigation of myopathy. Skeletal Radiol. 2020 Nov;49(11):1855-1859. doi: 10.1007/s00256-020-03484-y. Epub 2020 Jun 9.
- Background: PubMed 27059469Kho ME, Molloy AJ, Clarke F, Herridge MS, Koo KK, Rudkowski J, Seely AJ, Pellizzari JR, Tarride JE, Mourtzakis M, Karachi T, Cook DJ; Canadian Critical Care Trials Group. CYCLE pilot: a protocol for a pilot randomised study of early cycle ergometry versus routine physiotherapy in mechanically ventilated patients. BMJ Open. 2016 Apr 8;6(4):e011659. doi: 10.1136/bmjopen-2016-011659.
- Background: PubMed 38888743Moisi L, Mino JC, Guidet B, Vallet H. Frailty assessment in critically ill older adults: a narrative review. Ann Intensive Care. 2024 Jun 18;14(1):93. doi: 10.1186/s13613-024-01315-0.
- Background: PubMed 15161965Mahoney DJ, Carey K, Fu MH, Snow R, Cameron-Smith D, Parise G, Tarnopolsky MA. Real-time RT-PCR analysis of housekeeping genes in human skeletal muscle following acute exercise. Physiol Genomics. 2004 Jul 8;18(2):226-31. doi: 10.1152/physiolgenomics.00067.2004.
- Background: PubMed 32316800Gonzalez-Seguel F, Camus-Molina A, Carcamo M, Hiser S, Needham DM, Leppe J. Inter-observer reliability of trained physiotherapists on the Functional Status Score for the Intensive Care Unit Chilean-Spanish version. Physiother Theory Pract. 2022 Feb;38(2):365-371. doi: 10.1080/09593985.2020.1753272. Epub 2020 Apr 22.
- Background: PubMed 30591032Pardo E, El Behi H, Boizeau P, Verdonk F, Alberti C, Lescot T. Reliability of ultrasound measurements of quadriceps muscle thickness in critically ill patients. BMC Anesthesiol. 2018 Dec 27;18(1):205. doi: 10.1186/s12871-018-0647-9.
- Background: PubMed 28808365Hadda V, Khilnani GC, Kumar R, Dhunguna A, Mittal S, Khan MA, Madan K, Mohan A, Guleria R. Intra- and Inter-observer Reliability of Quadriceps Muscle Thickness Measured with Bedside Ultrasonography by Critical Care Physicians. Indian J Crit Care Med. 2017 Jul;21(7):448-452. doi: 10.4103/ijccm.IJCCM_426_16.
- Background: PubMed 32948221Turan Z, Topaloglu M, Ozyemisci Taskiran O. Medical Research Council-sumscore: a tool for evaluating muscle weakness in patients with post-intensive care syndrome. Crit Care. 2020 Sep 18;24(1):562. doi: 10.1186/s13054-020-03282-x. No abstract available.
- Background: PubMed 23900509Pietrangelo T, Perni S, Di Tano G, Fano-Illic G, Franzini-Armstrong C. A method for the ultrastructural preservation of tiny percutaneous needle biopsy material from skeletal muscle. Int J Mol Med. 2013 Oct;32(4):965-70. doi: 10.3892/ijmm.2013.1454. Epub 2013 Jul 23.
- Background: PubMed 25475522Hodgson CL, Stiller K, Needham DM, Tipping CJ, Harrold M, Baldwin CE, Bradley S, Berney S, Caruana LR, Elliott D, Green M, Haines K, Higgins AM, Kaukonen KM, Leditschke IA, Nickels MR, Paratz J, Patman S, Skinner EH, Young PJ, Zanni JM, Denehy L, Webb SA. Expert consensus and recommendations on safety criteria for active mobilization of mechanically ventilated critically ill adults. Crit Care. 2014 Dec 4;18(6):658. doi: 10.1186/s13054-014-0658-y.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be shared in order to uphold ethical standards of patient confidentiality. All data collected will be treated in strict compliance with ethical and regulatory guidelines to protect participant identity. The dissemination of results will occur exclusively in aggregate form, fully anonymized, and only in scientific or academic settings, such as peer-reviewed publications or presentations at conferences.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paola A Llanos, PhD study director
University of Chile
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Motomed Letto® servo-assisted cycling + standard physiotherapy and Standard physiotherapy in people with Critical Illness Myopathy, run by University of Chile at 3 sites in Chile.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Chile. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Óscar L Arellano-Pérez, MSc. (+56961479414, oscar.arellano@ug.uchile.cl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative mRNA expression of NLRP3, IL-1β, and IL-18 in muscle tissue (RT-qPCR) (time frame: Baseline and Day 7 (on the final day of intervention)). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07017517, which also lists 104 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026; AzTrials last refreshed its copy on 7 Nov 2026.