Critical Illness PolyneuromyopathyCRI-WEAK-OUTNCT07478367
Critical Illness Weakness Outside the Intensive Care Unit.
An observational study of Critical Illness Polyneuromyopathy and Critical Illness Polyneuropathy, run by Istituto Clinico Humanitas at 1 site in Italy.
Trial summary
When people become seriously ill, their bodies can be affected in many ways beyond the original disease. One well-known complication in patients treated in intensive care units (ICUs) is the development of severe muscle weakness caused by damage to muscles and nerves. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Critical Illness Polyneuromyopathy, Critical Illness Polyneuropathy, Critical Illness Myopathy
- How many people
- 300 participants
- Where
- 1 siteItaly
- Study dates
- 18 Nov 2025to 30 Nov 2028
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Adult patients hospitalized for acute illness in non-ICU medical wards. Participants are classified into cohorts based on the presence or absence of organ failure during hospitalization, defined by the Sequential Organ Failure Assessment (SOFA) score.
Who may be able to join
- Age ≥ 18 years
- Hospitalization for acute illness in a non-ICU unit
- For the critical illness cohort: presence of organ failure defined as a SOFA score ≥ 2 at admission or an increase (ΔSOFA) ≥ 2 during hospitalization
- For the control cohort: SOFA score < 2 throughout hospitalization
- Ability to provide written informed consent
Who cannot join
- History of peripheral neuropathy, myopathy, or other neuromuscular disorders (e.g., myasthenia gravis)
- Conditions affecting the lower limbs that prevent electrophysiological testing
- Delirium with agitation preventing clinical evaluation
- Coma or inability to assess muscle strength
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Humanitas Research Institute
Rozzano, 20096
Pietro E Doneddu, MD, +39 0282247761, pietro.doneddu@hunimed.eu
About this study
Official title: Critical Illness Weakness Outside the Intensive Care Unit. A Prospective Cohort Study.
When people become seriously ill, their bodies can be affected in many ways beyond the original disease. One well-known complication in patients treated in intensive care units (ICUs) is the development of severe muscle weakness caused by damage to muscles and nerves. This condition is called critical illness-related weakness and includes disorders of the nerves (neuropathy), the muscles (myopathy), or both. These problems can make it difficult for patients to move, walk, or even breathe independently, and recovery can take months or longer.
So far, most research on this type of weakness has focused on patients who were treated in ICUs. However, many hospitalized patients outside the ICU-such as those admitted to internal medicine wards or semi-intensive care units-can also experience severe infections, organ failure, inflammation, prolonged bed rest, and metabolic stress. These are the same risk factors known to cause nerve and muscle damage in ICU patients. Despite this, weakness occurring outside the ICU is often overlooked, attributed simply to "deconditioning" or prolonged bed rest, and not properly investigated.
Read more
The CRI-WEAK-OUT study aims to better understand whether critical illness-related weakness also occurs in hospitalized patients who are not admitted to the ICU, how often it happens, how severe it is, and what factors increase the risk of developing it.
This is a prospective observational study, meaning that patients will be followed over time during and after their hospital stay, without changing their usual medical care. The study will include about 600 adult patients hospitalized for acute illnesses in non-ICU wards across several Italian hospitals. Half of the participants will have signs of organ failure during hospitalization, while the other half will serve as a comparison group without organ failure.
All participants will undergo careful clinical evaluations shortly after hospital admission and again before discharge. Doctors will assess muscle strength, level of disability, independence in daily activities, and overall frailty using standardized and widely accepted scales. Six months after discharge, patients will be contacted by phone to evaluate their recovery and quality of life.
If a patient develops new or worsening muscle weakness during hospitalization, more detailed tests will be performed. These include electrical tests of nerves and muscles to understand whether the weakness is caused mainly by nerve damage, muscle damage, or both. In a subgroup of patients, additional blood samples will be collected to measure substances linked to inflammation and nerve injury. These biological markers may help doctors recognize the condition earlier and predict recovery.
By collecting detailed clinical, electrical, and biological information, the study aims to answer several important questions:
- How common is critical illness-related weakness outside the ICU?
- Which patients are most at risk?
- How does this condition affect recovery and long-term independence?
- Can blood markers help identify patients with nerve or muscle damage? The results of the CRI-WEAK-OUT study may improve awareness of this under-recognized condition, promote earlier diagnosis, and help clinicians plan better prevention and rehabilitation strategies. Ultimately, this research could lead to improved care, faster recovery, and better quality of life for many hospitalized patients who currently experience unexplained weakness after acute illness.
Read the detailed description
Critical illness myopathy and neuropathy (CRIMYNE) is a spectrum of neuromuscular disorders that develop in patients with severe systemic illness and includes critical illness polyneuropathy, critical illness myopathy, and overlapping forms. These conditions are characterized by generalized symmetrical weakness involving limb and respiratory muscles and typically emerge during or after a prolonged critical illness. CRIMYNE is associated with prolonged mechanical ventilation, extended hospital stays, increased mortality, and long-term disability.
Although CRIMYNE has been primarily described in patients admitted to intensive care units (ICUs), many of the risk factors associated with its development-including systemic inflammation, sepsis, metabolic disturbances, hyperglycemia, prolonged immobilization, and multiorgan dysfunction-are also present in patients hospitalized in internal medicine wards or semi-intensive care settings. Despite this overlap, neuromuscular weakness related to acute illness in non-ICU patients remains poorly recognized and is often attributed to nonspecific causes such as general deconditioning or prolonged bed rest.
It is plausible that neuromuscular involvement similar to CRIMYNE may occur outside the ICU in patients experiencing acute illness with systemic stress and organ dysfunction. However, this condition may be underdiagnosed in non-ICU environments due to limited awareness, competing clinical priorities, and potentially milder clinical manifestations. A better understanding of the occurrence, clinical characteristics, and outcomes of CRIMYNE-like neuromuscular involvement in non-ICU hospitalized patients could improve recognition of this condition, facilitate earlier diagnosis, and support the development of preventive and rehabilitation strategies.
This study is a prospective cohort study including hospitalized adult patients admitted to non-ICU hospital units for acute medical conditions. Participants will be evaluated during hospitalization and followed longitudinally to investigate the occurrence of neuromuscular weakness compatible with CRIMYNE-like involvement.
Participants will undergo clinical evaluation at baseline, within 48 hours of hospital admission, and again near the time of discharge. Muscle strength, disability, and frailty will be assessed using standardized clinical scales. A follow-up evaluation will be performed six months after hospital discharge to assess functional outcomes and quality of life.
Patients who develop clinically significant muscle weakness during hospitalization will undergo electrophysiological evaluation to characterize possible neuromuscular involvement. Additional clinical data, laboratory values, comorbidities, and treatments during hospitalization will be collected from medical records to identify potential risk factors associated with the development of neuromuscular weakness.
In a subgroup of patients, blood samples will be collected to investigate biomarkers associated with peripheral nerve and muscle injury as well as systemic inflammation. These analyses will include measurement of neurofilament light chain and selected inflammatory markers. The aim of this exploratory component is to evaluate whether circulating biomarkers are associated with the development of neuromuscular involvement and with clinical outcomes.
By investigating the occurrence and characteristics of CRIMYNE-like neuromuscular involvement in patients hospitalized outside the ICU, this study aims to improve understanding of this potentially underrecognized complication of acute illness. The results may help identify patients at risk, support earlier recognition of neuromuscular weakness during hospitalization, and inform future preventive and therapeutic strategies.
- Conditions
- Critical Illness Polyneuromyopathy, Critical Illness Polyneuropathy, Critical Illness Myopathy
- Being tested
- No Intervention: Observational Cohort
- Keywords
- critical illness neuropathy, critical illness myopathy, critical illness weakness, Non-ICU hospitalized patients, polyneuropathy, myopathy, Organ failure
- Medical subject headings
- Polyneuropathies, Muscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No Intervention: Observational CohortOther
Also called No intervention (observational study)
No intervention is administered.
| Study group | Role | What they receive |
|---|---|---|
| study group | Hospitalized non-ICU patients with acute illness and organ failure, defined as a SOFA score ≥ 2 or an increase (ΔSOFA) ≥ 2 during hospitalization. Receives: Other: No Intervention: Observational Cohort | |
| control group | Hospitalized non-ICU patients with acute illness without organ failure, defined as a SOFA score < 2 throughout hospitalization. Receives: Other: No Intervention: Observational Cohort |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of CRIMYNE-like neuromuscular involvement
Presence of new-onset weakness (yes/no)
Measured: At hospital discharge
Secondary outcomes (1)
Electrophysiological evidence of CRIMYNE-like neuromuscular involvement
Presence of electrophysiological findings consistent with critical illness-related polyneuropathy and/or myopathy on nerve conduction studies and needle electromyography in patients who develop muscle weakness during hospitalization.
Measured: At hospital discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2026
- Study start18 Nov 2025
- Primary completion30 Oct 2028 (estimated)
- Study completion30 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical Illness PolyneuromyopathyStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pietro E Doneddu, Principal investigator, Humanitas Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07478367
- Sponsor's protocol ID
- 681/25
- Acronym
- CRI-WEAK-OUT
- Status last verified
- Mar 2026
- First submitted
- 20 Jan 2026
- Last updated
- 17 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Critical Illness Weakness Outside the Intensive Care Unit. A Prospective Cohort Study.
- ClinicalTrials.gov ID
- NCT07478367
- Acronym / sponsor ID
- CRI-WEAK-OUT / 681/25
- Conditions
- Critical Illness Polyneuromyopathy, Critical Illness Polyneuropathy, Critical Illness Myopathy
- Keywords
- critical illness neuropathy, critical illness myopathy, critical illness weakness, Non-ICU hospitalized patients, polyneuropathy, myopathy, Organ failure
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Study start
- 18 Nov 2025 (actual)
- Primary completion
- 30 Oct 2028 (estimated)
- Study completion
- 30 Nov 2028 (estimated)
- First posted
- 17 Mar 2026 (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.
When people become seriously ill, their bodies can be affected in many ways beyond the original disease. One well-known complication in patients treated in intensive care units (ICUs) is the development of severe muscle weakness caused by damage to muscles and nerves. This condition is called critical illness-related weakness and includes disorders of the nerves (neuropathy), the muscles (myopathy), or both. These problems can make it difficult for patients to move, walk, or even breathe independently, and recovery can take months or longer.
So far, most research on this type of weakness has focused on patients who were treated in ICUs. However, many hospitalized patients outside the ICU-such as those admitted to internal medicine wards or semi-intensive care units-can also experience severe infections, organ failure, inflammation, prolonged bed rest, and metabolic stress. These are the same risk factors known to cause nerve and muscle damage in ICU patients. Despite this, weakness occurring outside the ICU is often overlooked, attributed simply to "deconditioning" or prolonged bed rest, and not properly investigated.
The CRI-WEAK-OUT study aims to better understand whether critical illness-related weakness also occurs in hospitalized patients who are not admitted to the ICU, how often it happens, how severe it is, and what factors increase the risk of developing it.
This is a prospective observational study, meaning that patients will be followed over time during and after their hospital stay, without changing their usual medical care. The study will include about 600 adult patients hospitalized for acute illnesses in non-ICU wards across several Italian hospitals. Half of the participants will have signs of organ failure during hospitalization, while the other half will serve as a comparison group without organ failure.
All participants will undergo careful clinical evaluations shortly after hospital admission and again before discharge. Doctors will assess muscle strength, level of disability, independence in daily activities, and overall frailty using standardized and widely accepted scales. Six months after discharge, patients will be contacted by phone to evaluate their recovery and quality of life.
If a patient develops new or worsening muscle weakness during hospitalization, more detailed tests will be performed. These include electrical tests of nerves and muscles to understand whether the weakness is caused mainly by nerve damage, muscle damage, or both. In a subgroup of patients, additional blood samples will be collected to measure substances linked to inflammation and nerve injury. These biological markers may help doctors recognize the condition earlier and predict recovery.
By collecting detailed clinical, electrical, and biological information, the study aims to answer several important questions:
- How common is critical illness-related weakness outside the ICU?
- Which patients are most at risk?
- How does this condition affect recovery and long-term independence?
- Can blood markers help identify patients with nerve or muscle damage? The results of the CRI-WEAK-OUT study may improve awareness of this under-recognized condition, promote earlier diagnosis, and help clinicians plan better prevention and rehabilitation strategies. Ultimately, this research could lead to improved care, faster recovery, and better quality of life for many hospitalized patients who currently experience unexplained weakness after acute illness.
Detailed description
Critical illness myopathy and neuropathy (CRIMYNE) is a spectrum of neuromuscular disorders that develop in patients with severe systemic illness and includes critical illness polyneuropathy, critical illness myopathy, and overlapping forms. These conditions are characterized by generalized symmetrical weakness involving limb and respiratory muscles and typically emerge during or after a prolonged critical illness. CRIMYNE is associated with prolonged mechanical ventilation, extended hospital stays, increased mortality, and long-term disability.
Although CRIMYNE has been primarily described in patients admitted to intensive care units (ICUs), many of the risk factors associated with its development-including systemic inflammation, sepsis, metabolic disturbances, hyperglycemia, prolonged immobilization, and multiorgan dysfunction-are also present in patients hospitalized in internal medicine wards or semi-intensive care settings. Despite this overlap, neuromuscular weakness related to acute illness in non-ICU patients remains poorly recognized and is often attributed to nonspecific causes such as general deconditioning or prolonged bed rest.
It is plausible that neuromuscular involvement similar to CRIMYNE may occur outside the ICU in patients experiencing acute illness with systemic stress and organ dysfunction. However, this condition may be underdiagnosed in non-ICU environments due to limited awareness, competing clinical priorities, and potentially milder clinical manifestations. A better understanding of the occurrence, clinical characteristics, and outcomes of CRIMYNE-like neuromuscular involvement in non-ICU hospitalized patients could improve recognition of this condition, facilitate earlier diagnosis, and support the development of preventive and rehabilitation strategies.
This study is a prospective cohort study including hospitalized adult patients admitted to non-ICU hospital units for acute medical conditions. Participants will be evaluated during hospitalization and followed longitudinally to investigate the occurrence of neuromuscular weakness compatible with CRIMYNE-like involvement.
Participants will undergo clinical evaluation at baseline, within 48 hours of hospital admission, and again near the time of discharge. Muscle strength, disability, and frailty will be assessed using standardized clinical scales. A follow-up evaluation will be performed six months after hospital discharge to assess functional outcomes and quality of life.
Patients who develop clinically significant muscle weakness during hospitalization will undergo electrophysiological evaluation to characterize possible neuromuscular involvement. Additional clinical data, laboratory values, comorbidities, and treatments during hospitalization will be collected from medical records to identify potential risk factors associated with the development of neuromuscular weakness.
In a subgroup of patients, blood samples will be collected to investigate biomarkers associated with peripheral nerve and muscle injury as well as systemic inflammation. These analyses will include measurement of neurofilament light chain and selected inflammatory markers. The aim of this exploratory component is to evaluate whether circulating biomarkers are associated with the development of neuromuscular involvement and with clinical outcomes.
By investigating the occurrence and characteristics of CRIMYNE-like neuromuscular involvement in patients hospitalized outside the ICU, this study aims to improve understanding of this potentially underrecognized complication of acute illness. The results may help identify patients at risk, support earlier recognition of neuromuscular weakness during hospitalization, and inform future preventive and therapeutic strategies.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| study group | – | Other: No Intervention: Observational CohortHospitalized non-ICU patients with acute illness and organ failure, defined as a SOFA score ≥ 2 or an increase (ΔSOFA) ≥ 2 during hospitalization. |
| control group | – | Other: No Intervention: Observational CohortHospitalized non-ICU patients with acute illness without organ failure, defined as a SOFA score < 2 throughout hospitalization. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Adult patients hospitalized for acute illness in non-ICU medical wards. Participants are classified into cohorts based on the presence or absence of organ failure during hospitalization, defined by the Sequential Organ Failure Assessment (SOFA) score.
Key inclusion criteria (5 listed)
- Age ≥ 18 years
- Hospitalization for acute illness in a non-ICU unit
- For the critical illness cohort: presence of organ failure defined as a SOFA score ≥ 2 at admission or an increase (ΔSOFA) ≥ 2 during hospitalization
- For the control cohort: SOFA score < 2 throughout hospitalization
- Ability to provide written informed consent
Key exclusion criteria (4 listed)
- History of peripheral neuropathy, myopathy, or other neuromuscular disorders (e.g., myasthenia gravis)
- Conditions affecting the lower limbs that prevent electrophysiological testing
- Delirium with agitation preventing clinical evaluation
- Coma or inability to assess muscle strength
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 |
|---|---|---|
| No Intervention: Observational CohortAlso: No intervention (observational study)No intervention is administered. | Other | control group, study group |
Primary outcome
Incidence of CRIMYNE-like neuromuscular involvement
Time frame: At hospital discharge
Presence of new-onset weakness (yes/no)
1 secondary outcome
Electrophysiological evidence of CRIMYNE-like neuromuscular involvement
Time frame: At hospital discharge
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 17 Mar 2026.
- Individual participant dataSharing planned: No
Related trials for Critical Illness Polyneuromyopathy
Recruiting
High-Tech Rehabilitation Pathway for Acute Adult Neuromuscular Diseases - Fit4MedRob-Acute MND Project
Critical Illness Myopathy, Guillain Barré Syndrome
Active, not recruitingObservational study
CPAx: Responsiveness and Minimal Clinically Important Difference
Muscle Weakness, Critical Illness Myopathy
RecruitingObservational study
Recovery From ICUAW Following Severe Respiratory and Cardiac Failure
Intensive Care Unit Syndrome, Intensive Care Neuropathy
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.
Pietro E Doneddu principal investigator
Humanitas Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Critical Illness Polyneuromyopathy and Critical Illness Polyneuropathy, run by Istituto Clinico Humanitas at 1 site in Italy.
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 5 inclusion and 4 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 17 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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 Pietro E Doneddu, MD (+39 0282247761, pietro.doneddu@hunimed.eu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of CRIMYNE-like neuromuscular involvement (time frame: At hospital discharge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Mar 2026.