Critical Illness Weakness Outside the Intensive Care Unit.

NCT07478367 | Recruiting

• 1 other identifier: 681/25
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief 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. 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.

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

Outcome Measures

Primary Outcomes (1)

• Incidence of CRIMYNE-like neuromuscular involvement

  Presence of new-onset weakness (yes/no)

  At hospital discharge

Secondary Outcomes (1)

• Electrophysiological evidence of CRIMYNE-like neuromuscular involvement

  At hospital discharge

Study Arms (2)

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.

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.

Other: No Intervention: Observational Cohort

Interventions

No Intervention: Observational Cohort OTHER

No intervention is administered.

Also known as: No intervention (observational study)

control group; study group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead

Study Sites (1)

Humanitas Research Institute

Rozzano, 20096, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples collected during routine clinical blood draws in a subgroup of patients who develop new-onset muscle weakness during hospitalization. Up to three additional blood tubes per patient will be stored for the analysis of inflammatory biomarkers and markers of peripheral nerve/axonal damage (including neurofilament light chain). No other biological samples will be retained.

MeSH Terms

Conditions

Polyneuropathies; Muscular Diseases

Interventions

Observation

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Pietro E Doneddu

  Humanitas Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pietro E Doneddu, MD

CONTACT

+39 0282247761; pietro.doneddu@hunimed.eu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2026
• First Posted: March 17, 2026
• Study Start: November 18, 2025
• Primary Completion (Estimated): October 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)