Long-Term Outcomes and Post-Intensive Care Syndrome: Investigating the Associations Between Metabolic Signatures and Physical Functioning in Critically Ill Patients

NCT07170527 | Recruiting DMC

• 1 other identifier: NL87540.091.24
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Despite being young, healthy, and physically fit, some intensive care unit (ICU) patients experience significantly worse functional recovery after critical illness than older patients with multiple comorbidities although a poor precondition seems to be associated with worse ICU outcomes. This paradox highlights a fundamental gap in our understanding of the determinants of long-term recovery. While nonmodifiable factors such as age and pre-existing disease explain part of the variation, they cannot fully account for the wide heterogeneity in outcomes. Metabolic disturbances during critical illness, such as hypercatabolism, impaired muscle metabolism, nutritional deficits, systemic inflammation, and disruption of gut health, are likely to influence recovery trajectories, yet remain poorly characterized. Because these processes represent potentially modifiable targets, combining their evaluation with nonmodifiable patient characteristics is essential for unraveling the complex, multifactorial mechanisms underlying post-intensive care syndrome (PICS). This explorative, prospective, observational study aims to investigate the associations between metabolic signatures during the acute phase of critical illness and PICS outcomes throughout the recovery trajectory of ICU survivors, with a primary focus on physical functioning. In addition, the study explores the longitudinal course of metabolic parameters from ICU admission up to 12 months post-discharge, and whether these signatures can help identify distinct recovery phenotypes. Participants will be followed for 12 months, with study assessments at ICU admission, ICU discharge, and at 3-, 6-, and 12-months post-ICU admission.

Conditions

Post-Intensive Care Syndrome (PICS)

Keywords

Post-Intensive Care Syndrome (PICS); Critical illness; Intensive Care Unit (ICU); Recovery; Long-Term Outcomes

Outcome Measures

Primary Outcomes (6)

• Subjective physical functioning

  Assessed by the Physical Component Score (PCS) of the Short Form-36 (SF-36) questionnaire, ranging from 0 to 100. Scores above or below the average of 50 indicate better or worse physical health compared to the general population, respectively.

  3-months post-ICU admission

• Handgrip strength

  Assessed with Jamar dynamometer, measured in kilograms (kg).

  3-months post-ICU admission

• Leg strength and endurance

  Assessed by the 30-second chair stand test (30sCST)

  3-months post-ICU admission

• Muscle size

  Assessed by muscle ultrasound of the quadriceps muscles

  3-months post-ICU admission

• Muscle size

  Assessed by calf circumference, measured in cm

  3-months post-ICU admission

• Body composition

  Assessed by bio-electrical impedance analysis (BIA)

  3-months post-ICU admission

Secondary Outcomes (39)

• Subjective physical functioning

  3 times during cohort (at ICU discharge (an average of 10 days), 6- and 12-months post-ICU admission)

• Handgrip strength

  3 times during cohort (at ICU discharge (an average of 10 days), 6- and 12-months post-ICU admission)

• Leg strength and endurance

  3 times during cohort (at ICU discharge (an average of 10 days), 6- and 12-months post-ICU admission)

• Muscle size

  4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 6- and 12-months post-ICU admission)

• Muscle size

  4 times during cohort (at ICU admission, at ICU discharge (an average of 10 days), 6- and 12-months post-ICU admission)

Study Arms (1)

Cohort

Adult patients with an expected ICU length of stay of ≥72 hours, or who receive (non-) invasive mechanical ventilation (IMV or NIV) within 48 hours after ICU admission with an expected ventilatory support duration of at least 48 hours.

Eligibility Criteria

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

Study Population

The study population will consist of 200 adult patients admitted to the ICU of Gelderse Vallei Hospital, Ede, with an expected ICU length of stay of ≥72 hours, or who receive invasive mechanical ventilation (IMV) or non-invasive ventilation (NIV) within 48 hours after ICU admission and are expected to receive this ventilatory support (IMV or NIV) for ≥48 hours.

You may qualify if:

• Age ≥ 18 years at time of ICU admission;
• Received ventilatory support (IMV or NIV) within 48 hours after ICU admission with an expected duration of ≥48 hours during ICU stay (irrespective of ICU length of stay); OR
• An expected ICU length of stay of ≥72 hours (irrespective of ventilatory support).

You may not qualify if:

• Concurrent participation in an intervention study with an anticipated therapeutic effect on PICS outcomes (physical functioning, cognitive functioning, or mental health status)
• Pre-admission diagnosis of a progressive neurological disease (e.g., Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, progressive forms of multiple sclerosis)
• Participants with neurological paralysis significantly affecting leg function (e.g., spinal cord injury, multiple sclerosis)
• Patients receiving palliative care, with a life expectancy of \<3 months (e.g., hospice care or equivalent)
• Patients who are moribund (i.e., in the final stages of a terminal illness, with imminent death expected)
• Anticipated logistical limitations during recovery phase (e.g., transfer to another hospital, no fixed abode);
• Deemed not suitable to participate based upon the judgement of the treating intensivist.

Sponsors & Collaborators

• ARH van Zanten, MD PhD: lead
• Danone Global Research & Innovation Center: collaborator
• Wageningen University and Research: collaborator
• TKI Agri & Food: collaborator

Study Sites (1)

Gelderse Vallei Hospital

Ede, Gelderland, 6716 RP, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, serum, whole blood, feces

MeSH Terms

Conditions

postintensive care syndrome; Critical Illness

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Arthur HR van Zanten, MD, PhD

CONTACT

+31318435964; zantena@zgv.nl

Noortje MP Overwater, MSc

CONTACT

+31318434119; noverwater@zgv.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: August 30, 2025
• First Posted: September 12, 2025
• Study Start: October 13, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: February 12, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

NL (1)