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Diaphragm Hibernation and Its Driving Factors in Mechanically Ventilated ICU Patients (DISSECT)

14. september 2026 opdateret af: Radboud University Medical Center

Diaphragm hIbernation and itS Driving factorS in mEChanically venTilated ICU Patients: the DISSECT Study

Rationale:

Patients with invasive mechanical ventilation (IMV) frequently develop diaphragm dysfunction and experience difficult weaning. Recent ex vivo work suggests that a subset of mechanically ventilated ICU patients may exhibit diaphragm hibernation, an energy conserving myosin state that reduces force generation and may lead to a reversible increase in diaphragm strength over time. However, it is unknown whether diaphragm hibernation can be demonstrated in vivo during IMV and which clinical and biological factors are associated with this phenotype.

Objective:

Primary objective is to determine the driving factors (biomarkers) of diaphragm hibernation during IMV. Secondary objectives are to determine the proportion of ventilated critically ill patients who exhibit diaphragm hibernation during IMV, to investigate inflammatory and metabolic factors and other clinical exposures associated with diaphragm hibernation, and to explore associations between diaphragm hibernation and weaning related and survival outcomes.

Study design:

Prospective, observational, longitudinal cohort study.

Study population:

Adult ICU patients receiving IMV, expected to remain mechanically ventilated for at least 72 hours.

Intervention (if applicable):

Not applicable. This is an observational study. Study specific procedures consist of repeated phrenic nerve magnetic stimulation and additional blood sampling.

Main study parameters/endpoints:

The primary study parameter is the proportion of participants exhibiting diaphragm hibernation during IMV. Diaphragm hibernation is defined as an increase in stimulated twitch tracheal pressure (Ptr,stim), a measure of diaphragm strength, of at least 10% relative to baseline (Day 0-1) at any follow up assessment (Day 2, 3, 5, or 7) obtained before extubation or death. Ptr,stim will be assessed repeatedly on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Participant burden is limited and mainly consists of repeated phrenic nerve magnetic stimulation during a ventilator delivered end expiratory occlusion and additional blood sampling of 9.5 mL per time point, up to a total of 47.5 mL across the study period. Magnetic stimulation is non-invasive and expected discomfort is transient. Rare transient physiological changes may occur and measurements are performed under continuous ICU monitoring and will be postponed or omitted if considered unsafe or interfering with clinical care. Direct benefit for participants is limited, but the study may provide clinically relevant knowledge on diaphragm hibernation and its driving factors. The research questions are specific to diaphragm physiology during IMV in critically ill patients, therefore the study is group related and cannot be performed in a different population.

Studieoversigt

Status

Ikke rekrutterer endnu

Betingelser

Undersøgelsestype

Observationel

Tilmelding (Anslået)

112

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

  • Holland
    • Gelderland
      • Nijmegen, Gelderland, Holland, 6525 GA
        • Radboud University Medical Center (Radboudumc)
        • Kontakt:

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Prøveudtagningsmetode

Ikke-sandsynlighedsprøve

Studiebefolkning

The study population consists of newly admitted adult ICU patients receiving invasive mechanical ventilation, in whom the first study assessment can be performed within 36 hours after initiation of IMV and who are expected to require IMV for at least 3 days.

Beskrivelse

Inclusion Criteria:

  • Age ≥ 18 years.
  • Receiving invasive mechanical ventilation at screening.
  • Expected to remain mechanically ventilated for ≥ 72 hours from enrolment.
  • The first study assessment can be performed within 36 hours after initiation of invasive mechanical ventilation.

Exclusion Criteria:

  • Pre-existing neuromuscular disease affecting the diaphragm (e.g. motor neuron disease, myasthenia gravis, advanced muscular dystrophy, high cervical spinal cord injury) or use of neuromuscular blocker.
  • Known phrenic nerve palsy or prior diaphragmatic paralysis.
  • Long-term home mechanical ventilation (invasive or non-invasive) prior to ICU admission.
  • Post-operative patients after planned diaphragm or phrenic nerve surgery.
  • Contraindications to phrenic nerve magnetic stimulation (e.g., unstable cervical spine injury, uncontrolled intracranial hypertension, metallic implants in stimulation area as per manufacturer guidance).
  • Pregnancy.
  • Participation in another interventional trial that explicitly prohibits co-enrolment or is expected to substantially influence diaphragm function (e.g. experimental neuromuscular blocking strategies), as decided by the principal investigator.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

Kohorter og interventioner

Gruppe / kohorte
Patients with expected > 3 days of invasive mechanical ventilation
Patients expected > 3 days of invasive mechanical ventilation will be included in this study. Blood sample and diaphragm strength will be assessed repeatedly, until 7 days after initiation of invasive mechanical ventilation, extubation or death.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Blood C reactive protein level
Tidsramme: C reactive protein will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
C reactive protein will be assessed by blood sample.
C reactive protein will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Blood procalcitonin level
Tidsramme: Procalcitonin will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Procalcitonin will be assessed by blood sample.
Procalcitonin will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Blood metabolic biomarkers level
Tidsramme: Metabolic biomarkers will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Metabolic biomarkers will be assessed by blood sample using OLINK Target 96 panel.
Metabolic biomarkers will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Blood TNF-α level
Tidsramme: TNF-α will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
TNF-α will be assessed by blood sample.
TNF-α will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Blood IL-10 level
Tidsramme: IL-10 will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
IL-10 will be assessed by blood sample.
IL-10 will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Blood IL-8 level
Tidsramme: IL-8 will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
IL-8 will be assessed by blood sample.
IL-8 will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Blood IL-6 level
Tidsramme: IL-6 will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
IL-6 will be assessed by blood sample.
IL-6 will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Blood ferritin level
Tidsramme: Ferritin will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Ferritin will be assessed by blood sample.
Ferritin will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Proportion of participants exhibiting diaphragm hibernation during invasive mechanical ventilation
Tidsramme: Ptr,stim will be assessed repeatedly on Day 0 to 1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Diaphragm hibernation is defined as an increase in stimulated twitch tracheal pressure (Ptr,stim), a measure of diaphragm strength, of at least 10% relative to baseline (Day 0 to 1) at any follow up assessment (Day 2, 3, 5, or 7) obtained before extubation or death.
Ptr,stim will be assessed repeatedly on Day 0 to 1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Number of days from intubation to successful extubation
Tidsramme: Collected from study inclusion until Day 28, or ICU/hospital discharge or death, whichever occurs first
Data about number of days from intubation to successful extubation will be retrieved from electronic medical records.
Collected from study inclusion until Day 28, or ICU/hospital discharge or death, whichever occurs first
Number of days from first SBT to successful extubation
Tidsramme: Collected from study inclusion until Day 28, or ICU/hospital discharge or death, whichever occurs first
Data about number of days from first SBT to successful extubation will be retrieved from electronic medical records.
Collected from study inclusion until Day 28, or ICU/hospital discharge or death, whichever occurs first
Incidence of weaning failure
Tidsramme: Collected from study inclusion until Day 28, or ICU/hospital discharge or death, whichever occurs first
Weaning failure is defined as SBT failure or reintubation within 48 hours. Data will be retrieved from electronic medical records.
Collected from study inclusion until Day 28, or ICU/hospital discharge or death, whichever occurs first
ICU length of stay
Tidsramme: Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first
Data about ICU length of stay will be retrieved from electronic medical records.
Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first
Hospital length of stay
Tidsramme: Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first
Data about hospital length of stay will be retrieved from electronic medical records.
Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first
ICU mortality
Tidsramme: Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first
Data about ICU mortality will be retrieved from electronic medical records.
Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first
Hospital mortality
Tidsramme: Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first
Data about hospital mortality will be retrieved from electronic medical records.
Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first
Day 28 all-cause mortality
Tidsramme: Collected from study inclusion until Day 28 or death, whichever occurs first
Data about day 28 all-cause mortality will be retrieved from electronic medical records.
Collected from study inclusion until Day 28 or death, whichever occurs first
ICU-free days through day 28
Tidsramme: Collected from ICU discharge until Day 28 or death, whichever occurs first
Data about ICU-free days through day 28 will be retrieved from electronic medical records.
Collected from ICU discharge until Day 28 or death, whichever occurs first
Hospital-free days through day 28
Tidsramme: Collected from hospital discharge until Day 28 or death, whichever occurs first
Data about hospital-free days through day 28 will be retrieved from electronic medical records.
Collected from hospital discharge until Day 28 or death, whichever occurs first
Time to ICU discharge alive through day 28
Tidsramme: Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first
Data about time to ICU discharge alive through day 28 will be retrieved from electronic medical records.
Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first
Time to hospital discharge alive through day 28
Tidsramme: Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first
Data about time to hospital discharge alive through day 28 will be retrieved from electronic medical records.
Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Radboud University Medical Center

Efterforskere

  • Ledende efterforsker: Jonne Doorduin, PhD, Radboud University Medical Centre (Radboudumc)
  • Studiestol: Leo Heunks, M.D., PhD, Radboud University Medical Centre (Radboudumc)

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

1. oktober 2026

Primær færdiggørelse (Anslået)

1. september 2028

Studieafslutning (Anslået)

1. december 2028

Datoer for studieregistrering

Først indsendt

9. september 2026

Først indsendt, der opfyldte QC-kriterier

14. september 2026

Først opslået (Faktiske)

15. september 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

15. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

14. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • NL-011458

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