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

14 september 2026 bijgewerkt door: 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.

Studie Overzicht

Toestand

Nog niet aan het werven

Conditie

Studietype

Observationeel

Inschrijving (Geschat)

112

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

  • Nederland
    • Gelderland
      • Nijmegen, Gelderland, Nederland, 6525 GA
        • Radboud University Medical Center (Radboudumc)
        • Contact:

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Bemonsteringsmethode

Niet-waarschijnlijkheidssteekproef

Studie Bevolking

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.

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

Cohorten en interventies

Groep / Cohort
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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Blood C reactive protein level
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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.

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Proportion of participants exhibiting diaphragm hibernation during invasive mechanical ventilation
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Radboud University Medical Center

Onderzoekers

  • Hoofdonderzoeker: Jonne Doorduin, PhD, Radboud University Medical Centre (Radboudumc)
  • Studie stoel: Leo Heunks, M.D., PhD, Radboud University Medical Centre (Radboudumc)

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

1 oktober 2026

Primaire voltooiing (Geschat)

1 september 2028

Studie voltooiing (Geschat)

1 december 2028

Studieregistratiedata

Eerst ingediend

9 september 2026

Eerst ingediend dat voldeed aan de QC-criteria

14 september 2026

Eerst geplaatst (Werkelijk)

15 september 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

15 september 2026

Laatste update ingediend die voldeed aan QC-criteria

14 september 2026

Laatst geverifieerd

1 september 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • NL-011458

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

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