Diaphragm DysfunctionDISSECTNCT07819864
Diaphragm Hibernation and Its Driving Factors in Mechanically Ventilated ICU Patients
An observational study of Diaphragm Dysfunction and Weaning Invasive Mechanical Ventilation, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diaphragm Dysfunction, Weaning Invasive Mechanical Ventilation, Respiratory Failure, ICU
- How many people
- 112 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2026to Dec 2028
- Phase
- Observational
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site
Radboud University Medical Center (Radboudumc)
Nijmegen, Gelderland, 6525 GA
Jonne Doorduin, PhD, 0031650155757, jonne.doorduin@radboudumc.nl
About this study
Official title: 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.
Read more
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.
- Keywords
- Diaphragm, Weaning, Invasive Mechanical Ventilation, Diaphragm Hibernation
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood C reactive protein level
C reactive protein will be assessed by blood sample.
Measured: 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
Procalcitonin will be assessed by blood sample.
Measured: 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
Metabolic biomarkers will be assessed by blood sample using OLINK Target 96 panel.
Measured: 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
TNF-α will be assessed by blood sample.
Measured: 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
IL-10 will be assessed by blood sample.
Measured: 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
IL-8 will be assessed by blood sample.
Measured: 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
IL-6 will be assessed by blood sample.
Measured: 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
Ferritin will be assessed by blood sample.
Measured: 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.
Secondary outcomes (13)
Proportion of participants exhibiting diaphragm hibernation during invasive mechanical ventilation
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.
Measured: 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
Data about number of days from intubation to successful extubation will be retrieved from electronic medical records.
Measured: 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
Data about number of days from first SBT to successful extubation will be retrieved from electronic medical records.
Measured: Collected from study inclusion until Day 28, or ICU/hospital discharge or death, whichever occurs first
Incidence of weaning failure
Weaning failure is defined as SBT failure or reintubation within 48 hours. Data will be retrieved from electronic medical records.
Measured: Collected from study inclusion until Day 28, or ICU/hospital discharge or death, whichever occurs first
ICU length of stay
Data about ICU length of stay will be retrieved from electronic medical records.
Measured: Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first
Hospital length of stay
Data about hospital length of stay will be retrieved from electronic medical records.
Measured: Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first
ICU mortality
Data about ICU mortality will be retrieved from electronic medical records.
Measured: Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first
Hospital mortality
Data about hospital mortality will be retrieved from electronic medical records.
Measured: Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first
Day 28 all-cause mortality
Data about day 28 all-cause mortality will be retrieved from electronic medical records.
Measured: Collected from study inclusion until Day 28 or death, whichever occurs first
ICU-free days through day 28
Data about ICU-free days through day 28 will be retrieved from electronic medical records.
Measured: Collected from ICU discharge until Day 28 or death, whichever occurs first
Hospital-free days through day 28
Data about hospital-free days through day 28 will be retrieved from electronic medical records.
Measured: Collected from hospital discharge until Day 28 or death, whichever occurs first
Time to ICU discharge alive through day 28
Data about time to ICU discharge alive through day 28 will be retrieved from electronic medical records.
Measured: Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first
Time to hospital discharge alive through day 28
Data about time to hospital discharge alive through day 28 will be retrieved from electronic medical records.
Measured: Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2026
- Study startOct 2026 (estimated)
- Primary completionSep 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diaphragm DysfunctionStudies of the same condition, open and under way.
- 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
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jonne Doorduin, PhD, Principal investigator, Radboud University Medical Centre (Radboudumc)Leo Heunks, M.D., PhD, Study chair, Radboud University Medical Centre (Radboudumc)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07819864
- Sponsor's protocol ID
- NL-011458
- Acronym
- DISSECT
- Status last verified
- Sep 2026
- First submitted
- 9 Sep 2026
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No