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
- Are there results?
- Not yet: the study is under way
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.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diaphragm hIbernation and itS Driving factorS in mEChanically venTilated ICU Patients: the DISSECT Study
- ClinicalTrials.gov ID
- NCT07819864
- Acronym / sponsor ID
- DISSECT / NL-011458
- Keywords
- Diaphragm, Weaning, Invasive Mechanical Ventilation, Diaphragm Hibernation
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Oct 2026 (estimated)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 15 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (7 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Blood C reactive protein level
Time frame: 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.
Blood procalcitonin level
Time frame: 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.
Blood metabolic biomarkers level
Time frame: 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.
Blood TNF-α level
Time frame: 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.
Blood IL-10 level
Time frame: 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.
Blood IL-8 level
Time frame: 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.
Blood IL-6 level
Time frame: 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.
Blood ferritin level
Time frame: 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.
13 secondary outcomes
Proportion of participants exhibiting diaphragm hibernation during invasive mechanical ventilation
Time frame: 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
Time frame: 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
Time frame: Collected from study inclusion until Day 28, or ICU/hospital discharge or death, whichever occurs first
Incidence of weaning failure
Time frame: Collected from study inclusion until Day 28, or ICU/hospital discharge or death, whichever occurs first
ICU length of stay
Time frame: Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first
Hospital length of stay
Time frame: Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first
ICU mortality
Time frame: Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first
Hospital mortality
Time frame: Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first
Day 28 all-cause mortality
Time frame: Collected from study inclusion until Day 28 or death, whichever occurs first
ICU-free days through day 28
Time frame: Collected from ICU discharge until Day 28 or death, whichever occurs first
Hospital-free days through day 28
Time frame: Collected from hospital discharge until Day 28 or death, whichever occurs first
Time to ICU discharge alive through day 28
Time frame: Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first
Time to hospital discharge alive through day 28
Time frame: Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jonne Doorduin, PhD principal investigator
Radboud University Medical Centre (Radboudumc)
Leo Heunks, M.D., PhD study chair
Radboud University Medical Centre (Radboudumc)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diaphragm Dysfunction and Weaning Invasive Mechanical Ventilation, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jinyu Zhou, M.sc. (0031626194204, jinyu.zhou@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood C reactive protein level (time frame: 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.). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.