NCT07082569

Brief Summary

The goal of this clinical trial is to explore whether different modes of mechanical ventilation affect pupillary constriction velocities in critically ill patients without brain injury. The study aims to determine whether the type of mechanical ventilation (volume control, pressure control, or pressure-regulated volume control) influences the maximum and mean constriction velocity measured by automated pupillometry. The trial also investigates whether changes in pupil dynamics reflect subtle alterations in brainstem-autonomic interaction induced by ventilation mode. The comparison involves volume control, pressure control, and pressure-regulated volume control in a randomized crossover design to assess whether ventilation mode has a measurable effect on pupil response. Eligible participants will be intubated ICU patients receiving assist control ventilation who are not yet ready for spontaneous breathing trials. Serial pupillometry measurements will be conducted while participants are ventilated with each mode for at least 15 minutes. Sedation and lighting conditions will remain consistent throughout the protocol. Participants with acute or chronic neurologic conditions or ventilator dyssynchrony will be excluded.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
36

participants targeted

Target at P25-P50 for not_applicable

Timeline
5mo left

Started Jul 2025

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress71%
Jul 2025Sep 2026

First Submitted

Initial submission to the registry

July 5, 2025

Completed
10 days until next milestone

Study Start

First participant enrolled

July 15, 2025

Completed
9 days until next milestone

First Posted

Study publicly available on registry

July 24, 2025

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 15, 2025

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2026

Expected
Last Updated

July 24, 2025

Status Verified

July 1, 2025

Enrollment Period

2 months

First QC Date

July 5, 2025

Last Update Submit

July 23, 2025

Conditions

Mechanical VentilationCritical Illness

Keywords

Critical illnessMechanical ventilationPupillary light reflexAutomated pupillometryNeurological Pupil Index

Outcome Measures

Primary Outcomes (1)

  • Maximum Pupillary Constriction Velocity

    Change in maximum pupillary constriction velocity (mm/s) in response to standardized light stimulus, as measured by the NPi-200 pupillometer, under three modes of mechanical ventilation: Volume Control (VC), Pressure Control (PC), and Pressure-Regulated Volume Control (PRVC).

    At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).

Secondary Outcomes (6)

  • Neurological Pupil Index (NPi)

    At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).

  • Constriction Latency

    At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).

  • Dilation Velocity

    At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).

  • Maximum Pupil Diameter

    At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).

  • Minimum Pupil Diameter

    At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).

  • +1 more secondary outcomes

Other Outcomes (11)

  • Exploratory Outcome Measure - Heart Rate Variability (HRV)

    Time interval between 15-30 minutes after the initiation of each ventilation mode (VC, PC, PRVC)

  • Systolic Blood Pressure (mmHg)

    At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).

  • Diastolic Blood Pressure (mmHg)

    At 30 minutes after each ventilation mode initiation (VC, PC, PRVC).

  • +8 more other outcomes

Study Arms (6)

Sequence A: VC → PC → PRVC

EXPERIMENTAL

Participants receive mechanical ventilation in the following sequence: Volume Control (VC), followed by Pressure Control (PC), then Pressure-Regulated Volume Control (PRVC). Pupillometry is performed after each mode following a 15-minute stabilization period.

Other: Volume Control VentilationOther: Pressure Control VentilationOther: Pressure-Regulated Volume Control (PRVC)

Sequence B: VC → PRVC → PC

OTHER

Participants receive mechanical ventilation in the following sequence: Volume Control (VC), followed by Pressure-Regulated Volume Control (PRVC), then Pressure Control (PC). Pupillometry is performed after each mode following a 15-minute stabilization period.

Other: Volume Control VentilationOther: Pressure Control VentilationOther: Pressure-Regulated Volume Control (PRVC)

Sequence C: PC → VC → PRVC

OTHER

Participants receive mechanical ventilation in the following sequence: Pressure Control (PC), followed by Volume Control (VC), then Pressure-Regulated Volume Control (PRVC). Pupillometry is performed after each mode following a 15-minute stabilization period.

Other: Volume Control VentilationOther: Pressure Control VentilationOther: Pressure-Regulated Volume Control (PRVC)

Sequence D: PC → PRVC → VC

OTHER

Participants receive mechanical ventilation in the following sequence: Pressure Control (PC), followed by Pressure-Regulated Volume Control (PRVC), then Volume Control (VC). Pupillometry is performed after each mode following a 15-minute stabilization period.

Other: Volume Control VentilationOther: Pressure Control VentilationOther: Pressure-Regulated Volume Control (PRVC)

Sequence E: PRVC → VC → PC

OTHER

Participants receive mechanical ventilation in the following sequence: Pressure-Regulated Volume Control (PRVC), followed by Volume Control (VC), then Pressure Control (PC). Pupillometry is performed after each mode following a 15-minute stabilization period.

Other: Volume Control VentilationOther: Pressure Control VentilationOther: Pressure-Regulated Volume Control (PRVC)

Sequence F: PRVC → PC → VC

OTHER

Participants receive mechanical ventilation in the following sequence: Pressure-Regulated Volume Control (PRVC), followed by Pressure Control (PC), then Volume Control (VC). Pupillometry is performed after each mode following a 15-minute stabilization period.

Other: Volume Control VentilationOther: Pressure Control VentilationOther: Pressure-Regulated Volume Control (PRVC)

Interventions

Volume Control VentilationOTHER

Standard mode of mechanical ventilation delivering a preset tidal volume. Commonly used in ICU patients requiring controlled ventilation.

Sequence A: VC → PC → PRVCSequence B: VC → PRVC → PCSequence C: PC → VC → PRVCSequence D: PC → PRVC → VCSequence E: PRVC → VC → PCSequence F: PRVC → PC → VC
Pressure Control VentilationOTHER

Pressure-targeted ventilation mode that delivers breaths at a fixed pressure. Commonly used in critically ill patients.

Sequence A: VC → PC → PRVCSequence B: VC → PRVC → PCSequence C: PC → VC → PRVCSequence D: PC → PRVC → VCSequence E: PRVC → VC → PCSequence F: PRVC → PC → VC
Pressure-Regulated Volume Control (PRVC)OTHER

Hybrid ventilation mode that automatically adjusts inspiratory pressure to achieve a preset tidal volume.

Sequence A: VC → PC → PRVCSequence B: VC → PRVC → PCSequence C: PC → VC → PRVCSequence D: PC → PRVC → VCSequence E: PRVC → VC → PCSequence F: PRVC → PC → VC

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adult patients (≥18 years old)
  • Receiving positive-pressure mechanical ventilation
  • Under light or no sedation (e.g., RASS score between -2 and 0)
  • Clinically assessed by the treating physician as not yet ready for weaning from mechanical ventilation
  • Hemodynamically stable at the time of measurement
  • Presence of an arterial catheter in place for blood gas analysis

You may not qualify if:

  • Acute or chronic neurological disease affecting brainstem function or pupillary responses
  • Dyssynchrony with the ventilator or need for high ventilatory support adjustments
  • Facial injuries, edema, or conditions precluding accurate pupillometry
  • Use of neuromuscular blocking agents within the prior 6 hours
  • Severe metabolic or acid-base imbalances that may influence autonomic regulation
  • Concurrent participation in another interventional study that could affect neurological or autonomic outcomes

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

!st ICU dpt., Evangelismos Hospital

Athens, 10676, Greece

Location

Related Publications (6)

  • Sibbald B, Roberts C. Understanding controlled trials. Crossover trials. BMJ. 1998 Jun 6;316(7146):1719. doi: 10.1136/bmj.316.7146.1719. No abstract available.

    PMID: 9614025BACKGROUND

  • World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191-4. doi: 10.1001/jama.2013.281053. No abstract available.

    PMID: 24141714BACKGROUND

  • Muppidi S, Adams-Huet B, Tajzoy E, Scribner M, Blazek P, Spaeth EB, Frohman E, Davis S, Vernino S. Dynamic pupillometry as an autonomic testing tool. Clin Auton Res. 2013 Dec;23(6):297-303. doi: 10.1007/s10286-013-0209-7. Epub 2013 Jul 24.

    PMID: 23880969BACKGROUND

  • Bassi TG, Rohrs EC, Fernandez KC, Ornowska M, Nicholas M, Gani M, Evans D, Reynolds SC. Transvenous Diaphragm Neurostimulation Mitigates Ventilation-associated Brain Injury. Am J Respir Crit Care Med. 2021 Dec 15;204(12):1391-1402. doi: 10.1164/rccm.202101-0076OC.

    PMID: 34491883BACKGROUND

  • Cinnella G, Conti G, Lofaso F, Lorino H, Harf A, Lemaire F, Brochard L. Effects of assisted ventilation on the work of breathing: volume-controlled versus pressure-controlled ventilation. Am J Respir Crit Care Med. 1996 Mar;153(3):1025-33. doi: 10.1164/ajrccm.153.3.8630541.

    PMID: 8630541BACKGROUND

  • Walter K. Mechanical Ventilation. JAMA. 2021 Oct 12;326(14):1452. doi: 10.1001/jama.2021.13084. No abstract available.

    PMID: 34636861BACKGROUND

MeSH Terms

Conditions

Critical Illness

Condition Hierarchy (Ancestors)

Disease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Charikleia S Vrettou, MD, PhD

    !st ICU dpt., Evangelismos General Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Charikleia S. Vrettou, MD, PhD

CONTACT

+302132105621vrettou@hotmail.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
The outcome assessor will be masked to the ventilation mode sequence applied during each pupillometry measurement. Pupillometry data will be anonymized and coded prior to statistical analysis to prevent bias in outcome evaluation.
Purpose
OTHER
Intervention Model
CROSSOVER
Model Details: Each participant will receive three different modes of mechanical ventilation (Volume Control, Pressure Control, Pressure-Regulated Volume Control) in a randomized order. Pupillometry measurements will be taken after each mode, with a 15-minute washout period between modes.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

July 5, 2025

First Posted

July 24, 2025

Study Start

July 15, 2025

Primary Completion

September 15, 2025

Study Completion (Estimated)

September 30, 2026

Last Updated

July 24, 2025

Record last verified: 2025-07

Data Sharing

IPD Sharing
Will share

De-identified individual participant data (IPD) related to primary and secondary outcome measures will be made available to other researchers upon reasonable request, after publication of the main study results.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
Beginning 6 months after publication of the primary manuscript and continuing for 3 years.
Access Criteria
Access will be granted to qualified researchers for scientifically sound proposals. Requesters will need to submit a brief proposal outlining the purpose and methods of the secondary analysis.
More information

Locations

GR(1)