Clinical trial NCT04626661: Mitochondrial Oxygen Measurement Variability in Critically Ill Patients (INOX Variability Study)
Official title: Mitochondrial Oxygen Measurement Variability in Critically Ill Patients: Validation of the COMET Measurement System
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Mitochondrial Oxygenation Measurement
Measurement Error
Healthy
Lead sponsor: Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
Sponsor class: OTHER
Collaborators: name: Leiden University Medical Center
First posted: 2020-11-12
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will consist, initially, of healthy volunteers. This group was chosen to perform measurements on, to eliminate the effect of critical illness and interventions on the ICU and to better explore the effect of time-since-application of the ALA-patches. Neurosurgical ICU/MC patients will subsequently be included to further explore the effect of critical illness (ICU admission). Since this cohort of patients receives minimal interventions, they are ideal to limit potential affecters on the between- and therefore also the within-subject variability.

Brief summary: To determine the between- and within-subject variability of the mitochondrial oxygenation measurement with the COMET device over time in healthy subjects and in hemodynamically stable subjects admitted to the intensive care unit.

Detailed description: Rationale:

Recent studies have shown the potential of a protoporphyrin IX-triple state lifetime technique to measure mitochondrial oxygen tension (mitoPO2) in vivo, which possibly is an early indicator of oxygen disbalance in the cell. With the advent of the COMET measurement system, steps have been made to determine the feasibility of this measurement method. The INOX ICU-2 study (parent study) aims to tailor transfusion therapies to individual intensive care unit (ICU) patients based on mitochondrial oxygen tension. In the pilot study of the INOX ICU-2 study, in which the COMET measurement system was used on critically ill patients receiving red blood cell transfusion, an increase in the between- and within-subject variability was observed over time. This deviation was not explored during the development of the COMET measurement system. Therefore, we aim to determine the between- and within-subject variability of this measurement in healthy subjects and in hemodynamically stable subjects at the intensive care unit.

Main objectives:

To describe the between- and within-subject variability of mitoPO2 measurements during a 24 hour period after 5- aminolevulinic acid (ALA)-induction among healthy volunteers and among neurosurgical patients admitted postoperatively to the ICU or MC. Healthy subjects allow for the exploration of the effect of time-since-application of ALA-patch and neurosurgical patients allow for the exploration of a possible effect of ICU-admittance.

Study design:

Prospective cohort study.

Study population:

Healthy volunteers and neurosurgical patients admitted at the ICU or Medium Care(MC) of LUMC after surgery.

Study procedure:

MitoPO2 measurements will be taken in healthy volunteers using two ALA-patches offset to each other by 3 hours, this has been done to observe possible differences in measurements at different time-points after ALA-induction while maintaining other variables stable. Following the healthy volunteers, neurosurgical patients will be included. Patients will undergo neurosurgery as planned and common practice is that no major interventions are needed in the postoperative phase on the ICU/MC. At multiple predefined moments after surgery, mitoPO2 measurements will take place, again using two ALA-patches with a 3 hour offset.

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

The risks are small in this study with no serious adverse events (SAE) known. The burden for participants is small since it involves a non-invasive measurement. We will perform this study first in health volunteers. Following the healthy volunteers, neurosurgical patients will be included. Patients will undergo neurosurgery as planned and common practice is that no major interventions are needed in the postoperative phase on the ICU. Normal clinical practice will continue and will not be altered. These patients will allow for the exploration of a possible effect of ICU admittance.

Eligibility criteria: Inclusion Criteria:

* Age of patient is at least 18 years
* Healthy participants, defined as the absence of active or chronic disease (applicable only to healthy volunteer group).
* Patients are admitted to the ICU or MC after neurosurgery (applicable only to neurosurgery group).

Exclusion Criteria:

* patients without a legal representative in case the patient is not able to give informed consent
* pregnant or breast feeding women since there is no adequate data from the use of ALA in pregnant or breast feeding women
* patients with porphyria and/or known photodermatosis
* patients with hypersensitivity to the active substance or to the plaster material of ALA
* insufficient comprehensibility of the Dutch language

Primary outcomes:
measure: Within-subject variability of mitochondrial oxygenation measurements over a period of 24 hours after ALA-induction
timeFrame: 24 hours
Secondary outcomes:
measure: Between- and within-subject variability between 3 hour offset 5-aminolevulinic acid-patches
timeFrame: 24 hour
measure: Safety of mitochondrial oxygenation measurements
timeFrame: 48 hours
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: Zuid-Holland
Study officials:
affiliation: Leiden University Medical Center
name: J. G. van der Bom, PhD, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiden University Medical Center
name: M. S. Arbous, PhD,MD
role: PRINCIPAL_INVESTIGATOR
References: