Mitochondrial Oxygen Measurement Variability in Critically Ill Patients (INOX Variability Study)

Healthy Clinical Trial

Official title:

Mitochondrial Oxygen Measurement Variability in Critically Ill Patients: Validation of the COMET Measurement System

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04626661
• Other study ID #: NL71914.058.19
• Status: Completed
• Start date: June 15, 2020
• Est. completion date: May 17, 2023

Study information

• Verified date: May 2024
• Source: Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: May 17, 2023
• Est. primary completion date: March 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Healthy
• Measurement Error
• Mitochondrial Oxygenation Measurement

Intervention

Device:
• COMET measurement system
Photonics Healthcare B.V. has developed an innovative non-invasive bedside monitoring system to measure Cellular Oxygen METabolism (the COMET).The COMET's non-invasive cutaneous mitoPO2 measurements rely on the protoporphyrin IX-triple state lifetime technique (PpIX-TSLT). This technique measures oxygen by oxygen-dependent quenching of delayed fluorescence lifetime of 5-aminolevulinic acid-induced mitochondrial PpIX (protoporphyrin IX). PpIX is the final precursor of haem in the haem biosynthesis pathway and is synthetized in the mitochondria. Administration of exogenous 5-aminolevulinic acid enhances PpIX to detectable levels and enhances mitochondrial origin of the delayed fluorescence signal. Measurements are based on the detection of time of extinction of red light emitted by the tissue following excitation with green light. The technique has been tested and calibrated for use in isolated organs and in vivo.

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden	Zuid-Holland

Sponsors (2)

Lead Sponsor	Collaborator
Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research	Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Within-subject variability of mitochondrial oxygenation measurements over a period of 24 hours after ALA-induction	To describe the between- and within-subject variability (assessed by standard deviation) of mitoPO2 measurements over a period of 24 hours after ALA-induction in healthy volunteers and in neurosurgical patients	24 hours
Secondary	Between- and within-subject variability between 3 hour offset 5-aminolevulinic acid-patches	The goal is to describe the difference in the between-subject and within-subject variability between 3 hour offset 5-aminolevulinic acid patches at each time point. The hypothesis is that seen differences can be attributed to the patches itself.	24 hour
Secondary	Safety of mitochondrial oxygenation measurements	Description of the adverse and serious adverse events during and after mitochondrial oxygenation measurements, both in neurosurgical patients admitted to the intensive care unit or medium care unit after their operation, and in healthy volunteers.	48 hours