Mitochondrial Oxygenation MeasurementNCT04626661
Mitochondrial Oxygen Measurement Variability in Critically Ill Patients (INOX Variability Study)
An observational study of Mitochondrial Oxygenation Measurement and Measurement Error, run by Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mitochondrial Oxygenation Measurement, Measurement Error, Healthy
- What is being tested?
- COMET measurement system
- Type of treatment
- Medical device
- How many people
- 33 participants
- Where
- 1 siteNetherlands
- Study dates
- 15 Jun 2020to 17 May 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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).
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Leiden University Medical Center
Leiden, South Holland, 2333 ZA
About this study
Official title: Mitochondrial Oxygen Measurement Variability in Critically Ill Patients: Validation of the COMET Measurement System
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.
Read the 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.
- Being tested
- COMET measurement system
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
COMET measurement systemDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Health volunteers | 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 critically ill patients and to better explore the effect of time-since-application of the 5-aminolevulinic acid-patches. Receives: Device: COMET measurement system | |
| Patients admitted to the ICU after neurosurgery | This study population will consist of patients undergoing elective neurosurgery with planned postoperative recovery of at least 24 hours in the intensive care unit or medium care unit. Leiden University Medical Center is a neurosurgical center in which a wide variety of surgeries including tumor resection in the posterior cranial fossa (including vestibular schwannoma) are performed. Clinical experience has shown that this cohort of patients are in general, hemodynamically the most stable patients and receive the least amount of interventions compared to other cohorts of patients in the intensive care unit and medium care unit. For these reasons, the cohort of elective neurosurgical patients would be ideal to investigate the reason of the increased between- and within-subject variability of mitochondrial oxygen tension in the intensive care unit and medium care unit setting. Receives: Device: COMET measurement system |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 hours
Secondary outcomes (2)
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.
Measured: 24 hour
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.
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2020
- Study start15 Jun 2020
- Primary completion1 Mar 2023
- Study completion17 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mitochondrial Oxygenation MeasurementStudies 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
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
- Sponsor type
- University, hospital or other
- Collaborators
- Leiden University Medical Center
- Responsible party
- Principal investigator, J.G. van der Bom, Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
- Investigators
- J. G. van der Bom, PhD, MD, Principal investigator, Leiden University Medical CenterM. S. Arbous, PhD,MD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04626661
- Sponsor's protocol ID
- NL71914.058.19
- Status last verified
- May 2024
- First submitted
- 6 Nov 2020
- Last updated
- 7 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Baysan M, Broere M, Wille ME, Bergsma JE, Mik EG, Juffermans NP, Tsonaka R, van der Bom JG, Arbous SM. Description of mitochondrial oxygen tension and its variability in healthy volunteers. PLoS One. 2024 Jun 3;19(6):e0300602. doi: 10.1371/journal.pone.0300602. eCollection 2024.
PubMed 38829894
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mitochondrial Oxygen Measurement Variability in Critically Ill Patients: Validation of the COMET Measurement System
- ClinicalTrials.gov ID
- NCT04626661
- Acronym / sponsor ID
- NL71914.058.19
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Sanquin-LUMC J.J van Rood Center for Clinical Transfusion ResearchUniversity, hospital or other
- Collaborators
- Leiden University Medical Center
- Study start
- 15 Jun 2020 (actual)
- Primary completion
- 1 Mar 2023 (actual)
- Study completion
- 17 May 2023 (actual)
- First posted
- 12 Nov 2020 (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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Health volunteers | – | Device: COMET measurement systemThe 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 critically ill patients and to better explore the effect of time-since-application of the 5-aminolevulinic acid-patches. |
| Patients admitted to the ICU after neurosurgery | – | Device: COMET measurement systemThis study population will consist of patients undergoing elective neurosurgery with planned postoperative recovery of at least 24 hours in the intensive care unit or medium care unit. Leiden University Medical Center is a neurosurgical center in which a wide variety of surgeries including tumor resection in the posterior cranial fossa (including vestibular schwannoma) are performed. Clinical experience has shown that this cohort of patients are in general, hemodynamically the most stable patients and receive the least amount of interventions compared to other cohorts of patients in the intensive care unit and medium care unit. For these reasons, the cohort of elective neurosurgical patients would be ideal to investigate the reason of the increased between- and within-subject variability of mitochondrial oxygen tension in the intensive care unit and medium care unit setting. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| COMET measurement systemPhotonics 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. | Device | Health volunteers, Patients admitted to the ICU after neurosurgery |
Primary outcome
Within-subject variability of mitochondrial oxygenation measurements over a period of 24 hours after ALA-induction
Time frame: 24 hours
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
2 secondary outcomes
Between- and within-subject variability between 3 hour offset 5-aminolevulinic acid-patches
Time frame: 24 hour
Safety of mitochondrial oxygenation measurements
Time frame: 48 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2024.
- Derived from this study: PubMed 38829894Baysan M, Broere M, Wille ME, Bergsma JE, Mik EG, Juffermans NP, Tsonaka R, van der Bom JG, Arbous SM. Description of mitochondrial oxygen tension and its variability in healthy volunteers. PLoS One. 2024 Jun 3;19(6):e0300602. doi: 10.1371/journal.pone.0300602. eCollection 2024.
- Individual participant dataSharing planned: Undecided
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. This study is not recruiting at the moment.
J. G. van der Bom, PhD, MD principal investigator
Leiden University Medical Center
M. S. Arbous, PhD,MD principal investigator
Leiden University Medical Center
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 Mitochondrial Oxygenation Measurement and Measurement Error, run by Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research 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 3 inclusion and 5 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: finished, as of the sponsor's last update on 7 May 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Within-subject variability of mitochondrial oxygenation measurements over a period of 24 hours after ALA-induction (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04626661, which also lists 1 linked publication.
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 7 May 2024.