Diving MedicineTriMix17-18NCT03190252
Inflammatory and Cerebrospinal Biochemical Markers in Blood After Trimix Diving
An observational study of Diving Medicine and Inflammation, run by Sahlgrenska University Hospital at 1 site in Sweden.
Trial summary
Research hypothesis Diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas will affect the central nervous system. Diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas will induce inflammatory changes. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Diving Medicine, Inflammation, Central Nervous System Injury
- What is being tested?
- Exposure to oxygen partial pressure of 130 kPa and Exposure to ambient pressure of maximum 11 ATA
- How many people
- 10 participants
- Where
- 1 siteSweden
- Study dates
- 12 Jun 2017to 30 Jan 2019
- 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 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Military divers and individuals approved by the Swedish navy to dive or perform work in hyperbaric environment.
Who may be able to join
- Military diver or individual approved by the Swedish navy to dive or perform work in hyperbaric environments
Who cannot join
- As this is a highly selected population there is no exclusion criteria
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Biokemiska förändringar Vid förhöjt Partialtryck för Syrgas
Research hypothesis
- Diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas will affect the central nervous system.
- Diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas will induce inflammatory changes.
Read more
Objectives:
- To investigate the presence of cerebrospinal biochemical markers in blood after diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas.
- To investigate the presence of inflammatory markers in blood after diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas.
- To investigate the presence of venous gas emboli (VGE) in blood after diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas.
Read the detailed description
When diving with compressed air as breathing gas, a continuous accumulation of nitrogen will take place in the body. The total uptake of nitrogen by the tissues is dependent on the duration and depth of the performed dive. Decompression at the end of a dive can cause accumulated nitrogen to form intravascular bubbles.
Furthermore, at depths greater than 30 meters seawater (msw) the elevated partial pressure of nitrogen in the breathing gas will exert a direct effect on the nervous system. This is known as nitrogen narcosis and can cause altered cognitive function, confusion, behavioural disturbance and altered level of consciousness. The effect of nitrogen narcosis gets more pronounced with increasing diving depth. To avert nitrogen narcosis it is common to reduce the amount of nitrogen in the breathing gas being used. At the same time the amount of oxygen must also be reduced, as partial pressures of oxygen above 1,6kPa could induce seizures. Usually a breathing gas mixture containing helium, nitrogen and oxygen (TriMix) is used.
It has long been considered that decompression sickness (DCS) is caused by bubble formation when dissolved nitrogen at the end of diving comes out of solution. Doppler ultrasound techniques have shown that intravascular gas bubbles could exist even after uneventful dives. Therefore, additional pathophysiological factors must be sought.
There is evidence of an increased inflammatory activity in blood after diving. Signs of neutrophil activation is a common finding. It is not known if hyperbaric exposure in itself is enough to elicit these biochemical changes or if the presence of intravascular nitrogen bubbles is needed.
Studies have shown that biochemical markers of central nervous system (CNS) injury can be detected in blood samples obtained from patients with DCS, metabolic and neurologic disease, during cardiac surgery and after traumatic brain injuries. Such markers can also be seen in blood after sport activities like boxing and breath hold diving. If biochemical markers of CNS injury will be present in blood after hyperbaric exposure is not known.
The Swedish armed forces (SwAF) Diving and Naval Medicine Center (DNC) is responsible for education and training of divers for SwAF. The centre is also responsible for research and development and conduct tests for diving medicine, and tests of underwater equipment.
SwAF DNC will during 2017 and 2018 be responsible for naval dive training including deep dives (up to 90 msw) using TriMix as breathing gas. The partial pressure of oxygen will be kept at 130kPa. The study "Inflammatory and cerebrospinal biochemical markers in blood after TriMix diving - an observational controlled study" will be followed out during these tests. It entails venous blood sampling and cardiac ultrasound.
This is a prospective, controlled observational study (see addendum 08/03/19 below). The study aims to involve at least 16 study subjects. Half of the subjects (at least 8 persons), named the intervention group, dive to depths up to 90msw with an oxygen partial pressure of 130kPa in the TriMix breathing gas. Half of the subjects (at least 8 persons), named the control group, do not dive. The dives are part of the Swedish navy´s training programme for TriMix diving.
Blood samples are obtained from the intervention group before and after diving (two tubes and about 8mL of blood each time, in total 16mL of blood). If possible, a third blood sample are taken about 24 hours after the first sample. Blood samples are obtained from the control group at the same time points as from the intervention group.
Immmediately after diving, cardiac ultrasound will be used to assess presence and duration of VGE in the intervention group.
Signs of DCS will be actively sought.
Addendum 08/03/19: A control group containing non-diving military divers was initially planned. However, difficulties in subject recruitment meant that an appropriate control group could not be formed. It was performed as an observational study without controls.
- Conditions
- Diving Medicine, Inflammation, Central Nervous System Injury
- Being tested
- Exposure to oxygen partial pressure of 130 kPa, Exposure to ambient pressure of maximum 11 ATA
- Keywords
- Diving medicine, Inflammation, Central nervous system injury, Trimix, Decompression sickness, Venous gas emboli
- Medical subject headings
- Inflammation, Decompression Sickness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exposure to oxygen partial pressure of 130 kPaOther
Open sea diving to a maximum depth of 100 msw while breathing Trimix.
Exposure to ambient pressure of maximum 11 ATAOther
Open sea diving to a maximum depth of 100 msw while breathing Trimix.
| Study group | Role | What they receive |
|---|---|---|
| Trimix | Exposure to ambient pressure of maximum 11 ATA breathing Trimix. Exposure to oxygen partial pressure of 130 kPa breathing Trimix. Receives: Other: Exposure to oxygen partial pressure of 130 kPa; Other: Exposure to ambient pressure of maximum 11 ATA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of cerebrospinal and inflammatory biochemical markers in blood
E.g. GFAP, Tau, NfL, JCHL-1, VCAM-1, ICAM-1
Measured: Three months
Secondary outcomes (2)
Presence of Venous Gas Emboli (VGE)
Kisman-Masurel grading
Measured: Five days
Decompression Sickness (DCS)
Clinical diagnosis
Measured: Five days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2017
- Study start12 Jun 2017
- Primary completion30 Jan 2019
- Study completion30 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diving MedicineStudies of the same condition, open and under way.
- More trials run by Sahlgrenska University HospitalThe 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
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sahlgrenska University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Göteborg University, Swedish Armed Forces Diving and Naval Medicine Centre, KTH Royal Institute of Technology
- Responsible party
- Principal investigator, Anders Rosén, Sahlgrenska University Hospital
- Investigators
- Henrik Zetterberg, PhD, Study director, Göteborg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03190252
- Sponsor's protocol ID
- EPN 292-17
- Acronym
- TriMix17-18
- Status last verified
- Mar 2019
- First submitted
- 14 Jun 2017
- Last updated
- 12 Mar 2019
- 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 12 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biokemiska förändringar Vid förhöjt Partialtryck för Syrgas
- ClinicalTrials.gov ID
- NCT03190252
- Acronym / sponsor ID
- TriMix17-18 / EPN 292-17
- Conditions
- Diving Medicine, Inflammation, Central Nervous System Injury
- Keywords
- Diving medicine, Inflammation, Central nervous system injury, Trimix, Decompression sickness, Venous gas emboli
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Sahlgrenska University HospitalUniversity, hospital or other
- Collaborators
- Göteborg University, Swedish Armed Forces Diving and Naval Medicine Centre, KTH Royal Institute of Technology
- Study start
- 12 Jun 2017 (actual)
- Primary completion
- 30 Jan 2019 (actual)
- Study completion
- 30 Jan 2019 (actual)
- First posted
- 16 Jun 2017 (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.
Research hypothesis
- Diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas will affect the central nervous system.
- Diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas will induce inflammatory changes.
Objectives:
- To investigate the presence of cerebrospinal biochemical markers in blood after diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas.
- To investigate the presence of inflammatory markers in blood after diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas.
- To investigate the presence of venous gas emboli (VGE) in blood after diving to depths up to 90msw with an oxygen partial pressure of 130kPa in the breathing gas.
Detailed description
When diving with compressed air as breathing gas, a continuous accumulation of nitrogen will take place in the body. The total uptake of nitrogen by the tissues is dependent on the duration and depth of the performed dive. Decompression at the end of a dive can cause accumulated nitrogen to form intravascular bubbles.
Furthermore, at depths greater than 30 meters seawater (msw) the elevated partial pressure of nitrogen in the breathing gas will exert a direct effect on the nervous system. This is known as nitrogen narcosis and can cause altered cognitive function, confusion, behavioural disturbance and altered level of consciousness. The effect of nitrogen narcosis gets more pronounced with increasing diving depth. To avert nitrogen narcosis it is common to reduce the amount of nitrogen in the breathing gas being used. At the same time the amount of oxygen must also be reduced, as partial pressures of oxygen above 1,6kPa could induce seizures. Usually a breathing gas mixture containing helium, nitrogen and oxygen (TriMix) is used.
It has long been considered that decompression sickness (DCS) is caused by bubble formation when dissolved nitrogen at the end of diving comes out of solution. Doppler ultrasound techniques have shown that intravascular gas bubbles could exist even after uneventful dives. Therefore, additional pathophysiological factors must be sought.
There is evidence of an increased inflammatory activity in blood after diving. Signs of neutrophil activation is a common finding. It is not known if hyperbaric exposure in itself is enough to elicit these biochemical changes or if the presence of intravascular nitrogen bubbles is needed.
Studies have shown that biochemical markers of central nervous system (CNS) injury can be detected in blood samples obtained from patients with DCS, metabolic and neurologic disease, during cardiac surgery and after traumatic brain injuries. Such markers can also be seen in blood after sport activities like boxing and breath hold diving. If biochemical markers of CNS injury will be present in blood after hyperbaric exposure is not known.
The Swedish armed forces (SwAF) Diving and Naval Medicine Center (DNC) is responsible for education and training of divers for SwAF. The centre is also responsible for research and development and conduct tests for diving medicine, and tests of underwater equipment.
SwAF DNC will during 2017 and 2018 be responsible for naval dive training including deep dives (up to 90 msw) using TriMix as breathing gas. The partial pressure of oxygen will be kept at 130kPa. The study "Inflammatory and cerebrospinal biochemical markers in blood after TriMix diving - an observational controlled study" will be followed out during these tests. It entails venous blood sampling and cardiac ultrasound.
This is a prospective, controlled observational study (see addendum 08/03/19 below). The study aims to involve at least 16 study subjects. Half of the subjects (at least 8 persons), named the intervention group, dive to depths up to 90msw with an oxygen partial pressure of 130kPa in the TriMix breathing gas. Half of the subjects (at least 8 persons), named the control group, do not dive. The dives are part of the Swedish navy´s training programme for TriMix diving.
Blood samples are obtained from the intervention group before and after diving (two tubes and about 8mL of blood each time, in total 16mL of blood). If possible, a third blood sample are taken about 24 hours after the first sample. Blood samples are obtained from the control group at the same time points as from the intervention group.
Immmediately after diving, cardiac ultrasound will be used to assess presence and duration of VGE in the intervention group.
Signs of DCS will be actively sought.
Addendum 08/03/19: A control group containing non-diving military divers was initially planned. However, difficulties in subject recruitment meant that an appropriate control group could not be formed. It was performed as an observational study without controls.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trimix | – | Other: Exposure to oxygen partial pressure of 130 kPa, Other: Exposure to ambient pressure of maximum 11 ATAExposure to ambient pressure of maximum 11 ATA breathing Trimix. Exposure to oxygen partial pressure of 130 kPa breathing Trimix. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Military divers and individuals approved by the Swedish navy to dive or perform work in hyperbaric environment.
Key inclusion criteria (1 listed)
- Military diver or individual approved by the Swedish navy to dive or perform work in hyperbaric environments
Key exclusion criteria (1 listed)
- As this is a highly selected population there is no exclusion criteria
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 |
|---|---|---|
| Exposure to oxygen partial pressure of 130 kPaOpen sea diving to a maximum depth of 100 msw while breathing Trimix. | Other | Trimix |
| Exposure to ambient pressure of maximum 11 ATAOpen sea diving to a maximum depth of 100 msw while breathing Trimix. | Other | Trimix |
Primary outcome
Concentration of cerebrospinal and inflammatory biochemical markers in blood
Time frame: Three months
E.g. GFAP, Tau, NfL, JCHL-1, VCAM-1, ICAM-1
2 secondary outcomes
Presence of Venous Gas Emboli (VGE)
Time frame: Five days
Decompression Sickness (DCS)
Time frame: Five days
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 12 Mar 2019.
- Individual participant dataSharing planned: No
Related trials for Diving Medicine
Not yet recruiting
Effect of Hydrogen Gas on Hyperbaric Oxygen Toxicity
Oxygen Toxicity, Oxidative Stress
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.
Henrik Zetterberg, PhD study director
Göteborg University
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 Diving Medicine and Inflammation, run by Sahlgrenska University Hospital at 1 site in Sweden.
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 1 inclusion and 1 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 12 Mar 2019. 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 Sweden. 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?
Concentration of cerebrospinal and inflammatory biochemical markers in blood (time frame: Three months). 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 12 Mar 2019.