HypovolemiaPhase 1NCT05150418
Supplemental Oxygen in Hypovolemia
A Phase 1 study testing Oxygen gas and Air in people with Hypovolemia and Hyperoxia, run by Oslo University Hospital at 1 site in Norway.
Trial summary
Supplemental oxygen is frequently administered in acutely and critically ill patients, specifically, it is often administered in trauma patients to avoid arterial hypoxemia and tissue hypoxia. There is also an increasing focus on potentially deleterious effects of hyperoxia. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypovolemia, Hyperoxia
- What is being tested?
- Oxygen gas and Air
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteNorway
- Study dates
- 26 Nov 2021to 14 Jun 2022
- Phase
- Phase 1
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants are eligible to be included in the study only if all of the following criteria apply:
- Age
- Participant must be 18 years of age inclusive, at the time of signing the informed consent.
- Participant must be under 50 years of age inclusive, at the time of signing the informed consent.
- Type of Participant and Disease Characteristics
- Participants who are overtly healthy as determined by medical evaluation including medical history, heart and lung auscultation, focused cardiac ultrasound and measurement of cardiac conduction times.
Show all 17Show fewer
- Sex and Contraceptive/Barrier Requirements
- Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Male participants: Not applicable.
- Female participants:
- Use of adequate birth control for women of childbearing potential.
- A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile when sexually active. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
- Using at least an acceptable effective contraceptive measure (combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner or sexual abstinence). As a minimum contraception should be maintained until treatment discontinuation.
- or
- Confirmed negative highly sensitive urine or serum pregnancy test at screening. A pregnancy test is performed at any visit before administering IMP if more than 14 days have passed since last pregnancy test. There will be no demand for post-intervention contraception.
- Informed Consent
- Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Who cannot join
- Participants are excluded from the study if any of the following criteria apply:
- Medical Conditions
- Any medical condition limiting physical exertional capacity or requiring regular medication (allergy and contraceptives excepted).
- Pregnancy.
- Breastfeeding.
- History of syncope (syncope of presumed vasovagal nature with known precipitating factor excepted).
- Any known cardiac arrhythmia. Prior/Concomitant Therapy
- Any drug (contraceptives excepted) used on a regular basis for a chronic condition (allergy excepted).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Supplemental Oxygen on Systemic and Cerebral Hemodynamics in Experimental Hypovolemia
Supplemental oxygen is frequently administered in acutely and critically ill patients, specifically, it is often administered in trauma patients to avoid arterial hypoxemia and tissue hypoxia. There is also an increasing focus on potentially deleterious effects of hyperoxia. Further, the hemodynamic response to hyperoxia in hypovolemia is poorly understood.
The present study aims to investigate the effects of supplemental oxygen on systemic and cerebral hemodynamics in simulated hypovolemia in healthy volunteers.
Read the detailed description
The overriding goal for the resuscitation of any critically ill patient is to ensure adequate oxygen delivery. In critically ill patients, SaO2 and PaO2 may be reduced due to lung dysfunction (e.g. atelectasis and shunt flow). Under normal circumstances, SaO2 is near to 100%, and supplemental oxygen can not increase this further. Thus, in this circumstance, providing supplemental oxygen will only increase a small, dissolved proportion. Although this proportion may be a significant fraction in some circumstances, the intention of giving supplemental oxygen is in most circumstances to ensure a high SaO2. Supplemental oxygen has been extensively used in acutely critically ill patients to avoid hypoxemia, and is recommended in severely injured trauma patients, as given by the statement: "Supplemental oxygen must be administered to all severely injured trauma patients." in the ATLS (Advanced Trauma Life Support) guidelines.
Accordingly, supplemental oxygen is often given to trauma patients, often resulting in hyperoxia. The clinical evidence for providing supplemental oxygen in all trauma patients is however scarce. The liberal use of supplemental oxygen has also largely been founded on a perception that supplemental oxygen is harmless, and that it is safer to err on the side of hyperoxia. There is however an increasing focus on possible deleterious effects of hyperoxia, especially in specific clinical circumstances. This has led to recommendations of more restrictive use of supplemental oxygen, often titrated to no more than what is necessary to achieve an adequate arterial oxygen saturation (e.g. in the range 94-98%).
In the initial treatment of trauma patients, detection and treatment of hypovolemia is of paramount importance. Hypovolemia leads to reduced cardiac filling and stroke volume. Under normal circumstances in unanesthetized humans, this is compensated by an increase in systemic vascular resistance and heart rate to maintain a normal or near-normal mean arterial pressure (MAP). At some point, these compensatory mechanisms are exhausted, and MAP typically falls abruptly.
Lower body negative pressure (LBNP) is a model of central hypovolemia where negative pressure is applied to the body from the waist-down. Thereby, blood is displaced from the central compartment of the upper body to the lower extremities and pelvis. The model has been used for more than half a century and is considered useful model for studying hypovolemia in conscious volunteers.
Normobaric hyperoxia induces vasoconstriction and reduced blood flow to several organs, including the brain, heart and skeletal muscle. One could therefore hypothesize hyperoxia leading to both an increased tolerance to hypovolemia mediated by vasoconstriction as well as a reduced tolerance mediated by reduced cerebral blood flow. One study using the LBNP-model did not find that supplemental oxygen significantly affected the hemodynamic response to simulated hypovolemia. This study did however only apply one level of LBNP and did not specifically study cerebral circulation.
Based on the above, there is a need for studies on the effects of normobaric hyperoxia on the hemodynamic response to hypovolemia. In the present study, we will study the effect of supplemental oxygen in the LBNP-model of hypovolemia in a crossover study on healthy volunteers.
In the present study, 15 healthy volunteers will be exposed to LBNP with oxygen or room air in randomized order in a crossover fashion. We will measure cardiac outout, stroke volume and middle cerebral artery blood velocity to explore effects of oxygen on these variables during hypovolemia.
- Conditions
- Hypovolemia, Hyperoxia
- Being tested
- Oxygen gas, Air
- Medical subject headings
- Hypovolemia, Hyperoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oxygen gasDrug
Oxygen 15 l/min
AirDrug
Room air 15 l/min
| Study group | Role | What they receive |
|---|---|---|
| Oxygen | Experimental | Oxygen 15 l/min administered with face mask with reservoir. Receives: Drug: Oxygen gas |
| Room air | Placebo comparator | Room air 15 l/min administered with face mask with reservoir. Receives: Drug: Air |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac output
Cardiac output (stroke volume * heart rate)
Measured: Through LBNP exposure completion, up to 35 minutes
Secondary outcomes (3)
Cardiac stroke volume
Cardiac stroke volume as measured by suprasternal Doppler and volume-clamp method
Measured: Through LBNP exposure completion, up to 35 minutes
Middle cerebral artery blood flow velocity (MCAV)
Middle cerebral artery blood flow velocity (MCAV) as measured by ultrasound Doppler
Measured: Through LBNP exposure completion, up to 35 minutes
Time to decompensation
Time from start LBNP to hemodynamic decompensation
Measured: Through LBNP exposure completion, up to 35 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2021
- Study start26 Nov 2021
- Primary completion14 Jun 2022
- Study completion14 Jun 2022
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 HypovolemiaStudies of the same condition, open and under way.
- More trials run by Oslo 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-blind, randomized, crossover design.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Norwegian Air Ambulance Foundation
- Responsible party
- Principal investigator, Lars Øivind Høiseth, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05150418
- Sponsor's protocol ID
- 1_08-06-2021
- Status last verified
- Jul 2022
- First submitted
- 26 Nov 2021
- Last updated
- 5 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lie SL, Hisdal J, Rehn M, Hoiseth LO. Hemodynamic effects of supplemental oxygen versus air in simulated blood loss in healthy volunteers: a randomized, controlled, double-blind, crossover trial. Intensive Care Med Exp. 2023 Nov 10;11(1):76. doi: 10.1186/s40635-023-00561-z.
PubMed 37947905
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Supplemental Oxygen on Systemic and Cerebral Hemodynamics in Experimental Hypovolemia
- ClinicalTrials.gov ID
- NCT05150418
- Acronym / sponsor ID
- 1_08-06-2021
- Conditions
- Hypovolemia, Hyperoxia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- Norwegian Air Ambulance Foundation
- Study start
- 26 Nov 2021 (actual)
- Primary completion
- 14 Jun 2022 (actual)
- Study completion
- 14 Jun 2022 (actual)
- First posted
- 9 Dec 2021 (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.
Supplemental oxygen is frequently administered in acutely and critically ill patients, specifically, it is often administered in trauma patients to avoid arterial hypoxemia and tissue hypoxia. There is also an increasing focus on potentially deleterious effects of hyperoxia. Further, the hemodynamic response to hyperoxia in hypovolemia is poorly understood.
The present study aims to investigate the effects of supplemental oxygen on systemic and cerebral hemodynamics in simulated hypovolemia in healthy volunteers.
Detailed description
The overriding goal for the resuscitation of any critically ill patient is to ensure adequate oxygen delivery. In critically ill patients, SaO2 and PaO2 may be reduced due to lung dysfunction (e.g. atelectasis and shunt flow). Under normal circumstances, SaO2 is near to 100%, and supplemental oxygen can not increase this further. Thus, in this circumstance, providing supplemental oxygen will only increase a small, dissolved proportion. Although this proportion may be a significant fraction in some circumstances, the intention of giving supplemental oxygen is in most circumstances to ensure a high SaO2. Supplemental oxygen has been extensively used in acutely critically ill patients to avoid hypoxemia, and is recommended in severely injured trauma patients, as given by the statement: "Supplemental oxygen must be administered to all severely injured trauma patients." in the ATLS (Advanced Trauma Life Support) guidelines.
Accordingly, supplemental oxygen is often given to trauma patients, often resulting in hyperoxia. The clinical evidence for providing supplemental oxygen in all trauma patients is however scarce. The liberal use of supplemental oxygen has also largely been founded on a perception that supplemental oxygen is harmless, and that it is safer to err on the side of hyperoxia. There is however an increasing focus on possible deleterious effects of hyperoxia, especially in specific clinical circumstances. This has led to recommendations of more restrictive use of supplemental oxygen, often titrated to no more than what is necessary to achieve an adequate arterial oxygen saturation (e.g. in the range 94-98%).
In the initial treatment of trauma patients, detection and treatment of hypovolemia is of paramount importance. Hypovolemia leads to reduced cardiac filling and stroke volume. Under normal circumstances in unanesthetized humans, this is compensated by an increase in systemic vascular resistance and heart rate to maintain a normal or near-normal mean arterial pressure (MAP). At some point, these compensatory mechanisms are exhausted, and MAP typically falls abruptly.
Lower body negative pressure (LBNP) is a model of central hypovolemia where negative pressure is applied to the body from the waist-down. Thereby, blood is displaced from the central compartment of the upper body to the lower extremities and pelvis. The model has been used for more than half a century and is considered useful model for studying hypovolemia in conscious volunteers.
Normobaric hyperoxia induces vasoconstriction and reduced blood flow to several organs, including the brain, heart and skeletal muscle. One could therefore hypothesize hyperoxia leading to both an increased tolerance to hypovolemia mediated by vasoconstriction as well as a reduced tolerance mediated by reduced cerebral blood flow. One study using the LBNP-model did not find that supplemental oxygen significantly affected the hemodynamic response to simulated hypovolemia. This study did however only apply one level of LBNP and did not specifically study cerebral circulation.
Based on the above, there is a need for studies on the effects of normobaric hyperoxia on the hemodynamic response to hypovolemia. In the present study, we will study the effect of supplemental oxygen in the LBNP-model of hypovolemia in a crossover study on healthy volunteers.
In the present study, 15 healthy volunteers will be exposed to LBNP with oxygen or room air in randomized order in a crossover fashion. We will measure cardiac outout, stroke volume and middle cerebral artery blood velocity to explore effects of oxygen on these variables during hypovolemia.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind, randomized, crossover design.
| Arm | Type | Receives |
|---|---|---|
| Oxygen | Experimental | Drug: Oxygen gasOxygen 15 l/min administered with face mask with reservoir. |
| Room air | Placebo comparator | Drug: AirRoom air 15 l/min administered with face mask with reservoir. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- Participants are eligible to be included in the study only if all of the following criteria apply:
- Age
- Participant must be 18 years of age inclusive, at the time of signing the informed consent.
- Participant must be under 50 years of age inclusive, at the time of signing the informed consent.
- Type of Participant and Disease Characteristics
Key exclusion criteria (8 listed)
- Medical Conditions
- Any medical condition limiting physical exertional capacity or requiring regular medication (allergy and contraceptives excepted).
- Pregnancy.
- Breastfeeding.
- History of syncope (syncope of presumed vasovagal nature with known precipitating factor excepted).
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 |
|---|---|---|
| Oxygen gasOxygen 15 l/min | Drug | Oxygen |
| AirRoom air 15 l/min | Drug | Room air |
Primary outcome
Cardiac output
Time frame: Through LBNP exposure completion, up to 35 minutes
Cardiac output (stroke volume * heart rate)
3 secondary outcomes
Cardiac stroke volume
Time frame: Through LBNP exposure completion, up to 35 minutes
Middle cerebral artery blood flow velocity (MCAV)
Time frame: Through LBNP exposure completion, up to 35 minutes
Time to decompensation
Time frame: Through LBNP exposure completion, up to 35 minutes
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 5 Jul 2022.
- Derived from this study: PubMed 37947905Lie SL, Hisdal J, Rehn M, Hoiseth LO. Hemodynamic effects of supplemental oxygen versus air in simulated blood loss in healthy volunteers: a randomized, controlled, double-blind, crossover trial. Intensive Care Med Exp. 2023 Nov 10;11(1):76. doi: 10.1186/s40635-023-00561-z.
- Individual participant dataSharing planned: No
Related trials for Hypovolemia
RecruitingPhase 4
A Study to Assess the Safety and Efficacy of Centhaquine in Hypovolemic Shock Patients
Hypovolemic Shock
Not yet recruitingObservational study
Inferior Vena Cava Versus Subclavian Vein Collapsibility for Predicting Fluid Responsiveness in Trauma Hemorrhagic Shock
Hemorrhagic Shock, Trauma
Not yet recruitingObservational study
Validation of a Wearable Bioimpedance Sensor for Hydration Monitoring
Dehydration, Hypovolemia
RecruitingPhase 4
Effect of Misoprostol on Fluid Deficit Volume in Hysteroscopic Myomectomy
Fibroids, Uterine, Fluid Deficit
RecruitingObservational study
Fontan Outcomes in Oligemia vs Plethora in Univentricular CHD
Congenital Heart Disease (CHD), Univentricular Heart
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Oxygen gas and Air in people with Hypovolemia and Hyperoxia, run by Oslo University Hospital at 1 site in Norway.
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 17 inclusion and 8 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 5 Jul 2022. 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 Norway. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Cardiac output (time frame: Through LBNP exposure completion, up to 35 minutes). 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 NCT05150418, 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 5 Jul 2022; AzTrials last refreshed its copy on 27 Oct 2026.