HypovolemiaPhase 4Volu-FlowNCT05705115
Acetated Ringer´s Solution in Experimental Hypovolemia
A Phase 4 study testing Ringer acetate and Lower body negative pressure in people with Hypovolemia and Fluid Loss, run by Oslo University Hospital at 1 site in Norway.
Trial summary
Intravenous fluids are often given to increase stroke volume and thereby improve global oxygen delivery. The effect is however often transient, but the effect of a fluid bolus on stroke volume and other hemodynamic variables over time are poorly described. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypovolemia, Fluid Loss, Hemodynamic Instability
- What is being tested?
- Ringer acetate and Lower body negative pressure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteNorway
- Study dates
- 2 Mar 2024to 30 Oct 2025
- Phase
- Phase 4
- 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 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination and focused cardiac ultrasound
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
- Sex and Contraceptive/Barrier Requirements 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.
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: A Randomized Study to Investigate Central and Cerebral Hemodynamic Effects and Volume Kinetics of Ringer´s Acetate Compared With no Intravenous Fluids, During Experimental Hypovolemia Compared With Euvolemia, in Healthy Human Volunteers
Intravenous fluids are often given to increase stroke volume and thereby improve global oxygen delivery. The effect is however often transient, but the effect of a fluid bolus on stroke volume and other hemodynamic variables over time are poorly described. The volume effect of a fluid bolus (effect on blood volume) can be calculated by measuring Haemoglobin. The purpose of this study is to elucidate the hemodynamic effects of a fluid bolus during normovolemia and hypovolemia in healthy volunteers. Study details include:
- Study Duration: 2 visits of approximately 2 h duration each + follow-up visit. Visits 1 and 2 are at least 2 days apart. Number of Participants: A maximum of 15 participants will be enrolled to study intervention such that 12 evaluable participants complete the study
Read the detailed description
Administration of intravenous fluids is one of the most commonly performed procedures in anaesthesia, critical care and emergency medicine. Intravenous fluids can be given to achieve specific goals depending on the type of fluid, but often, fluid is given simply to expand the intravascular volume. The volume-expanding effect of intravenous fluids is however time-dependent, and often of limited duration as fluid is distributed out of the intravascular space and eliminated mainly in the kidneys.
The goal of intravascular volume expansion is to improve haemodynamic variables, such as SV, CO and ABP. The reasoning is that volume expansion increases SV mainly mediated by the Frank-Starling mechanism. The degree to which SV increases with volume expansion is termed fluid responsiveness.1 The increase in SV does however in most cases seem to be transient. The reason for the transient nature of the hemodynamic response is not known, but may be related to reduction in intravascular volume expansion as described above or other factors, such as vasodilation.
Calculation of volume expansion:
The volume-expanding effect of intravenous fluids has been studied by measuring concentration of hemoglobin. Under the assumption that hemoglobin is evenly distributed in, and does not leave the intravascular space, intravascular volume can be calculated and kinetic studies of the volume effect (volume kinetics) can be performed.
Hb = intravascular amount of hemoglobin V0 = Intravascular volume at time 0 Vt = Intravascular volume at time t [Hb]0 = Hemoglobin concentration at time 0 [Hb]t = Hemoglobin concentration at time t Eq1: (Hb)o= Hb/Vo. Vo = Hb/(Hb)o Eq 2: (Hb)t= Hb/Vt. Vo = Hb/(Hb)t.
Assuming that the amount of hemoglobin is constant, from Eq 1 ang Eq 2, it follows that:
Eq 3: Vt/V0=(Hb)o/(Hb)t which therefore gives the relative value of intravascular volume at time=t to compared to time=0; Vt_rel.
Kinetic model of outcomes:
Similar to the volume expansion, the relative value of the hemodynamic variables compared to baseline can be calculated, expressed as value at time=t, Vt.
A pharmacokinetic model can then be fitted to the observations. In a two-compartment model, the relative value (e.g. volume) of the observed value at time=t (Vt) can be described as:
Eq 4: V_(t_rel)=D(〖Ae〗^(-αt)+〖Be〗^(-βt))
A one-compartment model can be described as:
Eq 5: V_(t_rel)=D(〖Ae〗^(-αt)) A two-compartment model will typically describe a rapid equilibration with one compartment and a slower elimination. Initially the reduction in Vt is dominated by distribution, and later by the slower elimination. Each of these effects have their own half-lives, given by α and β. For a one-compartment model, the reduction in Vt is best described by a single half-life.
LBNP-model:
LBNP is a model that has been used for several decades. 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.
The volume kinetics of intravenous fluids has been shown to be affected by volume status, with a longer lasting volume effect during hypovolaemia.The effects of volume status on the hemodynamic response to intravenous fluids has been less explored.
Aim of the study The aim of the present study is to explore the effects over time of an intravenous fluid bolus. The effects on the volume expanding effects and the hemodynamic effects will be measured.
- Conditions
- Hypovolemia, Fluid Loss, Hemodynamic Instability
- Being tested
- Ringer acetate, Lower body negative pressure
- Medical subject headings
- Hypovolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ringer acetateDrug
Ringer acetate 5 ml/kg.
Lower body negative pressureOther
Lower body negative pressure, 40 mmHg. Experimental hypovolemia.
| Study group | Role | What they receive |
|---|---|---|
| LBNP 0 + no intravenous fluid | No intervention | Not described |
| LBNP 0 + Ringer's acetate | Experimental | Not described Receives: Drug: Ringer acetate |
| LBNP 40 + no intravenous fluid | Active comparator | Not described Receives: Other: Lower body negative pressure |
| LBNP 40 + Ringer's acetate | Experimental | Not described Receives: Drug: Ringer acetate; Other: Lower body negative pressure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac stroke volume
Half-life of change in cardiac stroke volume
Measured: 120 minutes
Secondary outcomes (2)
Intravascular volume
Half-life of change in intravascular volume
Measured: 120 minutes
Middle cerebral artery blood flow velocity
Half-life of change in middle cerebral artery blood flow velocity
Measured: 120 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2023
- Study start2 Mar 2024
- Primary completion30 Oct 2025
- Study completion30 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- * Block randomized * Placebo controlled * Single center * Crossover * Factorial 2x2
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Akershus
- Responsible party
- Principal investigator, Lars Øivind Høiseth, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05705115
- Sponsor's protocol ID
- Volu-Flow
- Acronym
- Volu-Flow
- Status last verified
- Oct 2025
- First submitted
- 21 Jan 2023
- Last updated
- 2 Jun 2026
- 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 2 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Study to Investigate Central and Cerebral Hemodynamic Effects and Volume Kinetics of Ringer´s Acetate Compared With no Intravenous Fluids, During Experimental Hypovolemia Compared With Euvolemia, in Healthy Human Volunteers
- ClinicalTrials.gov ID
- NCT05705115
- Acronym / sponsor ID
- Volu-Flow / Volu-Flow
- Conditions
- Hypovolemia, Fluid Loss, Hemodynamic Instability
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- University Hospital, Akershus
- Study start
- 2 Mar 2024 (actual)
- Primary completion
- 30 Oct 2025 (actual)
- Study completion
- 30 Oct 2025 (actual)
- First posted
- 30 Jan 2023 (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.
Intravenous fluids are often given to increase stroke volume and thereby improve global oxygen delivery. The effect is however often transient, but the effect of a fluid bolus on stroke volume and other hemodynamic variables over time are poorly described. The volume effect of a fluid bolus (effect on blood volume) can be calculated by measuring Haemoglobin. The purpose of this study is to elucidate the hemodynamic effects of a fluid bolus during normovolemia and hypovolemia in healthy volunteers. Study details include:
- Study Duration: 2 visits of approximately 2 h duration each + follow-up visit. Visits 1 and 2 are at least 2 days apart. Number of Participants: A maximum of 15 participants will be enrolled to study intervention such that 12 evaluable participants complete the study
Detailed description
Administration of intravenous fluids is one of the most commonly performed procedures in anaesthesia, critical care and emergency medicine. Intravenous fluids can be given to achieve specific goals depending on the type of fluid, but often, fluid is given simply to expand the intravascular volume. The volume-expanding effect of intravenous fluids is however time-dependent, and often of limited duration as fluid is distributed out of the intravascular space and eliminated mainly in the kidneys.
The goal of intravascular volume expansion is to improve haemodynamic variables, such as SV, CO and ABP. The reasoning is that volume expansion increases SV mainly mediated by the Frank-Starling mechanism. The degree to which SV increases with volume expansion is termed fluid responsiveness.1 The increase in SV does however in most cases seem to be transient. The reason for the transient nature of the hemodynamic response is not known, but may be related to reduction in intravascular volume expansion as described above or other factors, such as vasodilation.
Calculation of volume expansion:
The volume-expanding effect of intravenous fluids has been studied by measuring concentration of hemoglobin. Under the assumption that hemoglobin is evenly distributed in, and does not leave the intravascular space, intravascular volume can be calculated and kinetic studies of the volume effect (volume kinetics) can be performed.
Hb = intravascular amount of hemoglobin V0 = Intravascular volume at time 0 Vt = Intravascular volume at time t [Hb]0 = Hemoglobin concentration at time 0 [Hb]t = Hemoglobin concentration at time t Eq1: (Hb)o= Hb/Vo. Vo = Hb/(Hb)o Eq 2: (Hb)t= Hb/Vt. Vo = Hb/(Hb)t.
Assuming that the amount of hemoglobin is constant, from Eq 1 ang Eq 2, it follows that:
Eq 3: Vt/V0=(Hb)o/(Hb)t which therefore gives the relative value of intravascular volume at time=t to compared to time=0; Vt_rel.
Kinetic model of outcomes:
Similar to the volume expansion, the relative value of the hemodynamic variables compared to baseline can be calculated, expressed as value at time=t, Vt.
A pharmacokinetic model can then be fitted to the observations. In a two-compartment model, the relative value (e.g. volume) of the observed value at time=t (Vt) can be described as:
Eq 4: V_(t_rel)=D(〖Ae〗^(-αt)+〖Be〗^(-βt))
A one-compartment model can be described as:
Eq 5: V_(t_rel)=D(〖Ae〗^(-αt)) A two-compartment model will typically describe a rapid equilibration with one compartment and a slower elimination. Initially the reduction in Vt is dominated by distribution, and later by the slower elimination. Each of these effects have their own half-lives, given by α and β. For a one-compartment model, the reduction in Vt is best described by a single half-life.
LBNP-model:
LBNP is a model that has been used for several decades. 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.
The volume kinetics of intravenous fluids has been shown to be affected by volume status, with a longer lasting volume effect during hypovolaemia.The effects of volume status on the hemodynamic response to intravenous fluids has been less explored.
Aim of the study The aim of the present study is to explore the effects over time of an intravenous fluid bolus. The effects on the volume expanding effects and the hemodynamic effects will be measured.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- * Block randomized * Placebo controlled * Single center * Crossover * Factorial 2x2
| Arm | Type | Receives |
|---|---|---|
| LBNP 0 + no intravenous fluid | No intervention | – |
| LBNP 0 + Ringer's acetate | Experimental | Drug: Ringer acetate |
| LBNP 40 + no intravenous fluid | Active comparator | Other: Lower body negative pressure |
| LBNP 40 + Ringer's acetate | Experimental | Drug: Ringer acetate, Other: Lower body negative pressure |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination and focused cardiac ultrasound
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
- Sex and Contraceptive/Barrier Requirements 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
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 |
|---|---|---|
| Ringer acetateRinger acetate 5 ml/kg. | Drug | LBNP 0 + Ringer's acetate, LBNP 40 + Ringer's acetate |
| Lower body negative pressureLower body negative pressure, 40 mmHg. Experimental hypovolemia. | Other | LBNP 40 + Ringer's acetate, LBNP 40 + no intravenous fluid |
Primary outcome
Cardiac stroke volume
Time frame: 120 minutes
Half-life of change in cardiac stroke volume
2 secondary outcomes
Intravascular volume
Time frame: 120 minutes
Middle cerebral artery blood flow velocity
Time frame: 120 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 2 Jun 2026.
- Individual participant dataSharing planned: No
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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 4 study testing Ringer acetate and Lower body negative pressure in people with Hypovolemia and Fluid Loss, 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 6 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 2 Jun 2026. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 stroke volume (time frame: 120 minutes). 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 2 Jun 2026.