Healthy VolunteersNCT02167178
The Relationship Between Cardiac Output and Microvascular Visceral Blood Flow
An observational study of Healthy Volunteers, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
Although major surgery is often required to treat abdominal problems, there is a significant risk of death or complication following these operations. By using ultrasound the amount and timing of fluid patients receive during operations can be optimised and the risk of surgery reduced. Read more about this study
- Who is it for?
- Ages 18 to 80 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Administration of 0.9% NaCl solution, Measurement of stroke volume and Measurement of microvascular blood flow
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2013to Aug 2014
- 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 80 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy male volunteers, aged 18-80.
Who may be able to join
- male
- age 18-80 years
- body mass index 20-30kg/m2
Who cannot join
- BMI < 20 or > 30 kg/m2.
- Active cardiovascular disease: uncontrolled hypertension (BP > 160/100), angina, heart failure (class III/IV), arhythmias , right to left cardiac shunt or recent cardiac event.
- Individuals taking beta-adrenergic blocking agents.
- Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial)..
- Metabolic disease: hyper and hypo parathyroidism, untreated hyper and hypothyroidism, Cushing's disease, types 1 or 2 diabetes.
- Active inflammatory bowel disease, or renal disease,
Show all 14Show fewer
- Malignancy
- Clotting dysfunction
- Previous oesophageal surgery
- Individuals with a known history of oesophageal varices
- Individuals with a known history of epistaxis
- Family history of early (<55y) death from cardiovascular disease.
- Known sensitivity to SonoVue
- Known sensitivity to gelofusine
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Nottingham, School of Medicine, Division of Medical Sciences and Graduate Entry Medicine
Derby, Derbyshire, DE22 3DT
About this study
Official title: Investigation of the Relationship Between Oesophageal Doppler Assessed Increases in Cardiac Output and Microvascular Visceral Blood Flow in Healthy Volunteers
Although major surgery is often required to treat abdominal problems, there is a significant risk of death or complication following these operations. By using ultrasound the amount and timing of fluid patients receive during operations can be optimised and the risk of surgery reduced. However, little is known about the exact changes in blood flow in the small vessels of the body in response to fluid. A greater understanding of this may allow for more appropriate care of patients undergoing this type of surgery in the future.
In this study of healthy volunteers we will attempt to better understand how fluid administration guided by ultrasound effects blood flow in large and small vessels, by using two different techniques of ultrasound imaging. A narrow bore (approximately 4-5mm diameter) ultrasound probe will be passed through the nostril and mouth to rest within the oesophagus allowing measurement of blood flow in the main artery, while a second probe will be rested on the volunteer's abdomen and used to record changes in blood flow in small liver blood vessels. Comparison of these two techniques during the administration of fluid will allow us to better understand the relationship between large and small vessel blood flow.
Because different types of fluid may behave in different ways, we will test the effect of two types of fluid commonly used in clinical practice; 'normal' saline solution and gelofusine.
Read the detailed description
Optimizing intravascular volume and cardiac output are essential to ensure adequate organ perfusion in patients who are undergoing major surgery. To enable this cardiac output is frequently monitored during operation using a variety of techniques; one such technique is trans-oesophageal Doppler ultrasound also known as oesophageal Doppler monitoring (ODM). ODM measurement of cardiac output is a less invasive technique than many currently used methods, and has recently been recommended by NICE for adoption in clinical practice.
The matching of microvascular blood flow, cardiac output and fluid administration is advantageous for visceral organs, in marrying demands for oxygen and nutrients to their delivery. However, although there is evidence to suggest that intraoperative ODM directed fluid administration can improve outcomes in the perioperative period, reducing hospital stay and complications, there is little direct evidence that optimization of cardiac output via ODM improves the microvascular blood flow to the visceral organs which are frequently compromised by major surgical interventions. A greater appreciation of the effect of ODM guided fluid replacement on the delivery of blood and hence oxygen and nutrients to these vital organs could help with the development of more refined algorithms for fluid administration in a clinical setting in the future. In our clinical physiology laboratories we regularly employ contrast-enhanced ultrasound (CEUS) using a Phillips iU22, to visualize microvascular blood flow in healthy young and elderly men following a variety of physiological challenges. This minimally invasive ultrasound based imaging technique is ideal for gaining an insight into the effect various physiological interventions have on tissue blood flow and could be readily used to chart changes in visceral microvascular flow following ODM guided fluid optimization. Transference of this investigative approach to a clinical setting has the potential to greatly improve the care of the surgical patient requiring fluid resuscitation.
Different types of intravenous fluids are used in clinical practice. These are primarily crystalloid solutions, such as 0.9% sodium chloride ('normal' saline), or colloidal suspensions, such as gelofusine. There is good experimental evidence that the colloid gelofusine produces a greater effect on cardiac output than an equivalent volume of of saline, but it is unclear if this effect is replicated in the microvasculature.
We will test the hypotheses: (1) cardiac output and stroke volume as measured by ODM are determinants of visceral microvascular blood flow (2) visceral microvascular blood flow in elderly individuals is more closely determined by stroke volume (3) gelofusine produces a greater increase in microvascular blood flow than the same volume of normal saline.
- Conditions
- Healthy Volunteers
- Being tested
- Administration of 0.9% NaCl solution, Measurement of stroke volume, Measurement of microvascular blood flow, Administration of gelofusine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Administration of 0.9% NaCl solutionOther
Also called Normal saline, Saline
Volunteers administered 0.9% NaCl solution in 250ml boluses
Measurement of stroke volumeOther
The measurement of stroke volume will be performed using an Oesophageal Doppler Monitor.
Measurement of microvascular blood flowOther
Also called CEUS, Contrast enhanced ultrasound scan, SonoVue.
Microvascular blood flow will be measured using a contrast enhanced ultrasound scan.
Administration of gelofusineOther
Volunteers administered gelofusine in 250ml boluses
| Study group | Role | What they receive |
|---|---|---|
| Volunteers receiving 0.9% NaCl | Volunteers receiving 0.9% NaCl to optimise stroke volume Receives: Other: Administration of 0.9% NaCl solution; Other: Measurement of stroke volume; Other: Measurement of microvascular blood flow | |
| Volunteers receiving gelofusine | Volunteers receiving gelofusine to optimise stroke volume Receives: Other: Measurement of stroke volume; Other: Measurement of microvascular blood flow; Other: Administration of gelofusine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in microvascular visceral blood flow
Microvascular visceral blood flow is assessed using contrast enhanced ultrasound scanning, following stroke volume optimisation.
Measured: 30 minutes
Secondary outcomes (2)
Change in stroke volume
The change in stroke volume will be assessed using an Oesophageal Doppler Monitor, and will be assessed pre- and post-intravenous fluid administration.
Measured: 30 minutes
Change in haematocrit
The change in the haematocrit will be measured pre- and post-intravenous fluid administration.
Measured: 60 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2014 (estimated)
- Study startJan 2013
- Primary completionMar 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe 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
- Time perspective
- Prospective
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John P Williams, PhD, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02167178
- Sponsor's protocol ID
- A12012012
- Status last verified
- Jan 2015
- First submitted
- 16 Jun 2014
- Last updated
- 27 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Relationship Between Oesophageal Doppler Assessed Increases in Cardiac Output and Microvascular Visceral Blood Flow in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02167178
- Acronym / sponsor ID
- A12012012
- Conditions
- Healthy Volunteers
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Mar 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 18 Jun 2014 (estimated)
- 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.
Although major surgery is often required to treat abdominal problems, there is a significant risk of death or complication following these operations. By using ultrasound the amount and timing of fluid patients receive during operations can be optimised and the risk of surgery reduced. However, little is known about the exact changes in blood flow in the small vessels of the body in response to fluid. A greater understanding of this may allow for more appropriate care of patients undergoing this type of surgery in the future.
In this study of healthy volunteers we will attempt to better understand how fluid administration guided by ultrasound effects blood flow in large and small vessels, by using two different techniques of ultrasound imaging. A narrow bore (approximately 4-5mm diameter) ultrasound probe will be passed through the nostril and mouth to rest within the oesophagus allowing measurement of blood flow in the main artery, while a second probe will be rested on the volunteer's abdomen and used to record changes in blood flow in small liver blood vessels. Comparison of these two techniques during the administration of fluid will allow us to better understand the relationship between large and small vessel blood flow.
Because different types of fluid may behave in different ways, we will test the effect of two types of fluid commonly used in clinical practice; 'normal' saline solution and gelofusine.
Detailed description
Optimizing intravascular volume and cardiac output are essential to ensure adequate organ perfusion in patients who are undergoing major surgery. To enable this cardiac output is frequently monitored during operation using a variety of techniques; one such technique is trans-oesophageal Doppler ultrasound also known as oesophageal Doppler monitoring (ODM). ODM measurement of cardiac output is a less invasive technique than many currently used methods, and has recently been recommended by NICE for adoption in clinical practice.
The matching of microvascular blood flow, cardiac output and fluid administration is advantageous for visceral organs, in marrying demands for oxygen and nutrients to their delivery. However, although there is evidence to suggest that intraoperative ODM directed fluid administration can improve outcomes in the perioperative period, reducing hospital stay and complications, there is little direct evidence that optimization of cardiac output via ODM improves the microvascular blood flow to the visceral organs which are frequently compromised by major surgical interventions. A greater appreciation of the effect of ODM guided fluid replacement on the delivery of blood and hence oxygen and nutrients to these vital organs could help with the development of more refined algorithms for fluid administration in a clinical setting in the future. In our clinical physiology laboratories we regularly employ contrast-enhanced ultrasound (CEUS) using a Phillips iU22, to visualize microvascular blood flow in healthy young and elderly men following a variety of physiological challenges. This minimally invasive ultrasound based imaging technique is ideal for gaining an insight into the effect various physiological interventions have on tissue blood flow and could be readily used to chart changes in visceral microvascular flow following ODM guided fluid optimization. Transference of this investigative approach to a clinical setting has the potential to greatly improve the care of the surgical patient requiring fluid resuscitation.
Different types of intravenous fluids are used in clinical practice. These are primarily crystalloid solutions, such as 0.9% sodium chloride ('normal' saline), or colloidal suspensions, such as gelofusine. There is good experimental evidence that the colloid gelofusine produces a greater effect on cardiac output than an equivalent volume of of saline, but it is unclear if this effect is replicated in the microvasculature.
We will test the hypotheses: (1) cardiac output and stroke volume as measured by ODM are determinants of visceral microvascular blood flow (2) visceral microvascular blood flow in elderly individuals is more closely determined by stroke volume (3) gelofusine produces a greater increase in microvascular blood flow than the same volume of normal saline.
Study design
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Volunteers receiving 0.9% NaCl | – | Other: Administration of 0.9% NaCl solution, Other: Measurement of stroke volume, Other: Measurement of microvascular blood flowVolunteers receiving 0.9% NaCl to optimise stroke volume |
| Volunteers receiving gelofusine | – | Other: Measurement of stroke volume, Other: Measurement of microvascular blood flow, Other: Administration of gelofusineVolunteers receiving gelofusine to optimise stroke volume |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy male volunteers, aged 18-80.
Key inclusion criteria (3 listed)
- male
- age 18-80 years
- body mass index 20-30kg/m2
Key exclusion criteria (14 listed)
- BMI < 20 or > 30 kg/m2.
- Active cardiovascular disease: uncontrolled hypertension (BP > 160/100), angina, heart failure (class III/IV), arhythmias , right to left cardiac shunt or recent cardiac event.
- Individuals taking beta-adrenergic blocking agents.
- Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial)..
- Metabolic disease: hyper and hypo parathyroidism, untreated hyper and hypothyroidism, Cushing's disease, types 1 or 2 diabetes.
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 |
|---|---|---|
| Administration of 0.9% NaCl solutionAlso: Normal saline, SalineVolunteers administered 0.9% NaCl solution in 250ml boluses | Other | Volunteers receiving 0.9% NaCl |
| Measurement of stroke volumeThe measurement of stroke volume will be performed using an Oesophageal Doppler Monitor. | Other | Volunteers receiving 0.9% NaCl, Volunteers receiving gelofusine |
| Measurement of microvascular blood flowAlso: CEUS, Contrast enhanced ultrasound scan, SonoVue.Microvascular blood flow will be measured using a contrast enhanced ultrasound scan. | Other | Volunteers receiving 0.9% NaCl, Volunteers receiving gelofusine |
| Administration of gelofusineVolunteers administered gelofusine in 250ml boluses | Other | Volunteers receiving gelofusine |
Primary outcome
Change in microvascular visceral blood flow
Time frame: 30 minutes
Microvascular visceral blood flow is assessed using contrast enhanced ultrasound scanning, following stroke volume optimisation.
2 secondary outcomes
Change in stroke volume
Time frame: 30 minutes
Change in haematocrit
Time frame: 60 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 27 Jan 2015.
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Screening Protocol
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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.
John P Williams, PhD principal investigator
University of Nottingham
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 Healthy Volunteers, run by University of Nottingham at 1 site in United Kingdom.
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 14 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 27 Jan 2015. 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 United Kingdom. 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?
Change in microvascular visceral blood flow (time frame: 30 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 27 Jan 2015.