Type 1 Diabetes MellitusNCT01045005
Doppler Ultrasound Investigation of Microcirculations
A study testing Administration ofOxygen and carbon dioxide and Administration of Oxygen and carbon dioxide in people with Type 1 Diabetes Mellitus, run by Queen's University, Belfast at 1 site in United Kingdom.
Trial summary
The investigators aim to show that quantitative analysis of doppler flow velocity waveforms i.e. ultrasound which is a non-invasive and very safe means of assessing blood flow; recorded in the proximity of terminal microvascular beds of interest, (i.e. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Administration ofOxygen and carbon dioxide and Administration of Oxygen and carbon dioxide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2006to Jul 2010
- Phase
- Interventional
- 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
Who may be able to join
- To be eligible for study patients must be older than 18 years.
- All patients will have undergone an extensive clinical evaluation performed at the Belfast City Hospital diabetes clinic that includes retinal photography.
- Patients will be eligible for the study if they are in stable control of their diabetes with a haemoglobin of A1c between 6.5 and 10%.
- Patients will be eligible if they have background retinopathy. The control subjects will be healthy individuals; and will be age and sex matched for the disease population.
Who cannot join
- Patients with proliferative retinopathy or those undergoing laser therapy will be excluded from study. This would make assessment of the retinal arteriolar structure very difficult.
- Patients will also be excluded if they have hypertension (a blood pressure >140/90mmHg) or taking antihypertensive drugs. The investigators know that the presence of hypertension will have an effect on the retinal waveforms and structure.
- Patients will also be excluded if they have any significant renal disease (GFR <60ml min) or a history of cardiovascular or cerebrovascular complications.
- Patients with microalbuminuria (>3 g/min) can be included in the study but would be asked to stop their medication (e.g. ACE inhibitor) for 5 days prior to the study period. It should be mentioned that the risk associated with stopping this effective medication for such a period of time is minimal. This has been common practice in our department in a number of previous studies, and in the published literature. This will be clearly communicated to the patient in the patient information sheet, in the patient consent form; and in the discussion/process of obtaining informed consent with the patient
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Department of Therapeutics and Pharmacology, Queens University Belfast
Belfast, Antrim, BT9 7RL
About this study
Official title: Doppler Ultrasound Investigation of Ocular and Skeletal Microcirculations in Health and Disease
The investigators aim to show that quantitative analysis of doppler flow velocity waveforms i.e. ultrasound which is a non-invasive and very safe means of assessing blood flow; recorded in the proximity of terminal microvascular beds of interest, (i.e. the forearm and ocular circulation) can sensitively detect and track local changes in microvascular haemodynamics i.e. the function of the small blood vessels that are found in the back of the eye and in the forearm.
The investigators also aim to relate change in the doppler spectral flow velocity waveform i.e. the ultrasound signal, in the central retinal artery to changes in geometry and tone of the vasculature (or changes in the structure and function of small blood vessels) in response to inhaled oxygen and carbon dioxide. The geometry and tone of the vasculature (or Blood Vessels) can be measured by taking photographs of the back of the eye.
Read the detailed description
Diabetes mellitus significantly increases the risk for both small and large blood vessel complications e.g. diabetic eye problems and coronary heart disease. Vital organs such as the eye, kidney, heart and brain represent well- recognized preferential targets in patients with diabetes mellitus. The presence of such end-organ damage powerfully influences cardiovascular risk and the benefits of therapeutic interventions. Unfortunately, by the time symptoms develop or events occur as manifestations of target-organ damage, the disease process is already at an advanced stage. Although not traditionally viewed as an end-organ, it is altered structure and function of arterial small blood vessels that acts as the substrate for accelerated disease development and the increased occurrence of vascular events in patients with diabetes mellitus. The ability to detect and monitor sub-clinical damage, representing the cumulative and integrated influence of all risk factors in impairing arterial wall integrity, holds potential to further refine cardiovascular risk stratification and enable early intervention to prevent or attenuate disease progression.
Data derived from analysis of arterial waveforms, that marks the presence of impaired pulsatile function in the arterial system, has been shown to predict future cardiovascular risk. As consistent abnormalities in the arterial pulse wave shape have been recognized for many years in diabetic subjects there has been a growing interest in quantifying changes in the pulse contour to provide information about the status of the vasculature in diabetes. These original observations have been confirmed in more recent studies in patients with type 1 and type 2 diabetes mellitus and are detected prior to the development of clinical complications of the disease.
Analysis of the pulse contours recorded from sites in large conduit arteries identify structural and functional abnormalities predominantly in the systemic microvasculature, as small arteries and arterioles are recognised as the major sites for wave reflection that alters pulse contour morphology. It is recognised that techniques providing a global assessment of the circulation may not capture and cannot localise findings to a specific site or target-organ of interest in the arterial system. Microcirculation is a collective term for the smallest segments of the vascular system and is a major site of control of vascular resistance. It includes arterioles and capillaries and is considered to be a continuum rather than a distinct site of resistance control. Importantly, it is recognised as sites were the earliest manifestations of cardiovascular disease, especially inflammatory processes occur. The microvasculature may therefore constitute a preferential target or be primarily involved in the pathogenesis of disease and represents an important regional target for therapeutic interventions. Further, retinal photography and standardised grading provides a unique opportunity to study retinal microvascular characteristics including retinopathy and change in arteriolar (or blood vessel) structure and function. Improved methods of assessment to study the retinal microvascular network holds potential to improve prediction of risk, identify high risk groups and act as a window to monitor the effects of possible drug interventions.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Administration ofOxygen and carbon dioxide, Administration of Oxygen and carbon dioxide
- Keywords
- Type 1 diabetes, Endothelial dysfunction, Doppler Ultrasound Velocity Waveforms
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Administration ofOxygen and carbon dioxideOther
Inhalation of 100% oxygen and 4% carbon dioxide. This is non-harmful/non-toxic and will be given according to protocol previously described in the literature. It will be administered for a maximum of 4 minutes.
Administration of Oxygen and carbon dioxideOther
Inhalation of 100% oxygen and 4% carbon dioxide. This is non-harmful/non-toxic and will be given according to protocol previously described in the literature. It will be administered for a maximum of 4 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Type 1 Diabetes | Active comparator | Subjects with type 1 diabetes mellitus who are administered oxygen and carbon dioxide Receives: Other: Administration of Oxygen and carbon dioxide |
| Control Subjects | Active comparator | Healthy volunteers administered oxygen and carbon dioxide via respiratory apparatus Receives: Other: Administration ofOxygen and carbon dioxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Doppler Blood flow velocity waveforms measured at rest and after administration of oxygen and carbon dioxide
Measured: At initial visit and then yearly
Secondary outcomes (1)
Radial Artery pressure waveforms
Measured: At initial visit and then yearly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2010 (estimated)
- Study startJan 2006
- Primary completionJul 2010
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen's University, Belfast
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gary E McVeigh, MD PhD FRCP, Principal investigator, Queens University Belfast
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01045005
- Sponsor's protocol ID
- 05060CL-A
- Status last verified
- Aug 2019
- First submitted
- 6 Jan 2010
- Last updated
- 20 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wright SA, O'Prey FM, Hamilton PK, Lockhart CJ, McCann A, McHenry MT, McGivern RC, Plumb R, Finch MB, Bell AL, McVeigh GE. Colour Doppler ultrasound of the ocular circulation in patients with systemic lupus erythematosus identifies altered microcirculatory haemodynamics. Lupus. 2009 Oct;18(11):950-7. doi: 10.1177/0961203309104865.
PubMed 19762395Agnew CE, Rea DJ, McCann AJ, Lockhart CJ, Hamilton PK, Quinn CE, McVeigh GE, McGivern RC. Root-MUSIC analysis of nitric oxide-mediated changes in ophthalmic artery blood flow velocity waveforms. Med Eng Phys. 2009 Sep;31(7):799-805. doi: 10.1016/j.medengphy.2009.03.003. Epub 2009 Apr 16.
PubMed 19375374Lockhart CJ, Hamilton PK, Quinn CE, McVeigh GE. End-organ dysfunction and cardiovascular outcomes: the role of the microcirculation. Clin Sci (Lond). 2009 Feb;116(3):175-90. doi: 10.1042/CS20080069.
PubMed 19118490Lockhart CJ, Hamilton PK, McVeigh KA, McVeigh GE. A cardiologist view of vascular disease in diabetes. Diabetes Obes Metab. 2008 Apr;10(4):279-92. doi: 10.1111/j.1463-1326.2007.00727.x. Epub 2007 Oct 15.
PubMed 17941877Hamilton PK, Lockhart CJ, Quinn CE, McVeigh GE. Arterial stiffness: clinical relevance, measurement and treatment. Clin Sci (Lond). 2007 Aug;113(4):157-70. doi: 10.1042/CS20070080.
PubMed 17623012Lockhart CJ, Gamble AJ, Rea D, Hughes S, McGivern RC, Wolsley C, Stevenson M, Harbinson MT, Plumb RD, McVeigh GE. Nitric oxide modulation of ophthalmic artery blood flow velocity waveform morphology in healthy volunteers. Clin Sci (Lond). 2006 Jul;111(1):47-52. doi: 10.1042/CS20050365.
PubMed 16499475
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Doppler Ultrasound Investigation of Ocular and Skeletal Microcirculations in Health and Disease
- ClinicalTrials.gov ID
- NCT01045005
- Acronym / sponsor ID
- 05060CL-A
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Type 1 diabetes, Endothelial dysfunction, Doppler Ultrasound Velocity Waveforms
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Queen's University, BelfastUniversity, hospital or other
- Study start
- Jan 2006
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 8 Jan 2010 (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.
The investigators aim to show that quantitative analysis of doppler flow velocity waveforms i.e. ultrasound which is a non-invasive and very safe means of assessing blood flow; recorded in the proximity of terminal microvascular beds of interest, (i.e. the forearm and ocular circulation) can sensitively detect and track local changes in microvascular haemodynamics i.e. the function of the small blood vessels that are found in the back of the eye and in the forearm.
The investigators also aim to relate change in the doppler spectral flow velocity waveform i.e. the ultrasound signal, in the central retinal artery to changes in geometry and tone of the vasculature (or changes in the structure and function of small blood vessels) in response to inhaled oxygen and carbon dioxide. The geometry and tone of the vasculature (or Blood Vessels) can be measured by taking photographs of the back of the eye.
Detailed description
Diabetes mellitus significantly increases the risk for both small and large blood vessel complications e.g. diabetic eye problems and coronary heart disease. Vital organs such as the eye, kidney, heart and brain represent well- recognized preferential targets in patients with diabetes mellitus. The presence of such end-organ damage powerfully influences cardiovascular risk and the benefits of therapeutic interventions. Unfortunately, by the time symptoms develop or events occur as manifestations of target-organ damage, the disease process is already at an advanced stage. Although not traditionally viewed as an end-organ, it is altered structure and function of arterial small blood vessels that acts as the substrate for accelerated disease development and the increased occurrence of vascular events in patients with diabetes mellitus. The ability to detect and monitor sub-clinical damage, representing the cumulative and integrated influence of all risk factors in impairing arterial wall integrity, holds potential to further refine cardiovascular risk stratification and enable early intervention to prevent or attenuate disease progression.
Data derived from analysis of arterial waveforms, that marks the presence of impaired pulsatile function in the arterial system, has been shown to predict future cardiovascular risk. As consistent abnormalities in the arterial pulse wave shape have been recognized for many years in diabetic subjects there has been a growing interest in quantifying changes in the pulse contour to provide information about the status of the vasculature in diabetes. These original observations have been confirmed in more recent studies in patients with type 1 and type 2 diabetes mellitus and are detected prior to the development of clinical complications of the disease.
Analysis of the pulse contours recorded from sites in large conduit arteries identify structural and functional abnormalities predominantly in the systemic microvasculature, as small arteries and arterioles are recognised as the major sites for wave reflection that alters pulse contour morphology. It is recognised that techniques providing a global assessment of the circulation may not capture and cannot localise findings to a specific site or target-organ of interest in the arterial system. Microcirculation is a collective term for the smallest segments of the vascular system and is a major site of control of vascular resistance. It includes arterioles and capillaries and is considered to be a continuum rather than a distinct site of resistance control. Importantly, it is recognised as sites were the earliest manifestations of cardiovascular disease, especially inflammatory processes occur. The microvasculature may therefore constitute a preferential target or be primarily involved in the pathogenesis of disease and represents an important regional target for therapeutic interventions. Further, retinal photography and standardised grading provides a unique opportunity to study retinal microvascular characteristics including retinopathy and change in arteriolar (or blood vessel) structure and function. Improved methods of assessment to study the retinal microvascular network holds potential to improve prediction of risk, identify high risk groups and act as a window to monitor the effects of possible drug interventions.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Type 1 Diabetes | Active comparator | Other: Administration of Oxygen and carbon dioxideSubjects with type 1 diabetes mellitus who are administered oxygen and carbon dioxide |
| Control Subjects | Active comparator | Other: Administration ofOxygen and carbon dioxideHealthy volunteers administered oxygen and carbon dioxide via respiratory apparatus |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- To be eligible for study patients must be older than 18 years.
- All patients will have undergone an extensive clinical evaluation performed at the Belfast City Hospital diabetes clinic that includes retinal photography.
- Patients will be eligible for the study if they are in stable control of their diabetes with a haemoglobin of A1c between 6.5 and 10%.
- Patients will be eligible if they have background retinopathy. The control subjects will be healthy individuals; and will be age and sex matched for the disease population.
Key exclusion criteria (4 listed)
- Patients with proliferative retinopathy or those undergoing laser therapy will be excluded from study. This would make assessment of the retinal arteriolar structure very difficult.
- Patients will also be excluded if they have hypertension (a blood pressure >140/90mmHg) or taking antihypertensive drugs. The investigators know that the presence of hypertension will have an effect on the retinal waveforms and structure.
- Patients will also be excluded if they have any significant renal disease (GFR <60ml min) or a history of cardiovascular or cerebrovascular complications.
- Patients with microalbuminuria (>3 g/min) can be included in the study but would be asked to stop their medication (e.g. ACE inhibitor) for 5 days prior to the study period. It should be mentioned that the risk associated with stopping this effective medication for such a period of time is minimal. This has been common practice in our department in a number of previous studies, and in the published literature. This will be clearly communicated to the patient in the patient information sheet, in the patient consent form; and in the discussion/process of obtaining informed consent with the patient
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 ofOxygen and carbon dioxideInhalation of 100% oxygen and 4% carbon dioxide. This is non-harmful/non-toxic and will be given according to protocol previously described in the literature. It will be administered for a maximum of 4 minutes. | Other | Control Subjects |
| Administration of Oxygen and carbon dioxideInhalation of 100% oxygen and 4% carbon dioxide. This is non-harmful/non-toxic and will be given according to protocol previously described in the literature. It will be administered for a maximum of 4 minutes. | Other | Type 1 Diabetes |
Primary outcome
Doppler Blood flow velocity waveforms measured at rest and after administration of oxygen and carbon dioxide
Time frame: At initial visit and then yearly
1 secondary outcome
Radial Artery pressure waveforms
Time frame: At initial visit and then yearly
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2019.
- Background: PubMed 19762395Wright SA, O'Prey FM, Hamilton PK, Lockhart CJ, McCann A, McHenry MT, McGivern RC, Plumb R, Finch MB, Bell AL, McVeigh GE. Colour Doppler ultrasound of the ocular circulation in patients with systemic lupus erythematosus identifies altered microcirculatory haemodynamics. Lupus. 2009 Oct;18(11):950-7. doi: 10.1177/0961203309104865.
- Background: PubMed 19375374Agnew CE, Rea DJ, McCann AJ, Lockhart CJ, Hamilton PK, Quinn CE, McVeigh GE, McGivern RC. Root-MUSIC analysis of nitric oxide-mediated changes in ophthalmic artery blood flow velocity waveforms. Med Eng Phys. 2009 Sep;31(7):799-805. doi: 10.1016/j.medengphy.2009.03.003. Epub 2009 Apr 16.
- Background: PubMed 19118490Lockhart CJ, Hamilton PK, Quinn CE, McVeigh GE. End-organ dysfunction and cardiovascular outcomes: the role of the microcirculation. Clin Sci (Lond). 2009 Feb;116(3):175-90. doi: 10.1042/CS20080069.
- Background: PubMed 17941877Lockhart CJ, Hamilton PK, McVeigh KA, McVeigh GE. A cardiologist view of vascular disease in diabetes. Diabetes Obes Metab. 2008 Apr;10(4):279-92. doi: 10.1111/j.1463-1326.2007.00727.x. Epub 2007 Oct 15.
- Background: PubMed 17623012Hamilton PK, Lockhart CJ, Quinn CE, McVeigh GE. Arterial stiffness: clinical relevance, measurement and treatment. Clin Sci (Lond). 2007 Aug;113(4):157-70. doi: 10.1042/CS20070080.
- Background: PubMed 16499475Lockhart CJ, Gamble AJ, Rea D, Hughes S, McGivern RC, Wolsley C, Stevenson M, Harbinson MT, Plumb RD, McVeigh GE. Nitric oxide modulation of ophthalmic artery blood flow velocity waveform morphology in healthy volunteers. Clin Sci (Lond). 2006 Jul;111(1):47-52. doi: 10.1042/CS20050365.
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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.
Gary E McVeigh, MD PhD FRCP principal investigator
Queens University Belfast
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Administration ofOxygen and carbon dioxide and Administration of Oxygen and carbon dioxide in people with Type 1 Diabetes Mellitus, run by Queen's University, Belfast 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 4 inclusion and 4 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: withdrawn, as of the sponsor's last update on 20 Aug 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 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 was withdrawn before enrolling participants, so there are no results.
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?
Doppler Blood flow velocity waveforms measured at rest and after administration of oxygen and carbon dioxide (time frame: At initial visit and then yearly). 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 NCT01045005, which also lists 6 linked publications.
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 20 Aug 2019.