Doppler Ultrasound Investigation of Microcirculations

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2008 by Queen's University, Belfast.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Queen's University, Belfast
ClinicalTrials.gov Identifier:
NCT01045005
First received: January 6, 2010
Last updated: January 7, 2010
Last verified: January 2008
  Purpose

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.


Condition Intervention
Type 1 Diabetes Mellitus
Other: Administration ofOxygen and carbon dioxide
Other: Administration of Oxygen and carbon dioxide

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Doppler Ultrasound Investigation of Ocular and Skeletal Microcirculations in Health and Disease

Resource links provided by NLM:


Further study details as provided by Queen's University, Belfast:

Primary Outcome Measures:
  • Doppler Blood flow velocity waveforms measured at rest and after administration of oxygen and carbon dioxide [ Time Frame: At initial visit and then yearly ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radial Artery pressure waveforms [ Time Frame: At initial visit and then yearly ] [ Designated as safety issue: No ]

Estimated Enrollment: 72
Study Start Date: January 2006
Estimated Study Completion Date: May 2011
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Type 1 Diabetes
Subjects with type 1 diabetes mellitus who are administered oxygen and carbon dioxide
Other: Administration of Oxygen and carbon dioxide
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.
Active Comparator: Control Subjects
Healthy volunteers administered oxygen and carbon dioxide via respiratory apparatus
Other: Administration ofOxygen and carbon dioxide
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01045005

Contacts
Contact: Gary E McVeigh, MD PhD FRCP +442890 974772 g.mcveigh@qub.ac.uk

Locations
United Kingdom
Department of Therapeutics and Pharmacology, Queens University Belfast Recruiting
Belfast, Antrim, United Kingdom, BT9 7RL
Contact: Gary E McVeigh, MD PhD FRCP    +442890 974772    g.mcveigh@qub.ac.uk   
Principal Investigator: Gary E McVeigh, MD PhD FRCP         
Sub-Investigator: Mark T Harbinson, MD FRCP         
Sponsors and Collaborators
Queen's University, Belfast
Investigators
Principal Investigator: Gary E McVeigh, MD PhD FRCP Queens University Belfast
  More Information

Publications:
Responsible Party: Professor Gary McVeigh, Department of Therapeutics and Pharmacology, Queens University Belfast
ClinicalTrials.gov Identifier: NCT01045005     History of Changes
Other Study ID Numbers: 05060CL−A
Study First Received: January 6, 2010
Last Updated: January 7, 2010
Health Authority: United Kingdom: Department of Health

Keywords provided by Queen's University, Belfast:
Type 1 diabetes
Endothelial dysfunction
Doppler Ultrasound Velocity Waveforms

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on October 16, 2014