Doppler Ultrasound Investigation of Microcirculations

August 16, 2019 updated by: Queen's University, Belfast

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Antrim
      • Belfast, Antrim, United Kingdom, BT9 7RL
        • Department of Therapeutics and Pharmacology, Queens University Belfast

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Doppler Blood flow velocity waveforms measured at rest and after administration of oxygen and carbon dioxide
Time Frame: At initial visit and then yearly
At initial visit and then yearly

Secondary Outcome Measures

Outcome Measure
Time Frame
Radial Artery pressure waveforms
Time Frame: At initial visit and then yearly
At initial visit and then yearly

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Queen's University, Belfast

Investigators

  • Principal Investigator: Gary E McVeigh, MD PhD FRCP, Queens University Belfast

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

July 1, 2010

Study Completion (Actual)

July 1, 2010

Study Registration Dates

First Submitted

January 6, 2010

First Submitted That Met QC Criteria

January 7, 2010

First Posted (Estimate)

January 8, 2010

Study Record Updates

Last Update Posted (Actual)

August 20, 2019

Last Update Submitted That Met QC Criteria

August 16, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05060CL-A

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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