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Doppler Ultrasound Investigation of Microcirculations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01045005
Recruitment Status : Withdrawn
First Posted : January 8, 2010
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Queen's University, Belfast

Tracking Information
First Submitted Date  ICMJE January 6, 2010
First Posted Date  ICMJE January 8, 2010
Last Update Posted Date August 20, 2019
Study Start Date  ICMJE January 2006
Actual Primary Completion Date July 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 7, 2010)
Doppler Blood flow velocity waveforms measured at rest and after administration of oxygen and carbon dioxide [ Time Frame: At initial visit and then yearly ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01045005 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2010)
Radial Artery pressure waveforms [ Time Frame: At initial visit and then yearly ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Doppler Ultrasound Investigation of Microcirculations
Official Title  ICMJE Doppler Ultrasound Investigation of Ocular and Skeletal Microcirculations in Health and Disease
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Type 1 Diabetes Mellitus
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • Active Comparator: Type 1 Diabetes
    Subjects with type 1 diabetes mellitus who are administered oxygen and carbon dioxide
    Intervention: Other: Administration of Oxygen and carbon dioxide
  • Active Comparator: Control Subjects
    Healthy volunteers administered oxygen and carbon dioxide via respiratory apparatus
    Intervention: Other: Administration ofOxygen and carbon dioxide
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: August 16, 2019)
0
Original Estimated Enrollment  ICMJE
 (submitted: January 7, 2010)
72
Actual Study Completion Date  ICMJE July 2010
Actual Primary Completion Date July 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01045005
Other Study ID Numbers  ICMJE 05060CL−A
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Queen's University, Belfast
Study Sponsor  ICMJE Queen's University, Belfast
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Gary E McVeigh, MD PhD FRCP Queens University Belfast
PRS Account Queen's University, Belfast
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP