Quantitative Assessment and Characterization of Microvascular Function Using Diffuse Optical Tomography

NCT03411213 | Completed

• 1 other identifier: STH18094
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Atherosclerosis is accompanied by microvascular dysfunction (an impairment of blood vessels to dilate or constrict in response to demand). The ability to reliably measure microvascular dysfunction would help identify patients at risk of myocardial infarction and test new treatments. All existing measures of microvascular dysfunction suffer significant limitations. Near Infrared Spectroscopy (NIRS) is an imaging method that uses an infrared light-source and detector (called optodes) to painlessly shines light into tissue and collect reflected light at different wavelengths. This data allows quantification of the amount of haemoglobin (blood) in the tissue and whether it is oxygenated or de-oxygenated. Diffuse optical tomography (DOT) is a powerful analysis technique for data collected from multiple NIRH optodes. Unlike most NIRS studies that use a single pair of optodes and collects a single datapoint for each wavelength over time, DOT allows three-dimensional spatial reconstruction of haemodynamic and anatomic changes in a large region of tissue over time. In preliminary work DOT had the potential to measure forearm reactive hyperaemia, a key indicator of microvascular function. Team will test whether DOT can detect differences between patients and healthy volunteers. In this work, 30 patients will be recruited with type 2 diabetes, 30 patients who have had a previous myocardial infarction and 30 healthy volunteers. The Investigator will also recruit 50 patients who are on waiting lists for coronary angiography. The DOT will be used to measure participants' microvascular function after brachial artery occlusion by a blood pressure cuff. The Investigator will then examine whether DOT can detect differences between healthy volunteers, diabetics, and patients with a previous heart attack, and whether DOT is able to predict existence of coronary artery disease on angiography. If successful, DOT can be developed for assessment of microvascular function to the point where it could be applied to clinical studies.

Conditions

Atherosclerosis; Diabetes; Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• Can diffuse optical tomography detect microvascular function?

  Measuring microvascular function with diffuse optical tomography

  3 years from start date

Secondary Outcomes (3)

• Detecting differences in microvascular function in atherosclerosis

  3 years from start date

• Detecting differences in microvascular function in diabetes

  3 years from start date

• Predicting coronary artery disease before angiography

  3 years from start date

Study Arms (2)

Vascular function

EXPERIMENTAL

Diffuse optical tomography detection of differences in vascular function between healthy volunteers and patients with proven heart disease or diabetes.

Device: diffuse optical tomography

Coronary artery disease

EXPERIMENTAL

Diffuse optical tomography prediction of presence or severity of coronary artery disease on angiography.

Device: diffuse optical tomography

Interventions

diffuse optical tomography DEVICE

Optical tomography is a form of computed tomography that creates a digital volumetric model of an object by reconstructing images made from light transmitted and scattered through an object.

Coronary artery disease; Vascular function

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-80 of either sex
• Ability to read and speak English to a level allowing understanding of the patient information and to give consent to participate
• Diagnosed as type 2 diabetic for at least 12 months
• No painful arms or health problems preventing blood pressure cuff inflation
• No lymphoedema of the arm
• Not diabetic or known to have suffered a myocardial infarction in the past

You may not qualify if:

• Any patients that do not meet the above criteria will be excluded

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust: lead
• University of Sheffield: collaborator

Study Sites (1)

Northern General Hospital

Sheffield, South Yorkshire, S5 7AU, United Kingdom

Location

Related Publications (10)

• Marzilli M, Merz CN, Boden WE, Bonow RO, Capozza PG, Chilian WM, DeMaria AN, Guarini G, Huqi A, Morrone D, Patel MR, Weintraub WS. Obstructive coronary atherosclerosis and ischemic heart disease: an elusive link! J Am Coll Cardiol. 2012 Sep 11;60(11):951-6. doi: 10.1016/j.jacc.2012.02.082.

  PMID: 22954239 BACKGROUND

• Tooke JE. Microvascular function in human diabetes. A physiological perspective. Diabetes. 1995 Jul;44(7):721-6. doi: 10.2337/diab.44.7.721.

  PMID: 7789639 BACKGROUND

• Pyke KE, Tschakovsky ME. Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation? J Appl Physiol (1985). 2007 Apr;102(4):1510-9. doi: 10.1152/japplphysiol.01024.2006. Epub 2006 Dec 14.

  PMID: 17170205 BACKGROUND

• Charakida M, Masi S, Luscher TF, Kastelein JJ, Deanfield JE. Assessment of atherosclerosis: the role of flow-mediated dilatation. Eur Heart J. 2010 Dec;31(23):2854-61. doi: 10.1093/eurheartj/ehq340. Epub 2010 Sep 23.

  PMID: 20864485 BACKGROUND

• Huang AL, Silver AE, Shvenke E, Schopfer DW, Jahangir E, Titas MA, Shpilman A, Menzoian JO, Watkins MT, Raffetto JD, Gibbons G, Woodson J, Shaw PM, Dhadly M, Eberhardt RT, Keaney JF Jr, Gokce N, Vita JA. Predictive value of reactive hyperemia for cardiovascular events in patients with peripheral arterial disease undergoing vascular surgery. Arterioscler Thromb Vasc Biol. 2007 Oct;27(10):2113-9. doi: 10.1161/ATVBAHA.107.147322. Epub 2007 Aug 23.

  PMID: 17717291 BACKGROUND

• Mitchell GF, Parise H, Vita JA, Larson MG, Warner E, Keaney JF Jr, Keyes MJ, Levy D, Vasan RS, Benjamin EJ. Local shear stress and brachial artery flow-mediated dilation: the Framingham Heart Study. Hypertension. 2004 Aug;44(2):134-9. doi: 10.1161/01.HYP.0000137305.77635.68. Epub 2004 Jul 12.

  PMID: 15249547 BACKGROUND

• Rubinshtein R, Kuvin JT, Soffler M, Lennon RJ, Lavi S, Nelson RE, Pumper GM, Lerman LO, Lerman A. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J. 2010 May;31(9):1142-8. doi: 10.1093/eurheartj/ehq010. Epub 2010 Feb 24.

  PMID: 20181680 BACKGROUND

• Bonetti PO, Pumper GM, Higano ST, Holmes DR Jr, Kuvin JT, Lerman A. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol. 2004 Dec 7;44(11):2137-41. doi: 10.1016/j.jacc.2004.08.062.

  PMID: 15582310 BACKGROUND

• Dhawan AP, D'Alessandro B, Fu X. Optical imaging modalities for biomedical applications. IEEE Rev Biomed Eng. 2010;3:69-92. doi: 10.1109/RBME.2010.2081975.

  PMID: 22275202 BACKGROUND

• Takagishi Y, Yamamura H. Purkinje cell abnormalities and synaptogenesis in genetically jaundiced rats (Gunn rats). Brain Res. 1989 Jul 17;492(1-2):116-28. doi: 10.1016/0006-8993(89)90894-9.

  PMID: 2752293 BACKGROUND

MeSH Terms

Conditions

Atherosclerosis; Diabetes Mellitus; Coronary Artery Disease

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases

Study Officials

• Timothy Chico

  University of Sheffield

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: January 26, 2018
• Study Start: January 11, 2016
• Primary Completion: March 26, 2020
• Study Completion: March 26, 2020
• Last Updated: May 17, 2022

Record last verified: 2022-05

Locations

GB (1)