Progression of Coronary Atherosclerosis in Asymptomatic Diabetic Subjects

NCT ID: NCT02109835

Last Updated: 2015-05-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

250 participants

Study Classification

OBSERVATIONAL

Study Start Date

2012-09-30

Study Completion Date

2017-07-31

Brief Summary

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The purpose of the study is to identify a sub-group of diabetic patients at higher risk of progression of coronary disease and also more likely to suffer from heart attack/angina and heart failure. The total number of patients to be recruited in this study will be 250 with type-2 diabetes but no known heart disease. These patients will have an objective measure of the function of the lining of the arteries, CT scan of the arteries of the heart and an ultrasound scan of the heart and arteries of the neck done at baseline along with blood tests for identification new markers of malfunction of the lining and inflammation of the arteries. Patients will be followed up at 18 months. During the follow-up visit, in addition to the blood tests, the CT scan of the heart arteries and ultrasound of the heart and arteries of the neck will be repeated to assess progression of the non-calcified, calcified and mixed plaques in the coronary arteries.

Detailed Description

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Hypothesis: We hypothesise that a combination of CT coronary angiography, ultrasound of the heart and of the arteries of the neck, evaluation of expression of genetic markers and bio-markers in the blood will help identify diabetic patients at highest risk of heart disease progression,that can result in angina, heart attacks, heart failure and cardiovascular deaths.

Previous studies using coronary calcium scanning in diabetic patients showed that those with the greatest progression in calcified plaque in the coronary arteries were at the highest risk for heart attacks. However, coronary calcium scans only identify the calcified plaque and are not able to pick up non-calcified, cholesterol rich plaques. Cholesterol rich non-calcified plaques are more often associated witn acute heart attacks. CT coronary angiography can identify both calcified and non-calcified plaques and can therefore add significantly to our predictive ability. Certain chemical substances (biomarkers) measured in blood indicate the severity of plaque burden and inflammation in the coronary arteries. A combination of CT coronary angiography, expression of genetic markers, measure of function of the cells lining the blood vessels and biomarkers can help to identify diabetic patients at highest risk of heart attacks, allowing us to start appropriate risk reduction treatments in those patients. In previous studies with coronary artery calcium, patients suffering from heart attacks were those who also had a higher progression of coronary artery calcium (CAC) score. In diabetics, in particular, patients with poor control of their blood glucose also had greater progression of the CAC score. In order to test the validity of our hypothesis, we have decided to base our study on a population of established diabetics with difficult to control blood pressure, high cholesterol and chronic complications of the small blood vessels, i.e. involvement of the retina (back of the eye) and peripheral nerves as well as protein in the urine. Patients with chronic complications of diabetes are known to have higher incidence of heart disease as well.

Methodology and Timetable: Patients will be recruited from Diabetes clinics of NHS hospitals in North West London.

If eligible for the trial, an informed consent will be obtained from the patients and their general practitioner will be subsequently informed about their participation in the trial. Once recruited into the trial, a CT coronary angiogram (CTCA, CT of the arteries of the heart), ultrasound scan of the heart and carotid arteries of the neck as well as a measure of endothelial function will be performed at the Wellington Hospital in St. Johns Wood, London within 1-2 weeks. At the same time, blood samples will also be obtained for bio-markers. A report of the CTCA will then be forwarded to the consultant in-charge of the patient's care as well as to the GP.

If a narrowing of moderate degree (70%) is noted on the CT angiogram, the patient will then be brought back to the Wellington Hospital within 2 weeks for a heart perfusion scan which evaluates the relative discrepancies in flow of blood to the heart muscle and helps plan further management.

If there is significant reduction in blood flow noted in the perfusion scan,patients will be referred back to the consultants for further clinical management.

During their first visit to the Wellington Hospital for the CT scan, blood samples will be taken and stored on-site for biomarker analysis.

Patients will be followed up after 18 months from the time of recruitment into the trial,when a second CTCA, ultrasound of the arteries of the neck will be performed to assess the degree of progression of calcium and cholesterol deposits within the coronary arteries and thickness of the lining of the arteries in the neck in addition to blood sample collection for bio-markers.

Patients with significant narrowing of coronary arteries (\>70%) requiring a stent to be inserted in the first scan will be excluded from follow up. Patients with normal coronary arteries on the initial scan also will be excluded from the follow-up.

Conditions

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Type 2 Diabetes Coronary Artery Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Asymptomatic type 2 diabetes

Patients without previous history of coronary artery disease

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Established T2DM with or without micro-vascular complications of diabetes (retinopathy, peripheral neuropathy and/or micro-albuminuria)

No history of coronary artery disease (CAD)

Exclusion Criteria

* 1\. Estimated GFR \<45 2. Pregnant women 3. Age \< 35 years 4. Atrial fibrillation 5. Known allergy to iodine contrast 6. CAC score \>1000 Agatston Units
Minimum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Royal Free Hospital NHS Foundation Trust

OTHER

Sponsor Role collaborator

London North West Healthcare NHS Trust

OTHER

Sponsor Role collaborator

Barnet and Chase Farm Hospitals NHS Trust

OTHER

Sponsor Role collaborator

Diabetes and Obesity Research Network

NETWORK

Sponsor Role collaborator

Lund University

OTHER

Sponsor Role collaborator

Health Diagnostic Laboratory, Inc.

INDUSTRY

Sponsor Role collaborator

British Cardiac Research Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Roby Rakhit, MD FRCP

Role: STUDY_CHAIR

Royal Free Hospital NHS Foundation Trust

Avijit Lahiri, MRCP FACC

Role: STUDY_DIRECTOR

Wellington Hospital

Daniel Darko, MRCP

Role: PRINCIPAL_INVESTIGATOR

Central Middlesex Hospital

Mark Cohen, PhD FRCP

Role: PRINCIPAL_INVESTIGATOR

Barnet Hospital

Rajiv A Amersey, MD FRCP

Role: PRINCIPAL_INVESTIGATOR

Whipps Cross Hospital

Sarita Naik, DM MRCP

Role: PRINCIPAL_INVESTIGATOR

University College London Hospital

Locations

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Central Middlesex Hospital

London, Middlesex, United Kingdom

Site Status RECRUITING

Barts Health NHS Trust

London, , United Kingdom

Site Status NOT_YET_RECRUITING

Barnet Hospital

London, , United Kingdom

Site Status RECRUITING

University College London Hospitals

London, , United Kingdom

Site Status NOT_YET_RECRUITING

Royal Free Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Shreenidhi M Venuraju, MRCP

Role: CONTACT

+442074835062

Anand Jeevarethinam, MRCP

Role: CONTACT

+442074835062

Facility Contacts

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Shreenidhi M Venuraju, MRCP

Role: primary

+442074835062

Shreenidhi M Venuraju, MRCP

Role: primary

+442074835062

Shreenidhi M Venuraju, MRCP

Role: primary

+442074835062

Shreenidhi M Venuraju, MRCP

Role: primary

+442074835062

Shreenidhi M Venuraju, MRCP

Role: primary

+442074835062

References

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Anand DV, Lim E, Lahiri A, Bax JJ. The role of non-invasive imaging in the risk stratification of asymptomatic diabetic subjects. Eur Heart J. 2006 Apr;27(8):905-12. doi: 10.1093/eurheartj/ehi441. Epub 2005 Aug 8.

Reference Type BACKGROUND
PMID: 16087647 (View on PubMed)

Anand DV, Lahiri A, Lim E, Hopkins D, Corder R. The relationship between plasma osteoprotegerin levels and coronary artery calcification in uncomplicated type 2 diabetic subjects. J Am Coll Cardiol. 2006 May 2;47(9):1850-7. doi: 10.1016/j.jacc.2005.12.054. Epub 2006 Apr 19.

Reference Type BACKGROUND
PMID: 16682312 (View on PubMed)

Anand DV, Lim E, Darko D, Bassett P, Hopkins D, Lipkin D, Corder R, Lahiri A. Determinants of progression of coronary artery calcification in type 2 diabetes role of glycemic control and inflammatory/vascular calcification markers. J Am Coll Cardiol. 2007 Dec 4;50(23):2218-25. doi: 10.1016/j.jacc.2007.08.032. Epub 2007 Nov 19.

Reference Type BACKGROUND
PMID: 18061069 (View on PubMed)

Fredrikson GN, Anand DV, Hopkins D, Corder R, Alm R, Bengtsson E, Shah PK, Lahiri A, Nilsson J. Associations between autoantibodies against apolipoprotein B-100 peptides and vascular complications in patients with type 2 diabetes. Diabetologia. 2009 Jul;52(7):1426-33. doi: 10.1007/s00125-009-1377-9. Epub 2009 May 12.

Reference Type BACKGROUND
PMID: 19448981 (View on PubMed)

Jeevarethinam A, Venuraju S, Weymouth M, Atwal S, Lahiri A. Carotid intimal thickness and plaque predict prevalence and severity of coronary atherosclerosis: a pilot study. Angiology. 2015 Jan;66(1):65-9. doi: 10.1177/0003319714522849. Epub 2014 Feb 26.

Reference Type BACKGROUND
PMID: 24576983 (View on PubMed)

Venuraju SM, Lahiri A, Jeevarethinam A, Cohen M, Darko D, Nair D, Rosenthal M, Rakhit RD. Duration of type 2 diabetes mellitus and systolic blood pressure as determinants of severity of coronary stenosis and adverse events in an asymptomatic diabetic population: PROCEED study. Cardiovasc Diabetol. 2019 Apr 23;18(1):51. doi: 10.1186/s12933-019-0855-8.

Reference Type DERIVED
PMID: 31014330 (View on PubMed)

Other Identifiers

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BCRT/3277/PROCEED

Identifier Type: -

Identifier Source: org_study_id

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