Type 2 DiabetesPROCEEDNCT02109835
Progression of Coronary Atherosclerosis in Asymptomatic Diabetic Subjects
An observational study of Type 2 Diabetes and Coronary Artery Disease, run by British Cardiac Research Trust at 5 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Type 2 Diabetes, Coronary Artery Disease
- How many people
- 250 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- Sep 2012to Jul 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with type 2 diabetes recruited from hospital clinics and one community faith based cardiovascular disease prevention clinic run under the aegis of a lipidologist
Who may be able to join
- Established T2DM with or without micro-vascular complications of diabetes (retinopathy, peripheral neuropathy and/or micro-albuminuria)
- No history of coronary artery disease (CAD)
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites, 5 recruiting
- Recruiting
Central Middlesex Hospital
London, Middlesex, NW10 7NS
Shreenidhi M Venuraju, MRCP, +442074835062, shreenidhimv@gmail.com
Daniel Darko, MRCP
- Not yet recruiting
Barts Health NHS Trust
London, EC1A 7BE
Shreenidhi M Venuraju, MRCP, +442074835062, shreenidhimv@gmail.com
Rajiv A Amersey, MD FRCP
- Recruiting
Barnet Hospital
London, EN5 3DJ
Shreenidhi M Venuraju, MRCP, +442074835062, shreenidhimv@gmail.com
Mark Cohen, FRCP PhD
- Not yet recruiting
University College London Hospitals
London, NW1 2BU
Shreenidhi M Venuraju, MRCP, +442074835062, shreenidhimv@gmail.com
Sarita Naik, DM MRCP
- Recruiting
Royal Free Hospital
London, NW3 2QG
Shreenidhi M Venuraju, MRCP, +442074835062, shreenidhimv@gmail.com
Roby Rakhit, MD FRCP
About this study
Official title: Progression of Coronary Atherosclerosis in Asymptomatic Diabetic Subjects: Evaluation of the Role of CT Coronary Angiography and Novel Bio-markers of Endothelial Dysfunction and Vascular Inflammation
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.
Read the detailed description
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
- Type 2 Diabetes, Coronary Artery Disease
- Keywords
- Diabetes, coronary artery disease, Cardiac computed tomography, Computed tomographics coronary angiography, Plaque progression
- Medical subject headings
- Diabetes Mellitus, Type 2, Coronary Artery Disease, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Asymptomatic type 2 diabetes | Patients without previous history of coronary artery disease |
What is being measured
The primary outcome is the main question the study is designed to answer.
Greater than 20% increase in plaque volume
Plaque volume will be measured by both manual and semi-quantitative methods
Measured: 18 months
Secondary outcomes (1)
Greater than 20% increase in coronary artery calcium score
Coronary artery calcium scoring will be performed using a semi-quantitative method.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2014 (estimated)
- Study startSep 2012
- Primary completionJul 2015 (estimated)
- Study completionJul 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- British Cardiac Research Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Free Hospital NHS Foundation Trust, London North West Healthcare NHS Trust, Barnet and Chase Farm Hospitals NHS Trust, Diabetes and Obesity Research Network, Lund University, Health Diagnostic Laboratory, Inc.
- Responsible party
- Sponsor
- Investigators
- Roby Rakhit, MD FRCP, Study chair, Royal Free Hospital NHS Foundation TrustAvijit Lahiri, MRCP FACC, Study director, Wellington HospitalDaniel Darko, MRCP, Principal investigator, Central Middlesex HospitalMark Cohen, PhD FRCP, Principal investigator, Barnet HospitalRajiv A Amersey, MD FRCP, Principal investigator, Whipps Cross HospitalSarita Naik, DM MRCP, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02109835
- Sponsor's protocol ID
- BCRT/3277/PROCEED
- Acronym
- PROCEED
- Status last verified
- May 2015
- First submitted
- 8 Apr 2014
- Last updated
- 19 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 16087647Anand 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.
PubMed 16682312Anand 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.
PubMed 18061069Fredrikson 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.
PubMed 19448981Jeevarethinam 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.
PubMed 24576983Venuraju 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.
PubMed 31014330
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Progression of Coronary Atherosclerosis in Asymptomatic Diabetic Subjects: Evaluation of the Role of CT Coronary Angiography and Novel Bio-markers of Endothelial Dysfunction and Vascular Inflammation
- ClinicalTrials.gov ID
- NCT02109835
- Acronym / sponsor ID
- PROCEED / BCRT/3277/PROCEED
- Conditions
- Type 2 Diabetes, Coronary Artery Disease
- Keywords
- Diabetes, coronary artery disease, Cardiac computed tomography, Computed tomographics coronary angiography, Plaque progression
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- British Cardiac Research TrustUniversity, hospital or other
- Collaborators
- Royal Free Hospital NHS Foundation Trust, London North West Healthcare NHS Trust, Barnet and Chase Farm Hospitals NHS Trust, Diabetes and Obesity Research Network, Lund University, Health Diagnostic Laboratory, Inc.
- Study start
- Sep 2012
- Primary completion
- Jul 2015 (estimated)
- Study completion
- Jul 2017 (estimated)
- First posted
- 10 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Asymptomatic type 2 diabetes | – | –Patients without previous history of coronary artery disease |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with type 2 diabetes recruited from hospital clinics and one community faith based cardiovascular disease prevention clinic run under the aegis of a lipidologist
Key inclusion criteria (2 listed)
- Established T2DM with or without micro-vascular complications of diabetes (retinopathy, peripheral neuropathy and/or micro-albuminuria)
- No history of coronary artery disease (CAD)
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Greater than 20% increase in plaque volume
Time frame: 18 months
Plaque volume will be measured by both manual and semi-quantitative methods
1 secondary outcome
Greater than 20% increase in coronary artery calcium score
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2015.
- Background: PubMed 16087647Anand 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.
- Background: PubMed 16682312Anand 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.
- Background: PubMed 18061069Anand 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.
- Background: PubMed 19448981Fredrikson 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.
- Background: PubMed 24576983Jeevarethinam 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.
- Derived from this study: PubMed 31014330Venuraju 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roby Rakhit, MD FRCP study chair
Royal Free Hospital NHS Foundation Trust
Avijit Lahiri, MRCP FACC study director
Wellington Hospital
Daniel Darko, MRCP principal investigator
Central Middlesex Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 2 Diabetes and Coronary Artery Disease, run by British Cardiac Research Trust at 5 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shreenidhi M Venuraju, MRCP (+442074835062, shreenidhimv@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Greater than 20% increase in plaque volume (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02109835, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2015.