Condition category
Nutritional, Metabolic, Endocrine
Date applied
13/11/2015
Date assigned
26/11/2015
Last edited
26/11/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
A cardiovascular (CV) event refers to an event that causes damage to the heart muscle. This includes any interruption to the blood supply to the heart (such as a blockage of the coronary artery) . People with diabetes are at an high risk of a CV event and it is therefore very important to take steps to prevent them from occurring. This need is highlighted further by the failure of intensive changes to lifestyle and of most oral glucose (blood sugar) lowering treatments (except metformin and recently, Empagliflozin) to reduce CV events. On top of obvious signs of heart disease, a major problem in diabetes is the high number of people with silent but potentially lethal heart disease, i.e. silent ischaemia (inadequate blood supply to the heart but without symptoms), left ventricular hypertrophy (enlargement of the left ventricle of the heart – the part of the heart that pumps blood around the body), left ventricular systolic dysfunction (where the left ventricle does not contract properly), left ventricular diastolic dysfunction (where the left ventricle does not relax normally to let the heart fill with blood before it is pumped around the body) and left atrial enlargement (enlargement of a part of the heart containing blood from the lungs). The purpose of this study is to see how many people with asymptomatic type 2 diabetes (that is, without any symptoms) have multiple silent cardiac abnormalities and whether are there biomarkers (something that can be measured, for example, in the blood) which can identify these silent abnormalities early.

Who can participate?
Patients with type 2 diabetes aged 40 to 85 with no previous known cardiovascular symptoms or events, well controlled blood pressure, well controlled diabetes, no kidney problems and no significant heart disease.

What does the study involve?
After fasting beforehand, blood tests are taken from each participant. They then have a ultrasound scan of their heart (Echo) followed by Dobutamine stress Echo (DSE), a test to assess the hearts function and structures. Should the DSE be contraindicated (that is, if there is any reason why it should not be performed on a patient) or if no conclusions can be drawn from the results, participants have either Myocardial Perfusion Scan (MPS), a procedure where tissues are examined with the help of a tiny amount of radioactive substance or Computed Tomography Coronary Angiogram (CTCA), a technique for looking at the coronary arteries. 24 hour blood pressure data is also collected. This data is then used to identify participants with silent heart disease and how accurately biomarkers such as High-sensitive troponin T and N-terminal pro-B type natriuretic peptide can detect this disease.

What are the possible benefits and risks of participating?
If data from this study suggests that there are specific tests and markers that may predict heart disease in type 2 diabetes patients who have no symptoms, they can then be given medication to prevent them from developing life threatening events arising from the heart, if this is appropriate. Possible major complications with DSE are heart attack, abnormal heart rhythm and allergic reactions, but these are rare. Minor complications with DSE include palpitations, chest pain, shortness of breath, nausea, vomiting, dizziness and flushing. Participants will receive betablockers to slow down their heart rate for CTCA. The lifetime risk of developing cancer due to this scan would be approximately 1 in 1400 people but this is much smaller than the lifetime risk of developing cancer in the UK, which is 4 in 10 people. On rare occasions, for example if participants have faster heart rate despite betablockers, a slightly larger amount of radiation may be used. There is also a small risk of developing a reaction to the contrast agent. Participants will receive Dipyridamole if necessary for MPS. The lifetime risk of developing cancer due to MPS is approximately 1 in 1700 people. This is much smaller than the lifetime risk of developing cancer in the UK, which is 4 in 10 people. Dipyridamole medicine is safe and tolerable. Some may experience minor side effects such as dizziness, headache, nausea and chest discomfort. These symptoms usually last only a few minutes.

Where is the study run from?
Ninewells Hospital & Medical School, Dundee (UK)

When is the study starting and how long is it expected to run for?
August 2015 to August 2017.

Who is funding the study?
Chief Scientist Office, Scotland (UK)

Who is the main contact?
Dr. Vun Heng Chong
v.h.chong@dundee.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Dr Vun Heng Chong

ORCID ID

http://orcid.org/0000-0002-7196-905X

Contact details

University of Dundee
Division of Cardiovascular & Diabetes Medicine
Mailbox 2
Level 7
Ninewells Hospital & Medical School
Dundee
DD1 9SY
United Kingdom
+44(0)138 238 3346
v.h.chong@dundee.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

2013DM14

Study information

Scientific title

B-type natriuretic peptide (BNP) for personalised primary prevention in diabetes: a cross-sectional observational study

Acronym

4P

Study hypothesis

The primary prevention of cardiovascular (CV) events needs to improve because diabetic patients have such a high CV event rate. This need is underscored further by the failure of intensive lifestyle intervention and of most oral glucose lowering agents (except metformin and recently, empagliflozin) to reduce CV events. On top of overt heart disease, a major problem in diabetes is the high incidence of silent but potentially lethal heart disease, i.e. silent ischaemia, left ventricular hypertrophy, left ventricular systolic dysfunction, left ventricular diastolic dysfunction and left atrial enlargement. The purpose of this study is to assess how many people with asymptomatic type 2 diabetes have multiple silent cardiac abnormalities and is there a biomarker(s) which can early identify these silent abnormalities.

Ethics approval

East of Scotland Research Ethics Service, 07/04/2015, ref: 15/ES/0042

Study design

Single-centre cross-sectional observational study

Primary study design

Observational

Secondary study design

Cross sectional study

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

Not available in web format, please use the contact details below to request a participant information sheet

Condition

Type 2 diabetes mellitus

Intervention

All patients will undergo a blood test followed by a detailed Echo to assess for left ventricular systolic and diastolic function, left atrial size and left ventricular size. Dobutamine stress Echo (DSE) will be performed to assess for evidence of inducible myocardial ischaemia. In patients whose DSE is inconclusive or DSE is contraindicated, they would then undergo myocardial perfusion scan or CT coronary angiogram. 24 hour blood pressure date will be collected too.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Prevalence of silent heart disease in asymptomatic patients with well-controlled diabetes, assessed with Echo (for left ventricular systolic function, left ventricular diastolic function, left ventricular size, left atrial size) and Dobutamine stress Echo (for inducible ischaemia). This is assessed during participant’s single visit to study centre.

Secondary outcome measures

Accuracy of BNP ± hsTNT as a screening tool for the aforementioned silent heart disease, by assessing correlation of these biomarkers separately and in combination with the silent heart disease. This is further compared with other potential biomarkers in identification of silent heart disease, e.g. uric acid, hs-CRP, neutrophil to lymphocyte count. This is assessed at the end of study, i.e. 18-24 months after commencement of study.

Overall trial start date

05/08/2015

Overall trial end date

01/08/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 40-85 years
2. Type 2 diabetes with no previous known cardiovascular symptoms or events
3. Clinic blood pressure (BP) or average 24hour BP ≤140/80mmHg
4. HbA1c value <64 mmol/mol

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

246

Participant exclusion criteria

1. Clinic BP and average 24hour BP ≥140/80mmHg
2. Renal impairment (eGFR <60)
3. Atrial fibrillation
4. Significant (defined as more than mild) valvular heart disease either on auscultation or echocardiography
5. Pregnant type 2 diabetics
6. Unable to consent

Recruitment start date

18/11/2015

Recruitment end date

01/08/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Ninewells Hospital & Medical School
University of Dundee Division of Cardiovascular & Diabetes Medicine Ninewells Hospital & Medical School
Dundee
DD1 9SY
United Kingdom

Sponsor information

Organisation

University of Dundee & NHS Tayside

Sponsor details

Tayside Medical Sciences Manager
Ninewells Hospital & Medical School
TASC Research & Development Office
Residency Block
Level 3
George Pirrie Way
Dundee
DD1 9SY
United Kingdom
+44(0) 138 238 3890
CForde@dundee.ac.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Chief Scientist Office

Alternative name(s)

CSO

Funding Body Type

government organisation

Funding Body Subtype

government non-federal

Location

United Kingdom

Results and Publications

Publication and dissemination plan

We are intending to publish our study data: Prevalence of silent heart disease in asymptomatic patients with well-controlled diabetes and correlation of BNP ± hsTNT with these silent heart disease.
Intention to publish date is tentatively around August 2017.

Intention to publish date

31/08/2017

Participant level data

Stored in repository

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes