Prevalence and Determinants of Subclinical Cardiovascular Dysfunction in Adults With Type 2 Diabetes Mellitus

NCT ID: NCT03132129

Last Updated: 2024-01-05

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

RECRUITING

Total Enrollment

593 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-10-24

Study Completion Date

2029-10-31

Brief Summary

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Background: Heart failure is a major cause of morbidity and mortality in diabetes mellitus, but its pathophysiology is poorly understood.

Aim: To determine the prevalence and determinants of subclinical cardiovascular dysfunction in adults with type 2 diabetes (T2D).

Plan: 518 asymptomatic adults (aged 18-75 years) with T2D will undergo comprehensive evaluation of cardiac structure and function using cardiac MRI (CMR) and spectroscopy, echocardiography, CT coronary calcium scoring, exercise tolerance testing and blood sampling. 75 controls will undergo the same evaluation.

Primary hypothesis: myocardial steatosis is an independent predictor of left ventricular global longitudinal strain. Secondary hypotheses: will assess whether CMR is more sensitive to detect early cardiac dysfunction than echocardiography and BNP, and whether cardiac dysfunction is related to peak oxygen consumption.

Expected value of results: This study will reveal the prevalence and determinants of cardiac dysfunction in T2D, and could provide targets for novel therapies.

Detailed Description

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Conditions

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Diabetes Mellitus, Type 2 Diabetic Cardiomyopathies

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Type 2 diabetics

Participants will be aged (≥18 and ≤75 years) with T2D and no prior history of cardiovascular disease.

Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy

Intervention Type DIAGNOSTIC_TEST

CMR scanning performed on a 3T MRI scanner. Standardised protocol incorporating cine functional assessment to determine LV mass, systolic function and left atrial volumes; global systolic strain and diastolic strain rates will be assessed by tagging and with tissue tracking analysis from cine images, adenosine rest and stress myocardial perfusion to assess reserve index and qualitative perfusion defects as previously described, aortic distensibility and pulse wave velocity to measure aortic stiffness, delayed contrast enhancement for assessment of LV fibrosis and evidence of previous myocardial infarction. Myocardial and liver triglyceride content will be assessed using the modified Hepafat® sequence or 1H MR spectroscopy at the inter ventricular septum. DIXON technique for the quantification of visceral adiposity and subcutaneous adipose tissue.

Transthoracic echocardiography

Intervention Type DIAGNOSTIC_TEST

Comprehensive transthoracic echocardiography, including: tissue Doppler indices of diastolic filling and speckle tracking for systolic and diastolic strain/strain rate, exclusion of valvular abnormalities, assessment of LV size and function.

Computed tomography coronary artery calcium scoring

Intervention Type DIAGNOSTIC_TEST

Computed Tomography coronary calcium scoring to assess the presence of subclinical atherosclerosis and allow an estimate of atheroma burden in addition to epicardial adipose tissue characterisation and systolic strain.

Cardiopulmonary exercise testing

Intervention Type DIAGNOSTIC_TEST

Physician supervised incremental symptom limited cardiopulmonary exercise tolerance test with ECG and haemodynamic monitoring.

Manganese-enhanced magnetic resonance imaging (MEMRI)

Intervention Type DIAGNOSTIC_TEST

A subset of the participants will have cardiac MRI scanning with manganese-based contrast agent, lasting approximately 45-50 minutes. After localisers, baseline functions and native T1 maps have been acquired, Mangafodipir (0.1mL/kg) will be administered intravenously at 1ml/min, with additional T1 maps acquired every 2.5 min after administration of the contrast agent for up to 30 minutes.

Ambulatory blood pressure monitoring

Intervention Type DIAGNOSTIC_TEST

A 24-hour blood pressure monitor will be worn at the end of the visit to the following day.

Accelerometer watch

Intervention Type DIAGNOSTIC_TEST

Watch worn to collect free living physical activity data for 7 days.

Blood tests

Intervention Type DIAGNOSTIC_TEST

Collection of blood samples from each participant to characterise the participant's health status and to develop a proteomic signature of early heart failure.

Healthy controls

Cases will be compared with age-, gender- and ethnicity-matched healthy controls.

Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy

Intervention Type DIAGNOSTIC_TEST

CMR scanning performed on a 3T MRI scanner. Standardised protocol incorporating cine functional assessment to determine LV mass, systolic function and left atrial volumes; global systolic strain and diastolic strain rates will be assessed by tagging and with tissue tracking analysis from cine images, adenosine rest and stress myocardial perfusion to assess reserve index and qualitative perfusion defects as previously described, aortic distensibility and pulse wave velocity to measure aortic stiffness, delayed contrast enhancement for assessment of LV fibrosis and evidence of previous myocardial infarction. Myocardial and liver triglyceride content will be assessed using the modified Hepafat® sequence or 1H MR spectroscopy at the inter ventricular septum. DIXON technique for the quantification of visceral adiposity and subcutaneous adipose tissue.

Transthoracic echocardiography

Intervention Type DIAGNOSTIC_TEST

Comprehensive transthoracic echocardiography, including: tissue Doppler indices of diastolic filling and speckle tracking for systolic and diastolic strain/strain rate, exclusion of valvular abnormalities, assessment of LV size and function.

Computed tomography coronary artery calcium scoring

Intervention Type DIAGNOSTIC_TEST

Computed Tomography coronary calcium scoring to assess the presence of subclinical atherosclerosis and allow an estimate of atheroma burden in addition to epicardial adipose tissue characterisation and systolic strain.

Cardiopulmonary exercise testing

Intervention Type DIAGNOSTIC_TEST

Physician supervised incremental symptom limited cardiopulmonary exercise tolerance test with ECG and haemodynamic monitoring.

Manganese-enhanced magnetic resonance imaging (MEMRI)

Intervention Type DIAGNOSTIC_TEST

A subset of the participants will have cardiac MRI scanning with manganese-based contrast agent, lasting approximately 45-50 minutes. After localisers, baseline functions and native T1 maps have been acquired, Mangafodipir (0.1mL/kg) will be administered intravenously at 1ml/min, with additional T1 maps acquired every 2.5 min after administration of the contrast agent for up to 30 minutes.

Ambulatory blood pressure monitoring

Intervention Type DIAGNOSTIC_TEST

A 24-hour blood pressure monitor will be worn at the end of the visit to the following day.

Accelerometer watch

Intervention Type DIAGNOSTIC_TEST

Watch worn to collect free living physical activity data for 7 days.

Blood tests

Intervention Type DIAGNOSTIC_TEST

Collection of blood samples from each participant to characterise the participant's health status and to develop a proteomic signature of early heart failure.

Interventions

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Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy

CMR scanning performed on a 3T MRI scanner. Standardised protocol incorporating cine functional assessment to determine LV mass, systolic function and left atrial volumes; global systolic strain and diastolic strain rates will be assessed by tagging and with tissue tracking analysis from cine images, adenosine rest and stress myocardial perfusion to assess reserve index and qualitative perfusion defects as previously described, aortic distensibility and pulse wave velocity to measure aortic stiffness, delayed contrast enhancement for assessment of LV fibrosis and evidence of previous myocardial infarction. Myocardial and liver triglyceride content will be assessed using the modified Hepafat® sequence or 1H MR spectroscopy at the inter ventricular septum. DIXON technique for the quantification of visceral adiposity and subcutaneous adipose tissue.

Intervention Type DIAGNOSTIC_TEST

Transthoracic echocardiography

Comprehensive transthoracic echocardiography, including: tissue Doppler indices of diastolic filling and speckle tracking for systolic and diastolic strain/strain rate, exclusion of valvular abnormalities, assessment of LV size and function.

Intervention Type DIAGNOSTIC_TEST

Computed tomography coronary artery calcium scoring

Computed Tomography coronary calcium scoring to assess the presence of subclinical atherosclerosis and allow an estimate of atheroma burden in addition to epicardial adipose tissue characterisation and systolic strain.

Intervention Type DIAGNOSTIC_TEST

Cardiopulmonary exercise testing

Physician supervised incremental symptom limited cardiopulmonary exercise tolerance test with ECG and haemodynamic monitoring.

Intervention Type DIAGNOSTIC_TEST

Manganese-enhanced magnetic resonance imaging (MEMRI)

A subset of the participants will have cardiac MRI scanning with manganese-based contrast agent, lasting approximately 45-50 minutes. After localisers, baseline functions and native T1 maps have been acquired, Mangafodipir (0.1mL/kg) will be administered intravenously at 1ml/min, with additional T1 maps acquired every 2.5 min after administration of the contrast agent for up to 30 minutes.

Intervention Type DIAGNOSTIC_TEST

Ambulatory blood pressure monitoring

A 24-hour blood pressure monitor will be worn at the end of the visit to the following day.

Intervention Type DIAGNOSTIC_TEST

Accelerometer watch

Watch worn to collect free living physical activity data for 7 days.

Intervention Type DIAGNOSTIC_TEST

Blood tests

Collection of blood samples from each participant to characterise the participant's health status and to develop a proteomic signature of early heart failure.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Participant is willing and able to give informed consent for participation in the study.
* Male or Female, aged ≥18 and ≤75 years.
* Diagnosed with Stable type 2 diabetes (determined by: i) formal diagnosis in GP case records, ii) a record of diagnostic oral glucose tolerance test OR glycated haemoglobin level ≥6.5%).

Exclusion Criteria

* Angina pectoris or limiting dyspnoea (\>NYHA II),
* Major atherosclerotic disease: Symptomatic CAD, history of myocardial infarction, previous revascularisation, stroke/transient ischaemic attack or symptomatic peripheral vascular disease.
* Atrial fibrillation or flutter.
* Moderate or severe valvular heart disease.
* History of heart failure or cardiomyopathy.
* Type 1 diabetes mellitus (T1DM).
* Low fasting C-peptide levels suggestive of adult-onset T1DM.
* Stage III-V renal disease (estimated glomerular filtration rate ≤30ml/min/1.73m2).
* Absolute contraindications to CMR.

Importantly, patients with subclinical CAD, and other common comorbidities such as obesity and hypertension, will not be excluded from this study. This will enable us to evaluate the contribution of CAD to myocardial dysfunction in diabetes and ensures our study group is representative of the general population with diabetes. Similarly, as mild dyspnoea is extremely common and non-specific participants with mild dyspnoea will be included.
Minimum Eligible Age

50 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Leicester

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gerry P McCann, MD

Role: PRINCIPAL_INVESTIGATOR

University of Leicester

Locations

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University of Leicester

Leicester, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Gerry P McCann, MD

Role: CONTACT

01162583402

Gaurav S Gulsin, MBChB(Hons)

Role: CONTACT

01162583244

Facility Contacts

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Gaurav S Gulsin, MRCP(UK)

Role: primary

References

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Yeo JL, Gulsin GS, Brady EM, Dattani A, Bilak JM, Marsh AM, Sian M, Athithan L, Parke KS, Wormleighton J, Graham-Brown MPM, Singh A, Arnold JR, Lawson C, Davies MJ, Xue H, Kellman P, McCann GP. Association of ambulatory blood pressure with coronary microvascular and cardiac dysfunction in asymptomatic type 2 diabetes. Cardiovasc Diabetol. 2022 May 28;21(1):85. doi: 10.1186/s12933-022-01528-2.

Reference Type DERIVED
PMID: 35643571 (View on PubMed)

Other Identifiers

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0580

Identifier Type: -

Identifier Source: org_study_id

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