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

Diabetes Mellitus, Type 2 Clinical Trial

— PREDICT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03132129
• Other study ID #: 0580
• Status: Recruiting
• Start date: October 24, 2017
• Est. completion date: October 31, 2029

Study information

• Verified date: January 2024
• Source: University of Leicester
• Contact: Gerry P McCann, MD
• Phone: 01162583402
• Email: gpm12[@]le.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 593
• Est. completion date: October 31, 2029
• Est. primary completion date: October 31, 2029
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiomyopathies
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetic Cardiomyopathies

Intervention

Diagnostic Test:
• 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.
• 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.
• 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.
• Cardiopulmonary exercise testing
Physician supervised incremental symptom limited cardiopulmonary exercise tolerance test with ECG and haemodynamic monitoring.
• 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.
• Ambulatory blood pressure monitoring
A 24-hour blood pressure monitor will be worn at the end of the visit to the following day.
• Accelerometer watch
Watch worn to collect free living physical activity data for 7 days.
• 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.

Locations

Country	Name	City	State
United Kingdom	University of Leicester	Leicester

Sponsors (1)

Lead Sponsor	Collaborator
University of Leicester

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of early heart failure in type 2 diabetes	Proportion of participants with type 2 diabetes who have features of early heart failure	5 years
Secondary	Multivariate and independent predictors of LV systolic and diastolic function in type 2 diabetes	Multivariate and independent predictors of LV systolic and diastolic function in type 2 diabetes	3 years
Secondary	Sensitivity of CMR versus echocardiography and BNP for detecting subclinical cardiovascular dysfunction in type 2 diabetes	Sensitivity of CMR versus echocardiography and BNP for detecting subclinical cardiovascular dysfunction in type 2 diabetes	3 years
Secondary	Independent association of CMR measures with aerobic exercise capacity in type 2 diabetes	Independent association of CMR measures (LV systolic and diastolic strain and strain rates) with aerobic exercise capacity (peak VO2) in type 2 diabetes	3 years
Secondary	Differences in LV remodelling (indexed LV mass) between cases and controls	Differences in LV remodelling (indexed LV mass) between cases and controls	3 years
Secondary	Independent clinical and imaging predictors of major adverse cardiovascular and, in particular, heart failure events in the patients with type 2 diabetes	Independent clinical and imaging predictors of major adverse cardiovascular and, in particular, heart failure events in the patients with type 2 diabetes	5 years
Secondary	Differences in cardiac MRI and echo-derived systolic and diastolic strain and strain rates between cases and controls.	Differences in cardiac MRI and echo-derived systolic and diastolic strain and strain rates between cases and controls.	3 years
Secondary	Differences in coronary atheroma burden (CT coronary artery calcium score) between cases and controls	Differences in coronary atheroma burden (CT coronary artery calcium score) between cases and controls	3 years
Secondary	Differences in aerobic exercise capacity (peak V02) between cases and controls	Differences in aerobic exercise capacity (peak V02) between cases and controls	3 years
Secondary	Differences in myocardial perfusion reserve between cases and controls	Differences in myocardial perfusion reserve between cases and controls	3 years
Secondary	Differences in heart rate and blood pressure variability between cases and controls	Differences in heart rate and blood pressure variability between cases and controls	3 years
Secondary	Myocardial steatosis	Myocardial steatosis as an independent predictor of LV global longitudinal strain	3 years
Secondary	Myocardial calcium handling as assessed by manganese-enhanced magnetic resonance imaging (MEMRI)	Manganese influx constants calculated using Patlak modelling	5 years
Secondary	Proteomic signature	Proteomic analysis will be conducted to identify a proteomic signature of early heart failure in type 2 diabetes that will be externally validated	5 years
Secondary	Remission of type 2 diabetes	The phenotype of participants defined as in remission will be compared to active type 2 diabetes and healthy volunteers	5 years