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

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ClinicalTrials.gov Identifier: NCT03132129
Recruitment Status : Recruiting
First Posted : April 27, 2017
Last Update Posted : June 1, 2020
Sponsor:
Information provided by (Responsible Party):
University of Leicester

Brief 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: 150 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. Fifty 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.


Condition or disease Intervention/treatment
Diabetes Mellitus, Type 2 Diabetic Cardiomyopathies Diagnostic Test: Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopy Diagnostic Test: Transthoracic echocardiography Diagnostic Test: Computed tomography coronary artery calcium scoring Diagnostic Test: Cardiopulmonary exercise testing

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Prevalence and Determinants of Subclinical Cardiovascular Dysfunction in Adults With Type 2 Diabetes Mellitus
Actual Study Start Date : October 24, 2017
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Type 2 diabetics 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.

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.

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.

Diagnostic Test: Cardiopulmonary exercise testing
Physician supervised incremental symptom limited cardiopulmonary exercise tolerance test with ECG and haemodynamic monitoring.

Healthy controls 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.

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.

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.

Diagnostic Test: Cardiopulmonary exercise testing
Physician supervised incremental symptom limited cardiopulmonary exercise tolerance test with ECG and haemodynamic monitoring.




Primary Outcome Measures :
  1. Myocardial steatosis [ Time Frame: 3 years ]
    Myocardial steatosis as an independent predictor of LV global longitudinal strain


Secondary Outcome Measures :
  1. Multivariate and independent predictors of LV systolic and diastolic function in type 2 diabetes [ Time Frame: 3 years ]
    Multivariate and independent predictors of LV systolic and diastolic function in type 2 diabetes

  2. Sensitivity of CMR versus echocardiography and BNP for detecting subclinical cardiovascular dysfunction in type 2 diabetes [ Time Frame: 3 years ]
    Sensitivity of CMR versus echocardiography and BNP for detecting subclinical cardiovascular dysfunction in type 2 diabetes

  3. Independent association of CMR measures with aerobic exercise capacity in type 2 diabetes [ Time Frame: 3 years ]
    Independent association of CMR measures (LV systolic and diastolic strain and strain rates) with aerobic exercise capacity (peak VO2) in type 2 diabetes

  4. Differences in LV remodelling (indexed LV mass) between cases and controls [ Time Frame: 3 years ]
    Differences in LV remodelling (indexed LV mass) between cases and controls

  5. Independent clinical and imaging predictors of major adverse cardiovascular and, in particular, heart failure events in the patients with type 2 diabetes [ Time Frame: 5 years ]
    Independent clinical and imaging predictors of major adverse cardiovascular and, in particular, heart failure events in the patients with type 2 diabetes

  6. Differences in cardiac MRI and echo-derived systolic and diastolic strain and strain rates between cases and controls. [ Time Frame: 3 years ]
    Differences in cardiac MRI and echo-derived systolic and diastolic strain and strain rates between cases and controls.

  7. Differences in coronary atheroma burden (CT coronary artery calcium score) between cases and controls [ Time Frame: 3 years ]
    Differences in coronary atheroma burden (CT coronary artery calcium score) between cases and controls

  8. Differences in aerobic exercise capacity (peak V02) between cases and controls [ Time Frame: 3 years ]
    Differences in aerobic exercise capacity (peak V02) between cases and controls

  9. Differences in myocardial perfusion reserve between cases and controls [ Time Frame: 3 years ]
    Differences in myocardial perfusion reserve between cases and controls

  10. Differences in heart rate variability between cases and controls [ Time Frame: 3 years ]
    Differences in heart rate variability between cases and controls


Biospecimen Retention:   Samples With DNA
Quantitative buffy coat and plasma samples will be stored for future potential biomarker and genotyping studies.


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Ages Eligible for Study:   50 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Cases will be adults with stable type 2 diabetes and no past medical history of known cardiovascular disease.
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03132129


Contacts
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Contact: Gerry P McCann, MD 01162583402 gpm12@le.ac.uk
Contact: Gaurav S Gulsin, MBChB(Hons) 01162583244 gg149@leicester.ac.uk

Locations
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United Kingdom
University of Leicester Recruiting
Leicester, United Kingdom
Contact: Gaurav S Gulsin, MRCP(UK)         
Sponsors and Collaborators
University of Leicester
Investigators
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Principal Investigator: Gerry P McCann, MD University of Leicester
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Responsible Party: University of Leicester
ClinicalTrials.gov Identifier: NCT03132129    
Other Study ID Numbers: 0580
First Posted: April 27, 2017    Key Record Dates
Last Update Posted: June 1, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Leicester:
Type 2 diabetes
Diabetic cardiomyopathy
Cardiovascular magnetic resonance
Additional relevant MeSH terms:
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Cardiomyopathies
Diabetic Cardiomyopathies
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Heart Diseases
Cardiovascular Diseases
Diabetes Complications
Calcium
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs