NCT03132129

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: 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
593

participants targeted

Target at P75+ for all trials

Timeline
42mo left

Started Oct 2017

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress71%
Oct 2017Oct 2029

First Submitted

Initial submission to the registry

April 19, 2017

Completed
8 days until next milestone

First Posted

Study publicly available on registry

April 27, 2017

Completed
6 months until next milestone

Study Start

First participant enrolled

October 24, 2017

Completed
12 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2029

Last Updated

January 5, 2024

Status Verified

January 1, 2024

Enrollment Period

12 years

First QC Date

April 19, 2017

Last Update Submit

January 3, 2024

Conditions

Diabetes Mellitus, Type 2Diabetic Cardiomyopathies

Keywords

Type 2 diabetesDiabetic cardiomyopathyCardiovascular magnetic resonance

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (14)

  • Multivariate and independent predictors of LV systolic and diastolic function in type 2 diabetes

    3 years

  • Sensitivity of CMR versus echocardiography and BNP for detecting subclinical cardiovascular dysfunction in type 2 diabetes

    3 years

  • Independent association of CMR measures with aerobic exercise capacity in type 2 diabetes

    3 years

  • Differences in LV remodelling (indexed LV mass) between cases and controls

    3 years

  • Independent clinical and imaging predictors of major adverse cardiovascular and, in particular, heart failure events in the patients with type 2 diabetes

    5 years

  • +9 more secondary outcomes

Study Arms (2)

Type 2 diabetics

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

Diagnostic Test: Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopyDiagnostic Test: Transthoracic echocardiographyDiagnostic Test: Computed tomography coronary artery calcium scoringDiagnostic Test: Cardiopulmonary exercise testingDiagnostic Test: Manganese-enhanced magnetic resonance imaging (MEMRI)Diagnostic Test: Ambulatory blood pressure monitoringDiagnostic Test: Accelerometer watchDiagnostic Test: Blood tests

Healthy controls

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

Diagnostic Test: Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopyDiagnostic Test: Transthoracic echocardiographyDiagnostic Test: Computed tomography coronary artery calcium scoringDiagnostic Test: Cardiopulmonary exercise testingDiagnostic Test: Manganese-enhanced magnetic resonance imaging (MEMRI)Diagnostic Test: Ambulatory blood pressure monitoringDiagnostic Test: Accelerometer watchDiagnostic Test: Blood tests

Interventions

Cardiovascular magnetic resonance (CMR) imaging and magnetic resonance spectroscopyDIAGNOSTIC_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.

Healthy controlsType 2 diabetics
Transthoracic echocardiographyDIAGNOSTIC_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.

Healthy controlsType 2 diabetics
Computed tomography coronary artery calcium scoringDIAGNOSTIC_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.

Healthy controlsType 2 diabetics
Cardiopulmonary exercise testingDIAGNOSTIC_TEST

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

Healthy controlsType 2 diabetics
Manganese-enhanced magnetic resonance imaging (MEMRI)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.

Healthy controlsType 2 diabetics
Ambulatory blood pressure monitoringDIAGNOSTIC_TEST

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

Healthy controlsType 2 diabetics
Accelerometer watchDIAGNOSTIC_TEST

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

Healthy controlsType 2 diabetics
Blood testsDIAGNOSTIC_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 controlsType 2 diabetics

Eligibility Criteria

Age50 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Cases will be adults with stable type 2 diabetes and no past medical history of known cardiovascular disease.

You may qualify if:

  • 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%).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Leicester

Leicester, United Kingdom

RECRUITING

Related Publications (1)

  • 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.

    PMID: 35643571DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Quantitative buffy coat and plasma samples will be stored for future potential biomarker and genotyping studies.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Diabetic Cardiomyopathies

Interventions

Diagnostic ImagingPositron-Emission TomographyEchocardiographyExercise TestBlood Pressure Monitoring, AmbulatoryHematologic Tests

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesCardiomyopathiesHeart DiseasesCardiovascular DiseasesDiabetes Complications

Intervention Hierarchy (Ancestors)

Diagnostic Techniques and ProceduresDiagnosisTomography, Emission-ComputedImage Interpretation, Computer-AssistedImage EnhancementPhotographyRadionuclide ImagingTomographyDiagnostic Techniques, RadioisotopeCardiac Imaging TechniquesUltrasonographyHeart Function TestsDiagnostic Techniques, CardiovascularRespiratory Function TestsDiagnostic Techniques, Respiratory SystemErgometryInvestigative TechniquesBlood Pressure DeterminationMonitoring, AmbulatoryMonitoring, PhysiologicClinical Laboratory Techniques

Study Officials

  • Gerry P McCann, MD

    University of Leicester

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Gerry P McCann, MD

CONTACT

01162583402gpm12@le.ac.uk

Gaurav S Gulsin, MBChB(Hons)

CONTACT

01162583244gg149@leicester.ac.uk

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 19, 2017

First Posted

April 27, 2017

Study Start

October 24, 2017

Primary Completion (Estimated)

October 31, 2029

Study Completion (Estimated)

October 31, 2029

Last Updated

January 5, 2024

Record last verified: 2024-01

Data Sharing

IPD Sharing
Will not share

Locations

GB(1)