Manganese-enhanced Magnetic Resonance Imaging (MEMRI) in Heart Failure With Preserved Ejection Fraction

NCT06652763 | Recruiting

• 1 other identifier: 0883
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Heart failure with preserved ejection fraction (HFpEF) is a condition in which the heart cannot fill with blood effectively. As a result, people with HFpEF suffer fatigue, breathlessness, and develop swollen limbs. The condition often requires multiple admissions to hospital and is associated with a marked loss of lifespan. Despite being so common, very little is known about why people develop HFpEF and there are hardly any known treatments. Type 2 diabetes (T2D) is a major risk factor for HFpEF, and people with both HFpEF and diabetes are at a heightened risk of hospitalisation and premature death. It is unclear why the combination of diabetes and HFpEF is particularly harmful. This may be related to the hearts of people with type 2 diabetes being unable to take up the mineral calcium properly, as well as due to their hearts being less energy efficient. Both of these are vital to heart muscle pumping and filling, but until recently it has not been possible to assess these in humans. New advances in heart MRI scans, with dedicated scanner techniques and dyes (manganese contrast), now allow extremely detailed pictures of heart structure, function, calcium uptake and energy efficiency, all during the same scan. The investigators will enlist 40 volunteers with HFpEF (20 with T2D and 20 without T2D), and up to 20 healthy volunteers, to undergo a heart MRI scan with manganese contrast to assess calcium uptake and energy efficiency. This will allow the comparison of people with HFpEF with and without T2D, to see how their hearts are different to healthy volunteers.

Conditions

Type 2 Diabetes; Heart Failure With Preserved Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Ki

  Manganese influx constant as measured by MEMRI scan

  Baseline

Secondary Outcomes (14)

• T1 values

  Baseline

• Myocardial PCr/ATP ratio

  Baseline

• Left ventricular ejection fraction

  Baseline

• LV global longitudinal strain

  Baseline

• LV global circumferential strain

  Baseline

Study Arms (3)

HFpEF with T2D

Participants with heart failure with preserved ejection fraction and type 2 diabetes

Other: Minnesota Living with Heart Failure Questionnaire; Diagnostic Test: Echocardiogram; Diagnostic Test: Six-minute walk test; Diagnostic Test: Manganese-enhanced MRI and 31-P magnetic resonance spectroscopy; Diagnostic Test: Cardiovascular magnetic resonance scan; Diagnostic Test: Blood tests

HFpEF without T2D

Participants with heart failure with preserved ejection fraction but without type 2 diabetes

Other: Minnesota Living with Heart Failure Questionnaire; Diagnostic Test: Echocardiogram; Diagnostic Test: Six-minute walk test; Diagnostic Test: Manganese-enhanced MRI and 31-P magnetic resonance spectroscopy; Diagnostic Test: Cardiovascular magnetic resonance scan; Diagnostic Test: Blood tests

Controls

Healthy volunteers without heart failure or type 2 diabetes

Other: Minnesota Living with Heart Failure Questionnaire; Diagnostic Test: Echocardiogram; Diagnostic Test: Six-minute walk test; Diagnostic Test: Manganese-enhanced MRI and 31-P magnetic resonance spectroscopy; Diagnostic Test: Cardiovascular magnetic resonance scan; Diagnostic Test: Blood tests

Interventions

Minnesota Living with Heart Failure Questionnaire OTHER

Self-administered, validated questionnaire to assess symptoms of heart failure

Controls; HFpEF with T2D; HFpEF without T2D

Cardiovascular magnetic resonance scan DIAGNOSTIC_TEST

Scan including adenosine stress perfusion

Controls; HFpEF with T2D; HFpEF without T2D

Blood tests DIAGNOSTIC_TEST

Full blood count, Urea and electrolytes, Liver function tests, Glucose and HbA1c, Insulin and C-peptide, NTproBNP, High sensitive troponin I, storage of plasma for future analyses

Controls; HFpEF with T2D; HFpEF without T2D

Echocardiogram DIAGNOSTIC_TEST

Resting transthoracic echocardiogram to exclude valvular pathology and the assess indices of systolic and diastolic function and speckle tracking for strain

Controls; HFpEF with T2D; HFpEF without T2D

Six-minute walk test DIAGNOSTIC_TEST

Standardised, objective assessment of exercise capacity

Controls; HFpEF with T2D; HFpEF without T2D

Manganese-enhanced MRI and 31-P magnetic resonance spectroscopy DIAGNOSTIC_TEST

Using a 3-Tesla scanner, 31P magnetic resonance spectroscopy will be performed to obtain information regarding cardiac energetics. An intravenous infusion of manganese dipyridoxyl diphosphate (mangafodipir, MnDPDP) will be commenced at a rate of 1mL/min using a dose of 5µmol/kg (0.1mL/kg).

Controls; HFpEF with T2D; HFpEF without T2D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Primary and secondary care patients

You may qualify if:

• Capacity to provide informed consent
• Symptoms (e.g. breathlessness, orthopnoea, ankle swelling, fatigue), signs (e.g. elevated jugular venous pressure, peripheral oedema, third heart sound) or established diagnosis of HF with LV ejection fraction ≥ 50%, or
• Meets HFpEF diagnostic criteria in accordance with the HFA-PEFF diagnostic algorithm form the Heart Failure Association of the European Society of Cardiology, in which a score ≥5 points confirms diagnosis of HFpEF

You may not qualify if:

• Known diagnosis of Type 1 Diabetes
• Pregnancy or breast-feeding or females of child bearing age without a negative pregnancy test
• Receiving an investigational drug or device within 30 days prior to participating in the study
• Decompensated heart failure or pulmonary oedema
• History of prolonged corrected QT interval or torsades de pointes
• Second- or third-degree atrioventricular block
• Abnormal liver function tests (\> 3x upper limit of normal) or history of liver disease
• Baseline eGFR \< 30mL/min/1.73m2
• Any contraindications to MRI including implanted devices/pacemakers
• Severe native valve disease, restrictive cardiomyopathy, constrictive pericarditis or hypertrophic cardiomyopathy, myocarditis or takotsubo cardiomyopathy.
• Recent myocardial infarction within the previous 3 months
• Known diagnosis of pheochromocytoma

Sponsors & Collaborators

• University of Leicester: lead

Study Sites (1)

University of Leicester

Leicester, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Plasma will be stored for future analyses including established biomarkers and discovery studies such as proteomic, lipidomic, metabolomic and genomic analyses and other new methodologies that may be developed

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Echocardiography; Walk Test; Hematologic Tests

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Exercise Test; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Gerry P McCann, MD

  University of Leicester

  PRINCIPAL INVESTIGATOR

• Abhishek Dattani, MBBS

  University of Leicester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gerry P McCann, MD

CONTACT

+44 (0)116 258 3038; gpm12@leicester.ac.uk

Abhishek Dattani, MBBS

CONTACT

ad530@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: November 27, 2023
• First Posted: October 22, 2024
• Study Start: October 10, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): February 1, 2036
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

GB (1)