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

NCT ID: NCT06652763

Last Updated: 2024-12-03

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

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-10-10

Study Completion Date

2036-02-29

Brief Summary

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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.

Detailed Description

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Conditions

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Heart Failure With Preserved Ejection Fraction Type 2 Diabetes

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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HFpEF with T2D

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

Minnesota Living with Heart Failure Questionnaire

Intervention Type OTHER

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

Echocardiogram

Intervention Type DIAGNOSTIC_TEST

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

Six-minute walk test

Intervention Type DIAGNOSTIC_TEST

Standardised, objective assessment of exercise capacity

Manganese-enhanced MRI and 31-P magnetic resonance spectroscopy

Intervention Type 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).

Cardiovascular magnetic resonance scan

Intervention Type DIAGNOSTIC_TEST

Scan including adenosine stress perfusion

Blood tests

Intervention Type 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

HFpEF without T2D

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

Minnesota Living with Heart Failure Questionnaire

Intervention Type OTHER

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

Echocardiogram

Intervention Type DIAGNOSTIC_TEST

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

Six-minute walk test

Intervention Type DIAGNOSTIC_TEST

Standardised, objective assessment of exercise capacity

Manganese-enhanced MRI and 31-P magnetic resonance spectroscopy

Intervention Type 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).

Cardiovascular magnetic resonance scan

Intervention Type DIAGNOSTIC_TEST

Scan including adenosine stress perfusion

Blood tests

Intervention Type 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

Healthy volunteers without heart failure or type 2 diabetes

Minnesota Living with Heart Failure Questionnaire

Intervention Type OTHER

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

Echocardiogram

Intervention Type DIAGNOSTIC_TEST

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

Six-minute walk test

Intervention Type DIAGNOSTIC_TEST

Standardised, objective assessment of exercise capacity

Manganese-enhanced MRI and 31-P magnetic resonance spectroscopy

Intervention Type 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).

Cardiovascular magnetic resonance scan

Intervention Type DIAGNOSTIC_TEST

Scan including adenosine stress perfusion

Blood tests

Intervention Type 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

Interventions

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Minnesota Living with Heart Failure Questionnaire

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

Intervention Type OTHER

Echocardiogram

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

Intervention Type DIAGNOSTIC_TEST

Six-minute walk test

Standardised, objective assessment of exercise capacity

Intervention Type DIAGNOSTIC_TEST

Manganese-enhanced MRI and 31-P magnetic resonance spectroscopy

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).

Intervention Type DIAGNOSTIC_TEST

Cardiovascular magnetic resonance scan

Scan including adenosine stress perfusion

Intervention Type DIAGNOSTIC_TEST

Blood tests

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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 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

Abhishek Dattani, MBBS

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

+44 (0)116 258 3038

Abhishek Dattani, MBBS

Role: CONTACT

Facility Contacts

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Gerry P McCann, MD

Role: primary

0116 2583038

Abhishek Dattani, MBBS

Role: backup

Other Identifiers

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0883

Identifier Type: -

Identifier Source: org_study_id