Heart Failure With Preserved Ejection FractionNCT06353750
Intracellular Magnesium and Heart Failure
An observational study of Heart Failure With Preserved Ejection Fraction and Hypomagnesemia, run by University of Oxford at 1 site in United Kingdom.
Trial summary
Low magnesium levels are surprisingly common in those with a heart condition known as HFpEF, where the heart pumps well but is too rigid to fill properly with blood. While routine blood tests can check magnesium levels, they don't tell us how much magnesium is actually inside the heart and muscle cells, where it's… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction, Hypomagnesemia
- What is being tested?
- Magnesium supplement
- Type of treatment
- Injection or infusion
- How many people
- 85 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 Apr 2024to 25 Apr 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Study investigators will contact those people who have participated in other ethically approved studies conducted at the research centre and have consented for their contact details to be retained in order to be contacted to take part in other research. Patients attending outpatient heart failure clinics will be identified by their routine clinical care team. Patients attending for clinical cardiac imaging as part of their routine care who indicate on their consent form that they are happy to take part in research will be identified by their routine clinical team.
General Inclusion Criteria
- Participant is willing and able to give informed consent for participation in the study.
- Participant aged at least 18 years old.
6.2.2 Additional inclusion criteria for participants in the HFpEF arm
- Clinical diagnosis of HFpEF
- HFA-PEFF score ≥ 5
6.2.3 Additional inclusion criteria for participants in the healthy and matched control arm
- HFA-PEFF < 3
- No known diagnosis of heart failure
6.3 Exclusion criteria
- Participant is unwilling or unable to give informed consent
- Any impediment to communication which, in the opinion of the investigator, might prevent the investigator communicating effectively with the patient during the study which could cause a safety or reliability concern.
- Any other condition which, in the opinion of the investigator, might affect the safety of the participant or reduce the reliability of the study results
- Involvement in any other research project where the procedures would affect the outcomes of this study.
- Individuals with NYHA class IV symptoms
- Known ischaemic heart disease, ICD, or CRT in situ.
- Individuals on oral magnesium supplementation
- Insulin dependent diabetes
- Standard contraindications to magnetic resonance imaging (MRI), (Metal clips or metallic foreign body, prior injury to the eye involving fragments of metal, prior shrapnel injuries, any other metallic or electronic implants affected by the magnetic field, history of severe claustrophobia, history of chronic kidneys disease, egg, or soya allergy)
- Heart transplant recipient
- Cardiomyopathy from infiltrative or storage diseases, muscular dystrophies, or with reversible causes, hypertrophic cardiomyopathy
- Moderate or greater valvular heart disease
- Acute HF requiring iv diuretics, inotropes, vasodilators, or hospitalisation within 6 weeks of screening
- BMI>40kg/m2 (due to MRS sensitivity).
- Pregnancy (due to magnesium infusion).
- Chronic kidney disease stage 4/5 (due to contrast injection)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Oxford Centre for Magnetic Resonance (OCMR)
Oxford, OX3 9DU
Jennifer L Holland, BMBS, jennifer.holland@wolfson.ox.ac.uk
Oliver Rider, BM BCh, oliver.rider@cardiov.ox.ac.uk
About this study
Official title: Exploring Intramyocellular Magnesium Augmentation: Implications for Myocardial and Skeletal Muscle Metabolism in Individuals With Heart Failure With Preserved Ejection Fraction
Low magnesium levels are surprisingly common in those with a heart condition known as HFpEF, where the heart pumps well but is too rigid to fill properly with blood. While routine blood tests can check magnesium levels, they don't tell us how much magnesium is actually inside the heart and muscle cells, where it's vital for energy and overall function. Our research aims to get a clearer picture by looking directly at the magnesium inside these cells and understanding its role in the body's energy production and usage. We're also interested in how magnesium levels affect symptoms and the body's handling of sugar. We're using advanced medical imaging techniques, like heart magnetic resonance imaging (MRI) and other heart and muscle function tests, at rest and when the heart is working hard to help answer these questions. We'll compare the magnesium levels inside the cells before and after giving a supplement of magnesium to see if this can make a difference in how the heart and muscles work.
Read the detailed description
Hypomagnesaemia is prevalent among patients suffering from heart failure with preserved ejection fraction (HFpEF), and in those with predisposing risk factors such as obesity and diabetes. The intricate link between hypomagnesaemia and the pathophysiological processes of HFpEF remains to be fully elucidated. However, its notable prevalence suggests a significant role in the onset and advancement of the disease. Serum magnesium (S-Mg) is commonly used to evaluate Mg status, however, it does not accurately reflect true intracellular Mg concentrations ([Mg2+]i), where this essential ion exerts its beneficial effects. Thus, previous literature lacks a thorough evaluation of [Mg2+]i in HFpEF, and specifically the potential impact of Mg replete physiology.
The research hypothesis is that [Mg2+]i is related to myocardial and skeletal muscle (SM) energetics and performance in patients with HFpEF. The study aims to explore the role of [Mg2+]i at a functional and cellular level in cardiac and SM, symptomatology, and insulin sensitivity; comparing a HFpEF population with healthy and matched controls.
Using the chemical shift difference in the resonance frequencies of the α- and β- phosphate resonances in magnetic resonance spectroscopy (MRS), [Mg2+]i will be measured, comparing it to S-Mg. Blood samples for cardiac biomarkers, electrolytes, and markers of HFpEF risk factors (such as lipid profile, HbA1C and TSH) will be taken and a calf leg raise performed. Advanced imaging techniques at rest and stress including cardiac magnetic resonance imaging (CMR), MRS and echocardiography will be performed. MRS measurements include cellular energetics (Phosphocreatine [PCr]/ATP), rate of myocardial ATP delivery (CK flux and KfCK) and skeletal muscle energetics (PCr recovery Tau). At two time points post-Mg augmentation (immediate and delayed [7-15 days]), investigations will be repeated.
This study aspires to quantify [Mg2+]i in the HFpEF population compared with healthy and matched controls, juxtapose its levels with S-Mg, and examine its significance in the pathophysiology, functional and cellular performance, and symptom presentation of HFpEF. The study aims to recruit 45 individuals with HFpEF, 20 healthy controls and 20 age-and sex-matched individuals over a 2-year period.
- Being tested
- Magnesium supplement
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnesium supplementOther
Intravenous magnesium supplement (10mmol).
| Study group | Role | What they receive |
|---|---|---|
| Individuals with heart failure with preserved ejection fraction (HFpEF) | * Clinical diagnosis of HFpEF
* HFA-PEFF score ≥ 5 Receives: Other: Magnesium supplement | |
| Healthy controls | * HFA-PEFF < 3
* No known diagnosis of heart failure Receives: Other: Magnesium supplement | |
| Matched controls | * HFA-PEFF < 3
* No known diagnosis of heart failure
* Age and sex-matched individuals to the HFpEF cohort Receives: Other: Magnesium supplement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Myocardial/ skeletal muscle metabolism and energetics at rest and stress.
Measuring myocardial metabolism (PCr/ATP, CK flux and KfCK, PDH flux), and skeletal muscle metabolism (PCr recovery Tau) at rest and stress. Measurements at three time points (pre-Mg infusion, immediately post and delayed (7-15 days) after Mg infusion, comparing HFpEF population with healthy and matched controls.
Measured: 7-15 days
Secondary outcomes (5)
Serum versus intracellular magnesium concentration
Comparing serum magnesium with intracellular magnesium concentrations using MRS, at all time points (pre-Mg infusion, and post (immediately and 7-15 days after) Mg infusion).
Measured: 7-15 days
Cardiac function
Comparing systolic and diastolic function (echocardiography) at rest and exercise at the three time points (pre-Mg infusion, immediately post and delayed (7-15 days) after Mg infusion), and assessing if [Mg2+] has a stronger correlation with cardiac function than serum Mg2+.
Measured: 7-15 days
Skeletal muscle performance
Comparing Calf raise test at the three time points (pre-Mg infusion, immediately post and delayed (7-15 days) after Mg infusion), and assessing if [Mg2+] has a stronger correlation with test performance than serum Mg2+.
Measured: 7-15 days
Symptoms
To assess if Mg2+ infusion affects perceived exercise tolerance (NYHA class and symptom questionnaire) at 2 time points (pre-Mg infusion, and 7-15 days post-Mg infusion).
Measured: 7-15 days
Insulin sensitivity
To assess if Mg2+ infusion affects a HOMA-IR score (based on fasted serum glucose and insulin levels).
To assess if Mg2+ infusion affects a HOMA-IR score (based on fasted serum glucose and insulin levels).
To assess if Mg2+ infusion affects a HOMA-IR score (based on fasted serum glucose and insulin levels).
To assess if Mg2+ infusion affects a HOMA-IR score (based on fasted serum glucose and insulin levels), comparing 2 time points (pre-Mg infusion, and 7-15 days post-Mg infusion).
Measured: 7-15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2024
- Study start15 Apr 2024 (estimated)
- Primary completion28 Feb 2026 (estimated)
- Study completion25 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation, Oxford University Hospitals NHS Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06353750
- Sponsor's protocol ID
- 331039
- Status last verified
- Mar 2024
- First submitted
- 2 Apr 2024
- Last updated
- 9 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring Intramyocellular Magnesium Augmentation: Implications for Myocardial and Skeletal Muscle Metabolism in Individuals With Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT06353750
- Acronym / sponsor ID
- 331039
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 85 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- British Heart Foundation, Oxford University Hospitals NHS Trust
- Study start
- 15 Apr 2024 (estimated)
- Primary completion
- 28 Feb 2026 (estimated)
- Study completion
- 25 Apr 2026 (estimated)
- First posted
- 9 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Low magnesium levels are surprisingly common in those with a heart condition known as HFpEF, where the heart pumps well but is too rigid to fill properly with blood. While routine blood tests can check magnesium levels, they don't tell us how much magnesium is actually inside the heart and muscle cells, where it's vital for energy and overall function. Our research aims to get a clearer picture by looking directly at the magnesium inside these cells and understanding its role in the body's energy production and usage. We're also interested in how magnesium levels affect symptoms and the body's handling of sugar. We're using advanced medical imaging techniques, like heart magnetic resonance imaging (MRI) and other heart and muscle function tests, at rest and when the heart is working hard to help answer these questions. We'll compare the magnesium levels inside the cells before and after giving a supplement of magnesium to see if this can make a difference in how the heart and muscles work.
Detailed description
Hypomagnesaemia is prevalent among patients suffering from heart failure with preserved ejection fraction (HFpEF), and in those with predisposing risk factors such as obesity and diabetes. The intricate link between hypomagnesaemia and the pathophysiological processes of HFpEF remains to be fully elucidated. However, its notable prevalence suggests a significant role in the onset and advancement of the disease. Serum magnesium (S-Mg) is commonly used to evaluate Mg status, however, it does not accurately reflect true intracellular Mg concentrations ([Mg2+]i), where this essential ion exerts its beneficial effects. Thus, previous literature lacks a thorough evaluation of [Mg2+]i in HFpEF, and specifically the potential impact of Mg replete physiology.
The research hypothesis is that [Mg2+]i is related to myocardial and skeletal muscle (SM) energetics and performance in patients with HFpEF. The study aims to explore the role of [Mg2+]i at a functional and cellular level in cardiac and SM, symptomatology, and insulin sensitivity; comparing a HFpEF population with healthy and matched controls.
Using the chemical shift difference in the resonance frequencies of the α- and β- phosphate resonances in magnetic resonance spectroscopy (MRS), [Mg2+]i will be measured, comparing it to S-Mg. Blood samples for cardiac biomarkers, electrolytes, and markers of HFpEF risk factors (such as lipid profile, HbA1C and TSH) will be taken and a calf leg raise performed. Advanced imaging techniques at rest and stress including cardiac magnetic resonance imaging (CMR), MRS and echocardiography will be performed. MRS measurements include cellular energetics (Phosphocreatine [PCr]/ATP), rate of myocardial ATP delivery (CK flux and KfCK) and skeletal muscle energetics (PCr recovery Tau). At two time points post-Mg augmentation (immediate and delayed [7-15 days]), investigations will be repeated.
This study aspires to quantify [Mg2+]i in the HFpEF population compared with healthy and matched controls, juxtapose its levels with S-Mg, and examine its significance in the pathophysiology, functional and cellular performance, and symptom presentation of HFpEF. The study aims to recruit 45 individuals with HFpEF, 20 healthy controls and 20 age-and sex-matched individuals over a 2-year period.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Individuals with heart failure with preserved ejection fraction (HFpEF) | – | Other: Magnesium supplement* Clinical diagnosis of HFpEF * HFA-PEFF score ≥ 5 |
| Healthy controls | – | Other: Magnesium supplement* HFA-PEFF < 3 * No known diagnosis of heart failure |
| Matched controls | – | Other: Magnesium supplement* HFA-PEFF < 3 * No known diagnosis of heart failure * Age and sex-matched individuals to the HFpEF cohort |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Study investigators will contact those people who have participated in other ethically approved studies conducted at the research centre and have consented for their contact details to be retained in order to be contacted to take part in other research. Patients attending outpatient heart failure clinics will be identified by their routine clinical care team. Patients attending for clinical cardiac imaging as part of their routine care who indicate on their consent form that they are happy to take part in research will be identified by their routine clinical team.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnesium supplementIntravenous magnesium supplement (10mmol). | Other | Healthy controls, Individuals with heart failure with preserved ejection fraction (HFpEF), Matched controls |
Primary outcome
Myocardial/ skeletal muscle metabolism and energetics at rest and stress.
Time frame: 7-15 days
Measuring myocardial metabolism (PCr/ATP, CK flux and KfCK, PDH flux), and skeletal muscle metabolism (PCr recovery Tau) at rest and stress. Measurements at three time points (pre-Mg infusion, immediately post and delayed (7-15 days) after Mg infusion, comparing HFpEF population with healthy and matched controls.
5 secondary outcomes
Serum versus intracellular magnesium concentration
Time frame: 7-15 days
Cardiac function
Time frame: 7-15 days
Skeletal muscle performance
Time frame: 7-15 days
Symptoms
Time frame: 7-15 days
Insulin sensitivity
Time frame: 7-15 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure With Preserved Ejection Fraction and Hypomagnesemia, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jennifer L Holland, BMBS (01865 221172, jennifer.holland@wolfson.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Myocardial/ skeletal muscle metabolism and energetics at rest and stress. (time frame: 7-15 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2024.