Aortic Valve StenosisOxFASTNCT05256758
Oxford - Fibrates in Aortic Stenosis
A study testing Fenofibrate Capsules and Placental Lactogen in people with Aortic Valve Stenosis, run by University of Oxford at 1 site in United Kingdom.
Trial summary
Aortic stenosis (AS) is characterised by left ventricular (LV) hypertrophy and altered myocardial substrate metabolism. Peroxisome proliferator-activated receptor (PPARα), a regulator of lipid metabolism is deactivated in pressure overload hypertrophy such as in AS and can lead to dysregulation of fatty acid… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Valve Stenosis
- What is being tested?
- Fenofibrate Capsules and Placental Lactogen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 29 May 2019to 31 Mar 2022
- Phase
- Interventional
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Asymptomatic moderate to severe AS (with at least two of the following: aortic valve area <1.5 cm2, peak pressure gradient >36 mmHg or mean pressure gradient >25 mmHg)
- Not planned aortic valve replacement or transcatheter aortic valve implantation (TAVI)
- Age >18
- No other significant valvular pathology
- No contraindication to magnetic resonance imaging.
Who cannot join
- Known coronary artery disease, history of angina, myocardial infarction or presence of regional wall motion abnormalities
- Other underlying cardiomyopathy
- Left ventricular ejection fraction<50%
- Uncontrolled hypertension
- Diabetes Mellitus
- Liver impairment
Show all 10Show fewer
- Pregnancy and lactation
- Body mass index >35 kg/m2
- Renal impairment (eGFR<30 ml/min)
- Intolerance to or concurrent use of fibrates or PPARα agonists.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Altering Myocardial Lipid Content on Cardiac Physiology in Patients With Aortic Stenosis
Aortic stenosis (AS) is characterised by left ventricular (LV) hypertrophy and altered myocardial substrate metabolism. Peroxisome proliferator-activated receptor (PPARα), a regulator of lipid metabolism is deactivated in pressure overload hypertrophy such as in AS and can lead to dysregulation of fatty acid oxidation, myocardial triglyceride accumulation (steatosis) and lipotoxicity. The investigators propose a proof-of-concept study to investigate the effect of altering myocardial triglyceride (MTG) using a PPARα agonist, fenofibrate on cardiac physiology in patients with asymptomatic moderate-severe AS. The primary endpoint is a change in MTG assessed by magnetic resonance spectroscopy at baseline and after 6 months of treatment. Exploratory endpoints are changes in cardiac physiology including myocardial deformation (strain) as assessed by cardiac magnetic resonance imaging. The investigators hypothesise that pharmacological reduction of MTG with a PPARα agonist will result in steatosis regression and changes in cardiac physiology.
Read the detailed description
This is a single-centre, proof-of-concept study to investigate the effect of altering MTG content using fenofibrate on cardiac physiology in patients with asymptomatic moderate-severe AS. All patients will participate in a randomised, double-blind, placebo- controlled design for 6 months. AS will be graded according to the British Society of Echocardiography's transthoracic echocardiography guidelines. Sixty two eligible patients will be recruited in total, of which forty nine patients will be randomised to receive 200 mg daily oral fenofibrate and thirteen patients will receive matching placebo for 6 months. All patients will undergo 1H-MRS to assess MTG, 31P-MRS to assess myocardial energetic (Phosphocreatine-to-ATP ratio - PCr/ATP), standard cardiac magnetic resonance imaging to assess LV strain, LV mass, late gadolinium enhancement (fibrosis), physiological exercise assessments to measure maximum oxygen consumption (VO2 max) and 6-minute walking distance. Bloods will be drawn for cholesterol, renal and liver function, glucose and free fatty acids. All tests will be done at baseline and after 6 months' treatment with fenofibrate/placebo.
- Conditions
- Aortic Valve Stenosis
- Being tested
- Fenofibrate Capsules, Placental Lactogen
- Medical subject headings
- Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fenofibrate CapsulesDrug
Also called Fenofibrate
49 patients randomised to receive fenofibrate for 6 months.
Placental LactogenDrug
13 patients randomised to receive placebo for 6 months.
| Study group | Role | What they receive |
|---|---|---|
| OxFAST Fibrate group | Experimental | 49 patients randomised to receive fenofibrate 200mg capsules. Receives: Drug: Fenofibrate Capsules |
| OxFAST placebo group | Placebo comparator | 13 patients randomised to receive placebo will act as controls. Receives: Drug: Placental Lactogen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in myocardial triglyceride (MTG) content as assessed by cardiac magnetic resonance (CMR) spectroscopy
All participants will undergo blood tests (full blood count, renal and liver function, lipid profile, free fatty acids and NT- proBNP), CMR cine imaging for assessment of cardiac volumes, function including strain (myocardial tagging), aortic valve imaging and late gadolinium enhancement will be undertaken.
MTG will be assessed using cardiac 1H-MRS (proton spectroscopy), which utilises the abundant hydrogen (1H) protons. For 1H-MRS, data are typically acquired at breath hold during diastole from a single voxel (14-16mL) localised in the myocardial septum and take 10-15 minutes to acquire. Myocardial lipid content is calculated as myocardial lipid/water ratio and expressed as percentage.
It is hypothesised that Fenofibrate, PPAR alpha agonist will shift the cardiac metabolism back to mainly using free fatty acids and hence the investigators may see a reduction in myocardial lipid content.
Measured: 6 months
Secondary outcomes (2)
Change in myocardial energetics (PCr/ATP ratio) as assessed by Phosphorous magnetic resonance spectroscopy
31P-MRS (Phosphorous Spectroscopy) allows the in vivo quantification of phosphorus (31P)-containing metabolites involved in energy metabolism, such as Phosphocreatine and ATP (Adenosine Triphosphate). PCr/ATP ratio is a reliable indicator of myocardial energetics. It is hypothesised that fenofibrate will increase fatty acid metabolism in the heart and subsequently improve the energetic status of the heart.
Measured: 6 months
Change in left ventricular function measured using CMR imaging
The investigators will assess the effect of altering cardiac metabolism using Fenofibrate and study its effect on cardiac physiology, mainly left ventricular function using CMR imaging. Strain assessment using myocardial tagging analysis will be used to detect subclinical dysfunction. The strain values are expressed as percentage.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2022
- Study start29 May 2019
- Primary completion31 Mar 2022 (estimated)
- Study completion31 Mar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aortic Valve StenosisStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised double-blind placebo controlled study
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation
- Responsible party
- Sponsor
- Investigators
- Mahmod, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05256758
- Sponsor's protocol ID
- OxFAST
- Acronym
- OxFAST
- Status last verified
- Jan 2022
- First submitted
- 20 Jan 2022
- Last updated
- 25 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Altering Myocardial Lipid Content on Cardiac Physiology in Patients With Aortic Stenosis
- ClinicalTrials.gov ID
- NCT05256758
- Acronym / sponsor ID
- OxFAST / OxFAST
- Conditions
- Aortic Valve Stenosis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 67 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- British Heart Foundation
- Study start
- 29 May 2019 (actual)
- Primary completion
- 31 Mar 2022 (estimated)
- Study completion
- 31 Mar 2022 (estimated)
- First posted
- 25 Feb 2022 (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.
Aortic stenosis (AS) is characterised by left ventricular (LV) hypertrophy and altered myocardial substrate metabolism. Peroxisome proliferator-activated receptor (PPARα), a regulator of lipid metabolism is deactivated in pressure overload hypertrophy such as in AS and can lead to dysregulation of fatty acid oxidation, myocardial triglyceride accumulation (steatosis) and lipotoxicity. The investigators propose a proof-of-concept study to investigate the effect of altering myocardial triglyceride (MTG) using a PPARα agonist, fenofibrate on cardiac physiology in patients with asymptomatic moderate-severe AS. The primary endpoint is a change in MTG assessed by magnetic resonance spectroscopy at baseline and after 6 months of treatment. Exploratory endpoints are changes in cardiac physiology including myocardial deformation (strain) as assessed by cardiac magnetic resonance imaging. The investigators hypothesise that pharmacological reduction of MTG with a PPARα agonist will result in steatosis regression and changes in cardiac physiology.
Detailed description
This is a single-centre, proof-of-concept study to investigate the effect of altering MTG content using fenofibrate on cardiac physiology in patients with asymptomatic moderate-severe AS. All patients will participate in a randomised, double-blind, placebo- controlled design for 6 months. AS will be graded according to the British Society of Echocardiography's transthoracic echocardiography guidelines. Sixty two eligible patients will be recruited in total, of which forty nine patients will be randomised to receive 200 mg daily oral fenofibrate and thirteen patients will receive matching placebo for 6 months. All patients will undergo 1H-MRS to assess MTG, 31P-MRS to assess myocardial energetic (Phosphocreatine-to-ATP ratio - PCr/ATP), standard cardiac magnetic resonance imaging to assess LV strain, LV mass, late gadolinium enhancement (fibrosis), physiological exercise assessments to measure maximum oxygen consumption (VO2 max) and 6-minute walking distance. Bloods will be drawn for cholesterol, renal and liver function, glucose and free fatty acids. All tests will be done at baseline and after 6 months' treatment with fenofibrate/placebo.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomised double-blind placebo controlled study
| Arm | Type | Receives |
|---|---|---|
| OxFAST Fibrate group | Experimental | Drug: Fenofibrate Capsules49 patients randomised to receive fenofibrate 200mg capsules. |
| OxFAST placebo group | Placebo comparator | Drug: Placental Lactogen13 patients randomised to receive placebo will act as controls. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Asymptomatic moderate to severe AS (with at least two of the following: aortic valve area <1.5 cm2, peak pressure gradient >36 mmHg or mean pressure gradient >25 mmHg)
- Not planned aortic valve replacement or transcatheter aortic valve implantation (TAVI)
- Age >18
- No other significant valvular pathology
- No contraindication to magnetic resonance imaging.
Key exclusion criteria (10 listed)
- Known coronary artery disease, history of angina, myocardial infarction or presence of regional wall motion abnormalities
- Other underlying cardiomyopathy
- Left ventricular ejection fraction<50%
- Uncontrolled hypertension
- Diabetes Mellitus
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 |
|---|---|---|
| Fenofibrate CapsulesAlso: Fenofibrate49 patients randomised to receive fenofibrate for 6 months. | Drug | OxFAST Fibrate group |
| Placental Lactogen13 patients randomised to receive placebo for 6 months. | Drug | OxFAST placebo group |
Primary outcome
Change in myocardial triglyceride (MTG) content as assessed by cardiac magnetic resonance (CMR) spectroscopy
Time frame: 6 months
All participants will undergo blood tests (full blood count, renal and liver function, lipid profile, free fatty acids and NT- proBNP), CMR cine imaging for assessment of cardiac volumes, function including strain (myocardial tagging), aortic valve imaging and late gadolinium enhancement will be undertaken. MTG will be assessed using cardiac 1H-MRS (proton spectroscopy), which utilises the abundant hydrogen (1H) protons. For 1H-MRS, data are typically acquired at breath hold during diastole from a single voxel (14-16mL) localised in the myocardial septum and take 10-15 minutes to acquire. Myocardial lipid content is calculated as myocardial lipid/water ratio and expressed as percentage. It is hypothesised that Fenofibrate, PPAR alpha agonist will shift the cardiac metabolism back to mainly using free fatty acids and hence the investigators may see a reduction in myocardial lipid content.
2 secondary outcomes
Change in myocardial energetics (PCr/ATP ratio) as assessed by Phosphorous magnetic resonance spectroscopy
Time frame: 6 months
Change in left ventricular function measured using CMR imaging
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2022.
- Individual participant dataSharing planned: Undecided
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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.
Mahmod principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fenofibrate Capsules and Placental Lactogen in people with Aortic Valve Stenosis, 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?
The sponsor lists 5 inclusion and 10 exclusion criteria. 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 25 Feb 2022. 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. Some participants in this study may receive a placebo. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in myocardial triglyceride (MTG) content as assessed by cardiac magnetic resonance (CMR) spectroscopy (time frame: 6 months). 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 25 Feb 2022.