Cardiomyopathy, HypertrophicPhase 1NCT03251287
Nitrite in Hypertrophic Cardiomyopathy (HCM) Study
A Phase 1 study testing Sodium Nitrate, Phosphorous Magnetic Resonance Spectroscopy and Exercise Stress Transthoracic Echocardiogram in people with Cardiomyopathy, Hypertrophic, run by University of East Anglia at 1 site in United Kingdom.
Trial summary
Inorganic nitrate, which is found at high levels in green leafy vegetables, is reduced to nitrite by bacteria in the mouth, swallowed, and absorbed in the stomach into the blood. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cardiomyopathy, Hypertrophic
- What is being tested?
- Sodium Nitrate, Phosphorous Magnetic Resonance Spectroscopy and Exercise Stress Transthoracic Echocardiogram
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2017to Jan 2019
- Phase
- Phase 1
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, aged between 18 and 80 years.
- Able to provide informed consent.
- Able to understand basic instructions in English.
- A diagnosis of hypertrophic cardiomyopathy based on conventional transthoracic echocardiogram guidelines: left ventricular wall thickness >1.5cm in the absence of sufficient alternative cause.
- Exercise limited by symptoms on exertion (NYHA Class II symptoms or greater).
- PeakVO2 <80% on baseline CPEX.
- The absence of resting LV outflow tract obstruction (peak gradient <30 mm Hg) on TTE.
Who cannot join
- Significant medical, surgical or psychiatric disease that in the opinion of the patient's attending physician would affect subject safety or influence the study outcome.
- Contraindications for undergoing MRI.
- Hypotension with a systolic blood pressure <90mmHg.
- Severe anaemia with a plasma haemoglobin level <8.0g/dL.
- Known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD deficiency measured at screening in males of African, Asian or Mediterranean decent.
- Female subjects of childbearing potential.
- Haemodynamically significant valve disease.
- Predisposed to acute on chronic limb ischemia evident from a history of claudication or known peripheral arterial disease.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Norfolk and Norwich University Hospitals NHS Foundation Trust
Norwich, Norfolk, NR4 7UY
Brodie L Loudon, MBBS, 44(0) 1603 591 216, b.loudon@uea.ac.uk
Sunil V Nair, MD
About this study
Official title: Mechanistic Study of the Effect of Inorganic Sodium Nitrate on Cardiac and Skeletal Muscle Metabolic Efficiency in Patients With Hypertrophic Cardiomyopathy
Inorganic nitrate, which is found at high levels in green leafy vegetables, is reduced to nitrite by bacteria in the mouth, swallowed, and absorbed in the stomach into the blood. Studies have shown that increasing the blood levels of nitrite improves the way that muscles use oxygen and energy during exercise, and potentially blood flow.
Some people (~1 in 500) suffer from a type of genetic heart condition known as hypertrophic cardiomyopathy (HCM). This condition means that the muscle in the heart does not use energy well and becomes larger than average, meaning that they have to tap into the heart's 'energy reserves'. It is not known if nitrite has the same beneficial effects on heart muscle as on other muscles in the body. Our study will explore the mechanism by which nitrite may improve the function and energy status of the heart in HCM.
- Conditions
- Cardiomyopathy, Hypertrophic
- Being tested
- Sodium Nitrate, Placebo, Phosphorous Magnetic Resonance Spectroscopy, Exercise Stress Transthoracic Echocardiogram
- Medical subject headings
- Cardiomyopathy, Hypertrophic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium NitrateDrug
Single dose of 14mmol oral inorganic sodium nitrate
PlaceboDrug
Single dose of oral matching placebo
Phosphorous Magnetic Resonance SpectroscopyDiagnostic test
On the first visit day of this arm, participants will be lie inside an MRI scanner to take pictures of the heart. The thigh muscle will then be imaged before, during, and after kicking exercises.
Exercise Stress Transthoracic EchocardiogramDiagnostic test
On the second visit day of this arm, participants will be asked to lie, semi-erect, on an exercise bed for up to 90 minutes. The echocardiogram will be performed at rest and during peak exercise. The exercise will be in the form of a pedal bike. The exercise levels will be worked out from an upright bicycle exercise test completed by the participants prior to randomization.
| Study group | Role | What they receive |
|---|---|---|
| Sodium Nitrate | Active comparator | Following entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion. Receives: Drug: Sodium Nitrate; Diagnostic Test: Phosphorous Magnetic Resonance Spectroscopy; Diagnostic Test: Exercise Stress Transthoracic Echocardiogram |
| Placebo | Placebo comparator | Following entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion. Receives: Drug: Placebo; Diagnostic Test: Phosphorous Magnetic Resonance Spectroscopy; Diagnostic Test: Exercise Stress Transthoracic Echocardiogram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac Energetic Status
Change in cardiac PCr/ATP ratio on phosphorus MRS between inorganic sodium nitrate and placebo
Measured: 3 hours post dose of drug or placebo
Secondary outcomes (4)
Skeletal Muscle Mitochondrial Oxidative Capacity/Energetic Status
Change in PCr recovery half-time on dynamic phosphorus MRS between inorganic sodium nitrate and placebo
Measured: 3.5 hours post dose of drug or placebo
Cardiac Diastolic and Systolic Function on exercise
Change in measures of diastolic and systolic function on transthoracic echocardiogram at submaximal exercise between inorganic sodium nitrate and placebo
Measured: 3 hours post dose of drug or placebo
Cardiac Diastolic and Systolic Function at rest
Change in measures of diastolic and systolic function on transthoracic echocardiogram at rest between inorganic sodium nitrate and placebo
Measured: 3 hours post dose of drug or placebo
Plasma levels of Nitrate/Nitrite/NOx
Change in blood plasma levels of Nitrate/Nitrite/NOx between inorganic sodium nitrate and placebo
Measured: 3 hours post dose of drug or placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2017
- Study startNov 2017 (estimated)
- Primary completionDec 2018 (estimated)
- Study completionJan 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiomyopathy, HypertrophicStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This is a placebo-controlled, random-order mechanistic study of oral inorganic sodium nitrate versus placebo in cross-over fashion in patients with non obstructive hypertrophic cardiomyopathy and exercise limitation.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of East Anglia
- Sponsor type
- University, hospital or other
- Collaborators
- Norfolk and Norwich University Hospitals NHS Foundation Trust, British Medical Research Council
- Responsible party
- Sponsor
- Investigators
- Michael P Frenneaux, MD, Study chair, University of East AngliaSunil V Nair, MD, Principal investigator, Norfolk and Norwich University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03251287
- Sponsor's protocol ID
- 201323
- Status last verified
- Aug 2017
- First submitted
- 11 Aug 2017
- Last updated
- 25 Oct 2017
- 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 25 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistic Study of the Effect of Inorganic Sodium Nitrate on Cardiac and Skeletal Muscle Metabolic Efficiency in Patients With Hypertrophic Cardiomyopathy
- ClinicalTrials.gov ID
- NCT03251287
- Acronym / sponsor ID
- 201323
- Conditions
- Cardiomyopathy, Hypertrophic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University of East AngliaUniversity, hospital or other
- Collaborators
- Norfolk and Norwich University Hospitals NHS Foundation Trust, British Medical Research Council
- Study start
- Nov 2017 (estimated)
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Jan 2019 (estimated)
- First posted
- 16 Aug 2017 (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.
Inorganic nitrate, which is found at high levels in green leafy vegetables, is reduced to nitrite by bacteria in the mouth, swallowed, and absorbed in the stomach into the blood. Studies have shown that increasing the blood levels of nitrite improves the way that muscles use oxygen and energy during exercise, and potentially blood flow.
Some people (~1 in 500) suffer from a type of genetic heart condition known as hypertrophic cardiomyopathy (HCM). This condition means that the muscle in the heart does not use energy well and becomes larger than average, meaning that they have to tap into the heart's 'energy reserves'. It is not known if nitrite has the same beneficial effects on heart muscle as on other muscles in the body. Our study will explore the mechanism by which nitrite may improve the function and energy status of the heart in HCM.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a placebo-controlled, random-order mechanistic study of oral inorganic sodium nitrate versus placebo in cross-over fashion in patients with non obstructive hypertrophic cardiomyopathy and exercise limitation.
| Arm | Type | Receives |
|---|---|---|
| Sodium Nitrate | Active comparator | Drug: Sodium Nitrate, Diagnostic Test: Phosphorous Magnetic Resonance Spectroscopy, Diagnostic Test: Exercise Stress Transthoracic EchocardiogramFollowing entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion. |
| Placebo | Placebo comparator | Drug: Placebo, Diagnostic Test: Phosphorous Magnetic Resonance Spectroscopy, Diagnostic Test: Exercise Stress Transthoracic EchocardiogramFollowing entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female, aged between 18 and 80 years.
- Able to provide informed consent.
- Able to understand basic instructions in English.
- A diagnosis of hypertrophic cardiomyopathy based on conventional transthoracic echocardiogram guidelines: left ventricular wall thickness >1.5cm in the absence of sufficient alternative cause.
- Exercise limited by symptoms on exertion (NYHA Class II symptoms or greater).
Key exclusion criteria (8 listed)
- Significant medical, surgical or psychiatric disease that in the opinion of the patient's attending physician would affect subject safety or influence the study outcome.
- Contraindications for undergoing MRI.
- Hypotension with a systolic blood pressure <90mmHg.
- Severe anaemia with a plasma haemoglobin level <8.0g/dL.
- Known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD deficiency measured at screening in males of African, Asian or Mediterranean decent.
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 |
|---|---|---|
| Sodium NitrateSingle dose of 14mmol oral inorganic sodium nitrate | Drug | Sodium Nitrate |
| PlaceboSingle dose of oral matching placebo | Drug | Placebo |
| Phosphorous Magnetic Resonance SpectroscopyOn the first visit day of this arm, participants will be lie inside an MRI scanner to take pictures of the heart. The thigh muscle will then be imaged before, during, and after kicking exercises. | Diagnostic test | Placebo, Sodium Nitrate |
| Exercise Stress Transthoracic EchocardiogramOn the second visit day of this arm, participants will be asked to lie, semi-erect, on an exercise bed for up to 90 minutes. The echocardiogram will be performed at rest and during peak exercise. The exercise will be in the form of a pedal bike. The exercise levels will be worked out from an upright bicycle exercise test completed by the participants prior to randomization. | Diagnostic test | Placebo, Sodium Nitrate |
Primary outcome
Cardiac Energetic Status
Time frame: 3 hours post dose of drug or placebo
Change in cardiac PCr/ATP ratio on phosphorus MRS between inorganic sodium nitrate and placebo
4 secondary outcomes
Skeletal Muscle Mitochondrial Oxidative Capacity/Energetic Status
Time frame: 3.5 hours post dose of drug or placebo
Cardiac Diastolic and Systolic Function on exercise
Time frame: 3 hours post dose of drug or placebo
Cardiac Diastolic and Systolic Function at rest
Time frame: 3 hours post dose of drug or placebo
Plasma levels of Nitrate/Nitrite/NOx
Time frame: 3 hours post dose of drug or placebo
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2017.
- 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.
Michael P Frenneaux, MD study chair
University of East Anglia
Sunil V Nair, MD principal investigator
Norfolk and Norwich University Hospitals NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sodium Nitrate, Phosphorous Magnetic Resonance Spectroscopy and Exercise Stress Transthoracic Echocardiogram in people with Cardiomyopathy, Hypertrophic, run by University of East Anglia 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 7 inclusion and 8 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 Oct 2017. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Brodie L Loudon, MBBS (44(0) 1603 591 216, b.loudon@uea.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiac Energetic Status (time frame: 3 hours post dose of drug or placebo). 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 Oct 2017.