Nitrite in Hypertrophic Cardiomyopathy (HCM) Study

NCT ID: NCT03251287

Last Updated: 2017-10-25

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

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-30

Study Completion Date

2019-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Cardiomyopathy, Hypertrophic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

OTHER

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
This will be a double blind study. The placebo and active treatments will appear identical and will be dispensed in identical containers. All trial patients, care providers, outcome assessors and data analysts will remain blind throughout the study.

Study Groups

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Sodium Nitrate

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.

Group Type ACTIVE_COMPARATOR

Sodium Nitrate

Intervention Type DRUG

Single dose of 14mmol oral inorganic sodium nitrate

Phosphorous Magnetic Resonance Spectroscopy

Intervention Type DIAGNOSTIC_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 Echocardiogram

Intervention Type DIAGNOSTIC_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.

Placebo

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Single dose of oral matching placebo

Phosphorous Magnetic Resonance Spectroscopy

Intervention Type DIAGNOSTIC_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 Echocardiogram

Intervention Type DIAGNOSTIC_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.

Interventions

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Sodium Nitrate

Single dose of 14mmol oral inorganic sodium nitrate

Intervention Type DRUG

Placebo

Single dose of oral matching placebo

Intervention Type DRUG

Phosphorous Magnetic Resonance Spectroscopy

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.

Intervention Type DIAGNOSTIC_TEST

Exercise Stress Transthoracic Echocardiogram

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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Norfolk and Norwich University Hospitals NHS Foundation Trust

OTHER

Sponsor Role collaborator

British Medical Research Council

OTHER_GOV

Sponsor Role collaborator

University of East Anglia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael P Frenneaux, MD

Role: STUDY_CHAIR

University of East Anglia

Sunil V Nair, MD

Role: PRINCIPAL_INVESTIGATOR

Norfolk and Norwich University Hospitals NHS Foundation Trust

Locations

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Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, Norfolk, United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Brodie L Loudon, MBBS

Role: CONTACT

Phone: 44(0) 1603 591 216

Email: [email protected]

Michael P Frenneaux, MD

Role: CONTACT

Phone: 44(0) 1603 593 061

Email: [email protected]

Facility Contacts

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Brodie L Loudon, MBBS

Role: primary

Other Identifiers

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201323

Identifier Type: -

Identifier Source: org_study_id