Nitrite in Hypertrophic Cardiomyopathy (HCM) Study

Cardiomyopathy, Hypertrophic Clinical Trial

Official title:

Mechanistic Study of the Effect of Inorganic Sodium Nitrate on Cardiac and Skeletal Muscle Metabolic Efficiency in Patients With Hypertrophic Cardiomyopathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03251287
• Other study ID #: 201323
• Status: Recruiting
• Phase: Phase 1
• First received: August 11, 2017
• Last updated: October 24, 2017
• Start date: November 2017
• Est. completion date: January 2019

Study information

• Verified date: August 2017
• Source: University of East Anglia
• Contact: Brodie L Loudon, MBBS
• Phone: 44(0) 1603 591 216
• Email: b.loudon[@]uea.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: January 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Hypertrophy

Intervention

Drug:
• Sodium Nitrate
Single dose of 14mmol oral inorganic sodium nitrate
• Placebo
Single dose of oral matching placebo

Diagnostic Test:
• 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.
• 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.

Locations

Country	Name	City	State
United Kingdom	Norfolk and Norwich University Hospitals NHS Foundation Trust	Norwich	Norfolk

Sponsors (3)

Lead Sponsor	Collaborator
University of East Anglia	British Medical Research Council, Norfolk and Norwich University Hospitals NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac Energetic Status	Change in cardiac PCr/ATP ratio on phosphorus MRS between inorganic sodium nitrate and placebo	3 hours post dose of drug or placebo
Secondary	Skeletal Muscle Mitochondrial Oxidative Capacity/Energetic Status	Change in PCr recovery half-time on dynamic phosphorus MRS between inorganic sodium nitrate and placebo	3.5 hours post dose of drug or placebo
Secondary	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	3 hours post dose of drug or placebo
Secondary	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	3 hours post dose of drug or placebo
Secondary	Plasma levels of Nitrate/Nitrite/NOx	Change in blood plasma levels of Nitrate/Nitrite/NOx between inorganic sodium nitrate and placebo	3 hours post dose of drug or placebo