Nitrite in Hypertrophic Cardiomyopathy (HCM) Study

NCT03251287 | Unknown Phase 1

• 1 other identifier: 201323
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cardiomyopathy, Hypertrophic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Skeletal Muscle Mitochondrial Oxidative Capacity/Energetic Status

  3.5 hours post dose of drug or placebo

• Cardiac Diastolic and Systolic Function on exercise

  3 hours post dose of drug or placebo

• Cardiac Diastolic and Systolic Function at rest

  3 hours post dose of drug or placebo

• Plasma levels of Nitrate/Nitrite/NOx

  3 hours post dose of drug or placebo

Study Arms (2)

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.

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.

Drug: Placebo; Diagnostic Test: Phosphorous Magnetic Resonance Spectroscopy; Diagnostic Test: Exercise Stress Transthoracic Echocardiogram

Interventions

Sodium Nitrate DRUG

Single dose of 14mmol oral inorganic sodium nitrate

Sodium Nitrate

Placebo DRUG

Single dose of oral matching placebo

Placebo

Phosphorous Magnetic Resonance Spectroscopy 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.

Placebo; Sodium Nitrate

Exercise Stress Transthoracic Echocardiogram 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; Sodium Nitrate

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of East Anglia: lead
• Norfolk and Norwich University Hospitals NHS Foundation Trust: collaborator
• British Medical Research Council: collaborator

Study Sites (1)

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, Norfolk, NR4 7UY, United Kingdom

RECRUITING

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Interventions

sodium nitrate

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Study Officials

• Michael P Frenneaux, MD

  University of East Anglia

  STUDY CHAIR

• Sunil V Nair, MD

  Norfolk and Norwich University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brodie L Loudon, MBBS

CONTACT

44(0) 1603 591 216; b.loudon@uea.ac.uk

Michael P Frenneaux, MD

CONTACT

44(0) 1603 593 061; m.frenneaux@uea.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 11, 2017
• First Posted: August 16, 2017
• Study Start: November 1, 2017
• Primary Completion: December 1, 2018
• Study Completion: January 1, 2019
• Last Updated: October 25, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)