Back to results

Nitrite in Hypertrophic Cardiomyopathy (HCM) Study

Primary Purpose

Cardiomyopathy, Hypertrophic

Status

Unknown status

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Sodium Nitrate

Placebo

Phosphorous Magnetic Resonance Spectroscopy

Exercise Stress Transthoracic Echocardiogram

About this trial

This is an interventional other trial for Cardiomyopathy, Hypertrophic

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Norfolk and Norwich University Hospitals NHS Foundation TrustRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Sodium Nitrate

Placebo

Arm Description

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.

Outcomes

Primary Outcome Measures

Cardiac Energetic Status

Change in cardiac PCr/ATP ratio on phosphorus MRS between inorganic sodium nitrate and placebo

Secondary Outcome Measures

Skeletal Muscle Mitochondrial Oxidative Capacity/Energetic Status

Change in PCr recovery half-time on dynamic phosphorus MRS between inorganic sodium nitrate and 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

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

Plasma levels of Nitrate/Nitrite/NOx

Change in blood plasma levels of Nitrate/Nitrite/NOx between inorganic sodium nitrate and placebo

Full Information

NCT ID

NCT03251287

First Posted

August 11, 2017

Last Updated

October 24, 2017

Sponsor

University of East Anglia

Collaborators

Norfolk and Norwich University Hospitals NHS Foundation Trust, British Medical Research Council

1. Study Identification

Unique Protocol Identification Number

NCT03251287

Brief Title

Nitrite in Hypertrophic Cardiomyopathy (HCM) Study

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Unknown status

Study Start Date

November 2017 (Anticipated)

Primary Completion Date

December 2018 (Anticipated)

Study Completion Date

January 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of East Anglia

Collaborators

Norfolk and Norwich University Hospitals NHS Foundation Trust, British Medical Research Council

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cardiomyopathy, Hypertrophic

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

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

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

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.

Allocation

Randomized

Enrollment

18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Sodium Nitrate

Arm Type

Active Comparator

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Sodium Nitrate

Intervention Description

Single dose of 14mmol oral inorganic sodium nitrate

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Single dose of oral matching placebo

Intervention Type

Diagnostic Test

Intervention Name(s)

Phosphorous Magnetic Resonance Spectroscopy

Intervention Description

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

Intervention Name(s)

Exercise Stress Transthoracic Echocardiogram

Intervention Description

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.

Primary Outcome Measure Information:

Title

Cardiac Energetic Status

Description

Change in cardiac PCr/ATP ratio on phosphorus MRS between inorganic sodium nitrate and placebo

Time Frame

3 hours post dose of drug or placebo

Secondary Outcome Measure Information:

Title

Skeletal Muscle Mitochondrial Oxidative Capacity/Energetic Status

Description

Change in PCr recovery half-time on dynamic phosphorus MRS between inorganic sodium nitrate and placebo

Time Frame

3.5 hours post dose of drug or placebo

Title

Cardiac Diastolic and Systolic Function on exercise

Description

Change in measures of diastolic and systolic function on transthoracic echocardiogram at submaximal exercise between inorganic sodium nitrate and placebo

Time Frame

3 hours post dose of drug or placebo

Title

Cardiac Diastolic and Systolic Function at rest

Description

Change in measures of diastolic and systolic function on transthoracic echocardiogram at rest between inorganic sodium nitrate and placebo

Time Frame

3 hours post dose of drug or placebo

Title

Plasma levels of Nitrate/Nitrite/NOx

Description

Change in blood plasma levels of Nitrate/Nitrite/NOx between inorganic sodium nitrate and placebo

Time Frame

3 hours post dose of drug or placebo

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Brodie L Loudon, MBBS

Phone

44(0) 1603 591 216

b.loudon@uea.ac.uk

First Name & Middle Initial & Last Name or Official Title & Degree

Michael P Frenneaux, MD

Phone

44(0) 1603 593 061

m.frenneaux@uea.ac.uk

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael P Frenneaux, MD

Organizational Affiliation

University of East Anglia

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Sunil V Nair, MD

Organizational Affiliation

Norfolk and Norwich University Hospitals NHS Foundation Trust

Official's Role

Principal Investigator

Facility Information:

Facility Name

Norfolk and Norwich University Hospitals NHS Foundation Trust

City

Norwich

State/Province

Norfolk

ZIP/Postal Code

NR4 7UY

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Brodie L Loudon, MBBS

Phone

44(0) 1603 591 216

b.loudon@uea.ac.uk

First Name & Middle Initial & Last Name & Degree

Sunil V Nair, MD

First Name & Middle Initial & Last Name & Degree

Brodie L Loudon, MBBS

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Nitrite in Hypertrophic Cardiomyopathy (HCM) Study

We'll reach out to this number within 24 hrs