Lifestyle and Pharmacological Interventions in Hypertrophic Cardiomyopathy

NCT05366101 | Completed Phase 2

• 1 other identifier: 252015
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 1

Brief Summary

The overall aim of this project is to establish potential benefits of a novel lifestyle (physical activity and dietary nitrate) and pharmacological (angiotensin receptor neprilysin inhibitor) interventions in patients with hypertrophic cardiomyopathy (HCM). HCM is the most common genetic cardiovascular disease with a broad spectrum of disease severity. Angiotensin receptor neprilysin inhibitor reduces death, hospitalisation, and may improve cardiac function and exercise tolerance in heart failure. Exercise training is associated with a significant increase in exercise tolerance, but appear to have limited effect on measures of cardiac morphology or function in patients with HCM. Dietary supplementation with inorganic nitrate (i.e. concentrated nitrate-rich beetroot juice) improves exercise capacity, vasodilatation and cardiac output reserves while reduces arterial wave reflections, which are linked to left ventricular diastolic dysfunction and remodelling. Using a five-centre, open label, three-arm, pilot design, the present study will evaluate the effect of lifestyle (physical activity and dietary supplementation with inorganic nitrate) and pharmacological (angiotensin receptor neprilysin inhibitor sacubitril / valsartan) interventions in patients with HCM. The Aim is to examine whether these interventions improve functional capacity, clinical phenotypic characteristics, and quality of life in patients with HCM.

Conditions

Hypertrophic Cardiomyopathy

Keywords

Lifestyle; ARNI; Exercise tolerance

Outcome Measures

Primary Outcomes (1)

• Peak Oxygen Consumption (ml/kg/min)

  Change in peak oxygen consumption (ml/kg/min) post intervention

  4 months

Secondary Outcomes (5)

• Left atrial diameter (mm)

  4 months

• Left atrial volume index (mL/m2)

  4 months

• Left ventricular outflow tract velocity (m/sec)

  4 months

• Anaerobic threshold (ml/kg/min)

  4 months

• Quality of Life score

  4 months

Study Arms (3)

Lifestyle

ACTIVE COMPARATOR

Lifestyle intervention will consist of two integrated components i.e. physical activity and dietary supplementation with inorganic nitrate. The physical activity component aims to increase daily physical activity level by at least 2000 steps/day from baseline (e.g. walking for approximately 30 minutes), at least 5-7 days per week. The second component of the lifestyle intervention is a dietary supplementation with inorganic nitrate. A single dose of inorganic nitrate given in the form of concentrated nitrate-rich beetroot juice (NO3-, BEET IT Sport, James White Drinks Ltd., Ipswich, UK) containing 6 mmol of NO3- in 70 ml bottle.

Behavioral: Lifestyle

Sacubitril/Valsartan

ACTIVE COMPARATOR

Angiotensin receptor neprilysin inhibitor Sacubitril / Valsartan: The treatment period begins on day 1 with initial dosing of sacubitril/valsartan, followed by uptitration every 2 to 4 weeks to the target dose of 97/103 mg twice daily. 3 doses of sacubitril/valsartan available throughout the study are 24/26 mg, 49/51 mg, and 97/103 mg, each taken by mouth twice daily. If the patient discontinues the study medication, the patient is advised to return to the clinic for an end-of-study visit. Patients undergo treatment for 4 months.

Drug: Sacubitril/Valsartan

Usual Care

NO INTERVENTION

The participants in control group do not undertake lifestyle or sacubitril / valsartan intervention.

Interventions

Sacubitril/Valsartan DRUG

Sacubitril / Valsartan as a pharmacological agent shall be studied to verify its effects on cardiac morphology and physiology of hypertrophic cardiomyopathy patients.

Also known as: Pharmacological

Sacubitril/Valsartan

Lifestyle BEHAVIORAL

A 4-month lifestyle intervention will consist of two integrated components i.e. physical activity and dietary supplementation with inorganic nitrate. The physical activity component aims to increase daily physical activity level by at least 2000 steps/day from baseline (e.g. walking for approximately 30 minutes), at least 5-7 days per week. The second component of the lifestyle intervention is a dietary supplementation with inorganic nitrate. A single dose of inorganic nitrate given in the form of concentrated nitrate-rich beetroot juice (NO3-, BEET IT Sport, James White Drinks Ltd., Ipswich, UK) containing 6 mmol of NO3- in 70 ml bottle.

Also known as: Physical acitivity and dietary nitrate

Lifestyle

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of obstructive and/or non-obstructive hypertrophic cardiomyopathy.
• Agreement to be a participant in the study protocol and willing/able to return for follow-up.
• Able to provide written informed consent

You may not qualify if:

• Less than 3 months post septal reduction therapy (surgery or catheter based intervention)
• Clinical decompensation in the previous 3 months, defined as New York Heart Association class IV congestive heart failure symptoms.
• Resting blood pressure greater than 180/100 mm Hg.
• Systolic blood pressure lower than 100 mmHg
• Hypotensive response to exercise testing (≥20 mmHg decrease of systolic blood pressure from baseline blood pressure or an initial increase in systolic blood pressure followed by a decrease of systolic blood pressure ≥20 mmHg).
• Use of angiotensin converting Enzyme inhibitors or angiotensin receptor blockers.
• Resting left ventricular outflow tract gradient \> 50 mm Hg.
• Left ventricular ejection fraction of less than 50% by echocardiography.
• Implanted pacemaker or cardiodefibrilator in the last 3 months or scheduled.
• Renal insufficiency with a glomerular filtration rate of less than 30 mL/min per 1.73m2.
• Present or planned pregnancy.
• Life expectancy less than 12 months.
• Body mass index \>40 kg/m2.
• A history of exercise induced syncope or ventricular arrhythmias.
• Inability to exercise due to orthopaedic or other non-cardiovascular limitations.

Sponsors & Collaborators

• Newcastle-upon-Tyne Hospitals NHS Trust: lead
• University Hospital Regensburg: collaborator
• Assistance Publique - Hôpitaux de Paris: collaborator
• Azienda Ospedaliero-Universitaria Careggi: collaborator
• Institute of Cardiovascular Diseases, Vojvodina: collaborator

Study Sites (1)

Newcastle NHS

Newcastle, United Kingdom

Location

Related Publications (19)

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MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Interventions

sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

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

Study Officials

• Djordje Jakovljevic, PhD

  Faculty of Medical Sciences, Newcastle University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 1, 2019
• First Posted: May 9, 2022
• Study Start: April 1, 2019
• Primary Completion: February 28, 2022
• Study Completion: March 31, 2022
• Last Updated: May 9, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: January 2022, for five years
• Access Criteria: Data will be available upon request to a principal investigator.

Locations

GB (1)