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Lifestyle and Pharmacological Interventions in Hypertrophic Cardiomyopathy (SILICOFCM)

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ClinicalTrials.gov Identifier: NCT03832660
Recruitment Status : Recruiting
First Posted : February 6, 2019
Last Update Posted : July 23, 2019
Sponsor:
Collaborators:
Azienda Ospedaliero-Universitaria Careggi
University Hospital Regensburg
Institute for Cardiovascular Diseases of Vojvodina
University of Belgrade
Information provided by (Responsible Party):
Djordje Jakovljevic, Newcastle University

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.

Condition or disease Intervention/treatment Phase
Hypertrophic Cardiomyopathy Behavioral: Lifestyle Drug: Sacubitril/Valsartan Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical and Genetic Determinants of Disease Progression and Response to Lifestyle and Pharmacological Interventions in Patients With Hypertrophic Cardiomyopathy
Actual Study Start Date : May 3, 2019
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : November 30, 2021


Arm Intervention/treatment
Active Comparator: Lifestyle
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
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.
Other Name: Physical acitivity and dietary nitrate

Active Comparator: Sacubitril/Valsartan
Sacubitril / Valsartan as a pharmacological agent shall be studied to verify its effects on cardiac morphology and physiology of hypertrophic cardiomyopathy patients.
Drug: Sacubitril/Valsartan
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.
Other Name: Pharmacological

No Intervention: Usual Care
The participants in control group do not undertake lifestyle or sacubitril / valsartan intervention.



Primary Outcome Measures :
  1. Peak Oxygen Consumption (ml/kg/min) [ Time Frame: 4 months ]
    Change in exercise tolerance i.e. peak oxygen consumption and anaerobic threshold post intervention


Secondary Outcome Measures :
  1. Left ventricular mass (grams) [ Time Frame: 4 months ]
    The size of the left ventricle

  2. LVOT obstruction [ Time Frame: 4 months ]
    Degree of left ventricular outflow tract obstruction.

  3. LVEF (%) [ Time Frame: 4 months ]
    Left ventricular ejection fraction

  4. Minnesota Living with Heart Failure questionnaire [ Time Frame: 4 months ]
    Quality of Life (score range from 0 to 105)

  5. SF36 questionnaire [ Time Frame: 4 months ]
    Quality of Life RAND 36-Item Health Survey (score range from 0 to 100)

  6. E/A ratio [ Time Frame: 4 months ]
    Early to late filling ratio



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  • Use of other investigational drugs at the time of enrolment.
  • Any surgical or medical condition that in the opinion of the investigator may place the patient at higher risk from his/her participation in the study or is likely to prevent the patient from complying with the requirements of the study or completing the study.
  • History or presence of any other disease with a life expectancy of <3 years
  • History of noncompliance to medical regimens and patients who are considered potentially unreliable.
  • History or evidence of drug or alcohol abuse within the past 12 months.
  • History of malignancy of any organ system (other than localized basal or squamous cell carcinoma of the skin or localized prostate cancer), treated or untreated, within the past 2 years, regardless of whether there is evidence of local recurrence or metastases.
  • Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and AF or atrial flutter with a resting ventricular rate >110 beats per minute.
  • Participation in competitive or organized sport activities (such as football, basketball, rugby, hockey, etc), burst activity (such as sprinting, racket sports, etc) or heavy isometric exercise (such as body building or bench-pressing) or opposition of refraining from the same for the duration of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03832660


Contacts
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Contact: Dr Djordje G Jakovljevic +44 191 208 8257 djordje.jakovljevic@newcastle.ac.uk
Contact: Dr Guy A MacGowan +44 191 233 6161 guy.macgowan@nuth.nhs.uk

Locations
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Germany
University Hospital Regensburg Not yet recruiting
Regensburg, Germany
Contact: Dr Lars Maier       lars.maier@klinik.uni-regensburg.de   
Contact: Dr Maria Tafelmeier       maria.tafelmeier@klinik.uni-regensburg.de   
Italy
Azienda Ospedaliero Universitaria Careggi Florence Not yet recruiting
Florence, Italy
Contact: Dr Iacopo Olivotto       iacopo.olivotto@unifi.it   
Contact: Dr Fausto Barlocco       fausto.barlocco@unifi.it   
Serbia
University of Belgrade Faculty of Medicine Not yet recruiting
Belgrade, Serbia
Contact: Dr Dejana Popovic       dejanapopovic@yahoo.co.uk   
Contact: Dr Arsen Ristic       arsen.ristic@gmail.com   
Institute of Cardiovascular Diseases of Vojvodina Recruiting
Sremska Kamenica, Serbia
Contact: Dr Lazar Velicki       lvelicki@gmail.com   
Contact: Dr Andrej Preveden       a.preveden@gmail.com   
United Kingdom
Newcastle University, Faculty of Medical Sciences, Clinical Research Facility, Royal Victoria Infirmary; Newcastle upon Tyne Hospitals NHS Foundation Trust Recruiting
Newcastle Upon Tyne, England, United Kingdom, NE2
Contact: Dr Djordje G Jakovljevic    +44 191 20 88257    djordje.jakovljevic@newcastle.ac.uk   
Contact: Dr Guy A MacGowan    +44 191 233 6161    guy.macgowan@nuth.nhs.uk   
Sub-Investigator: Dr Paul Brennan         
Sub-Investigator: Dr Christopher Eggett         
Sub-Investigator: Dr Nduka Okwose         
Sponsors and Collaborators
Newcastle University
Azienda Ospedaliero-Universitaria Careggi
University Hospital Regensburg
Institute for Cardiovascular Diseases of Vojvodina
University of Belgrade
Investigators
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Principal Investigator: Dr Djordje G Jakovljevic Newcastle University Faculty of Medical Sciences, Clinical Research Facility, Newcastle upun Tyne Hospitals NHS Foundation Trust
  Study Documents (Full-Text)

Documents provided by Djordje Jakovljevic, Newcastle University:
Study Protocol  [PDF] September 14, 2018


Publications of Results:

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Responsible Party: Djordje Jakovljevic, Senior Lecturer/Associate Professor in Cardiovascular Ageing and Heart Failure, Newcastle University
ClinicalTrials.gov Identifier: NCT03832660     History of Changes
Other Study ID Numbers: 252015
First Posted: February 6, 2019    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymised individual patient data will be shared between the partners of the SILICOFCM project.
Supporting Materials: Study Protocol
Time Frame: January 2022, for five years
Access Criteria: Data will be available upon request to a principal investigator.
URL: http://silicofcm.eu

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Djordje Jakovljevic, Newcastle University:
Lifestyle
ARNI
Exercise tolerance
Additional relevant MeSH terms:
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Cardiomyopathies
Cardiomyopathy, Hypertrophic
Hypertrophy
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases
Valsartan
LCZ 696
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action