Valsartan for Attenuating Disease Evolution In Early Sarcomeric HCM



Status:Active, not recruiting
Conditions:High Cholesterol, Cardiology, Orthopedic
Therapuetic Areas:Cardiology / Vascular Diseases, Orthopedics / Podiatry
Healthy:No
Age Range:8 - 45
Updated:2/7/2018
Start Date:April 2014
End Date:July 2019

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The purpose of this trial is to determine whether treatment with valsartan will have
beneficial effect in early hypertrophic cardiomyopathy (HCM) by assessing many domains that
reflect myocardial structure, function and biochemistry.

This is a multicenter, double-blind, placebo-controlled Phase II, randomized clinical trial
to assess the safety and efficacy of valsartan in attenuating disease evolution in early HCM.
Sarcomere mutation carriers with asymptomatic or mildly symptomatic overt disease (NYHA class
I-II), and mutation carriers without left ventricular hypertrophy (LVH) will be studied.

Inclusion Criteria:

1. All subjects must have a Pathogenic or Likely Pathogenic HCM Sarcomere Mutation

a. The following categories of mutations are considered acceptable for subjects who have
previously undergone clinical genetic testing. If results are ambiguous, they will be
reviewed by the Clinical Coordinating Center to determine eligibility.

- Laboratory for Molecular Medicine (Pathogenic, Likely Pathogenic)

- Transgenomics/ PGXHealth (Class I)

- GeneDx (Disease causing; Variant; likely disease-causing; Published, disease-causing
mutation; Novel, likely disease-causing, mutation)

- Correlagen (Associated; Probably Associated)

Group 1 (Overt HCM Cohort)

1. LV wall thickness ≥12 mm and ≤25 mm or z score ≥3 and ≤18 as determined by rapid
assessment by the echocardiographic core laboratory

2. NYHA functional class I or II; no perceived or only slight limitations in physical
activities

3. No resting or provokable LV obstruction (peak gradient ≤ 30 mmHg) on
clinically-obtained Exercise Tolerance Test (ETT)-echo within the past 24 months or
transthoracic echo with Valsalva maneuver within the past 12 months

4. Age 8-45 years

5. Able to attend follow-up appointments, complete all study assessments, and provide
written informed consent

Group 2 (Preclinical HCM Cohort (G+/LVH-))

1. LV Wall Thickness <12 mm and z score <3 , as determined by rapid assessment by the
echocardiographic core laboratory

2. Age 10-25 years

3. E' z score ≤ -1.5 OR ECG abnormalities other than NSSTW changes (Q waves, T wave
inversion, repolarization changes) OR LV wall thickness z-score 1.5-2.9 combined with
LV thickness to dimension ratio ≥0.19 (as determined by rapid assessment by the
echocardiographic core laboratory)

4. Able to attend follow-up appointments, complete all study assessments, and provide
written informed consent

Subject Exclusion Criteria

1. Contraindication to angiotensin receptor blocker (ARB) administration, including
impaired renal function, hyperkalemia (serum K>5.0 mmol/L), prior history of
angioedema

2. Medical conditions associated with increased collagen turnover that may confound
interpretation of biomarkers of collagen synthesis (liver, pulmonary or renal
fibrosis, inflammatory states, cancer, trauma or surgery within 6 months of
enrollment)

3. Concomitant use of Spironolactone, Lithium, or Aliskiren, ARB or ACE-inhibitors. If
these drugs are in active use but not necessary for medical care, they may be
discontinued and baseline studies can be performed after a 2-week washout period.

4. Pregnant or breastfeeding females - Females of childbearing potential with no
effective contraceptive method (including abstinence)

5. Uncontrolled systemic HTN [persistent SBP>160 and/or DBP>90 in adult or equivalent in
children (e.g., SBP>99th or DBP>95th percentile for sex, age, and height centile based
on the American Academy of Pediatrics normal values)]

6. Obstructive physiology, defined by resting, Valsalva-provoked or exercise-induced
gradient >30mmHg within the past 24 months

7. Prior septal myectomy or alcohol septal ablation

8. Known, suspected, or symptomatic coronary artery disease or evidence of prior
myocardial infarction based on symptoms or cardiac imaging

9. More than mild valvular heart disease or clinically significant congenital heart
disease. Allowable conditions include bicuspid aortic valve without clinically
significant stenosis or regurgitation; spontaneously closed ventricular septal
defects; patent foramen ovale, small (≤ 2 mm) restrictive ventricular septal defects
with normal ventricular size, and other minor defects that are considered allowable
after [review and consensus by participating pediatric cardiologists, overall study PI
and] adjudication by the echocardiographic core laboratory.

10. Left ventricular ejection fraction (LVEF) <55%

11. Concomitant medical conditions that would preclude performance of or confound
interpretation of echocardiography, exercise testing, or CMR (e.g., renal
insufficiency, lung disease, orthopedic/rheumatologic conditions, atrial fibrillation)

12. Secondary prevention implantable cardioverter-defibrillator device (ICD; primary
prevention ICDs without a history of appropriate therapy, including shock or ATP, are
allowable).

13. Prior treatment or hospitalization for symptomatic heart failure

14. Participation in a clinical trial (except observational studies) involving
investigational medications within the previous 30 days.
We found this trial at
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sites
2049 E 100th St
Cleveland, Ohio 44106
(216) 444-2200
Principal Investigator: Harry Lever, MD
Phone: 216-444-6970
Cleveland Clinic Foundation The Cleveland Clinic (formally known as The Cleveland Clinic Foundation) is a...
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3400 N Charles St
Baltimore, Maryland 21205
410-516-8000
Principal Investigator: Anne Murphy, MD
Phone: 410-955-5987
Johns Hopkins University The Johns Hopkins University opened in 1876, with the inauguration of its...
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75 Francis street
Boston, Massachusetts 02115
(617) 732-5500
Principal Investigator: Carolyn Ho, MD
Phone: 617-732-5685
Brigham and Women's Hosp Boston’s Brigham and Women’s Hospital (BWH) is an international leader in...
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Boston, MA
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5801 South Ellis Avenue
Chicago, Illinois 60637
 773.702.1234
Principal Investigator: Amit Patel, MD
Phone: 773-702-1843
University of Chicago One of the world's premier academic and research institutions, the University of...
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South 34th Street
Philadelphia, Pennsylvania 19104
 215-590-1000
Phone: 267-425-6116
Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
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Philadelphia, PA
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500 S State St
Ann Arbor, Michigan 48109
(734) 764-1817
Principal Investigator: Sharlene Day, MD
Phone: 734-615-7917
University of Michigan The University of Michigan was founded in 1817 as one of the...
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Aurora, Colorado 80045
Principal Investigator: Matthew Taylor, MD, PhD
Phone: 303-724-1400
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Boston, Massachusetts 02115
Principal Investigator: Steven Colan, MD
Phone: 617-355-7893
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3333 Burnet Avenue
Cincinnati, Ohio 45229
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2201 West End Ave
Nashville, Tennessee 37232
(615) 322-7311
Phone: 615-936-8297
Vanderbilt University Vanderbilt offers undergraduate programs in the liberal arts and sciences, engineering, music, education...
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3451 Walnut St
Philadelphia, Pennsylvania 19104
1 (215) 898-5000
Phone: 215-615-0812
Univ of Pennsylvania Penn has a long and proud tradition of intellectual rigor and pursuit...
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660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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450 Serra Mall
Stanford, California 94305
(650) 723-2300
Principal Investigator: Euan Ashley, MD, PhD
Phone: 650-498-4900
Stanford University Stanford University, located between San Francisco and San Jose in the heart of...
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Toronto, Ontario
Principal Investigator: Harry Rakowski, MD
Phone: 416-340-4062
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