Clinical trial NCT01127061: Study of Exercise Training in Hypertrophic Cardiomyopathy
Official title: A Randomized Trial of Moderate Intensity Exercise Training in Hypertrophic Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiomyopathy, Hypertrophic
Keywords: Hypertrophic Cardiomyopathy
Exercise
Oxygen consumption
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Stanford University
First posted: 2010-05-20
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The investigators propose a pilot randomized controlled trial to determine the safety and potential benefits of moderate intensity exercise in patients with hypertrophic cardiomyopathy. The investigators hypotheses are that exercise parameters derived from a baseline cardiopulmonary exercise test will target an appropriately safe level of exercise intensity that will not cause significant arrhythmias or exacerbate symptoms and that exercise training for 4 months will result in significant improvements in peak oxygen consumption (peak VO2) and quality of life, with neutral effects on the clinical characteristics.

Detailed description: The goal of this randomized clinical pilot trial is to establish the safety profile and potential benefits of moderate intensity exercise in patients with hypertrophic cardiomyopathy (HCM). Participation in competitive athletics is associated with an increased risk of sudden cardiac death (SCD) in individuals with structural heart disease, including HCM. This has appropriately led to the establishment of national guidelines based on expert opinion that discourage participation in high intensity competitive sports, burst exertion (e.g., sprinting), or isometric exercise (e.g., heavy lifting). Non-competitive, low to moderate intensity exercise is allowable, although many physicians and HCM patients are still understandably apprehensive. Data on the safety of a recreational exercise program, and how to gauge appropriate intensity level, are desperately needed so that HCM patients can reap the well established health benefits of regular physical activity. Limited, but compelling animal data suggest that moderate intensity exercise is not only safe, but may also prevent or even reverse cardiac hypertrophy, fibrosis, myocellular disarray, and apoptosis associated with HCM. There are no published studies on exercise in patients with HCM, although large clinical trials in heart failure have shown exercise training to be safe, to improve peak VO2 and quality of life, and to lower cardiovascular mortality. The pilot randomized control trial proposed here is the first to determine the safety of moderate intensity exercise training and explore its potential benefits in patients with HCM.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years and ≤ 80.
* Diagnosis of HCM, defined by the presence of unexplained left-ventricular hypertrophy \> 13 mm in any wall segment.
* Agreement to be a participant in the study protocol and willing/able to return for follow-up.

Exclusion Criteria:

* History of exercise-induced syncope or arrhythmias (ventricular tachycardia or non-sustained ventricular tachycardia).
* Medically refractory left ventricular outflow tract obstruction being evaluated for septal reduction therapy.
* Less than 3 months post septal reduction therapy (surgery or catheter based intervention).
* Hypotensive response to exercise (\> 20 mm Hg drop in systolic blood pressure from peak blood pressure to post exercise blood pressure).
* Pregnancy.
* Implantable Cardioverter-Defibrillator (ICD) placement in last 3 months or scheduled.
* Left ventricular systolic dysfunction (left ventricular ejection fraction \< 55% by echocardiography).
* Worsening clinical status in the last 3 months, advanced heart failure (New York Heart Association class IV symptoms) or angina (Canadian Cardiovascular Society class IV symptoms).
* Life expectancy less than 12 months.
* Inability to exercise due to orthopedic or other non-cardiovascular limitations.
* Unwillingness to refrain from competitive sports, burst activity, or heavy isometric exercise for the duration of the study.

Primary outcomes:
measure: Change in Peak Oxygen Consumption (Peak VO2)
timeFrame: At study Enrollment and 4 months later
Secondary outcomes:
Other outcomes:
measure: Change in Quality of Life
timeFrame: At study enrollment and 4 months later
measure: Change in Concentration of Brain Natriuretic Peptide (BNP)
timeFrame: At study enrollment and 4 months later
measure: Change in Scar Volume
timeFrame: At study enrollment and 4 months later
measure: Change in Systolic Function as Measured by Left Ventricular Ejection Fraction.
timeFrame: At study enrollment and 4 months later
measure: Change in Degree of Left Ventricular Outflow (LVOT) Obstruction.
timeFrame: At study enrollment and 4 months later
measure: Change in Maximal Left Ventricle Wall Thickness
timeFrame: At study enrollment and 4 months later
measure: Change in Diastolic Function
timeFrame: At study Enrollment and 4 months later
measure: Change in Left Ventricular Mass Index
timeFrame: At study enrollment and 4 months later
measure: Change in Left Ventricular End Diastolic Volume Index
timeFrame: At study enrollment and 4 months later
measure: Change in Left Ventricular End Systolic Volume Index
timeFrame: At study enrollment and 4 months later
measure: Change in Left Atrial Size
timeFrame: At study enrollment and 4 months later
measure: Change in Left Atrial Volume Index
timeFrame: At study enrollment and 4 months later
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Ann Arbor
country: United States
facility: University of Michigan Cardiovascular Center
state: Michigan
Study officials:
affiliation: University of Michigan
name: Sara Saberi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Saberi S, Wheeler M, Bragg-Gresham J, Hornsby W, Agarwal PP, Attili A, Concannon M, Dries AM, Shmargad Y, Salisbury H, Kumar S, Herrera JJ, Myers J, Helms AS, Ashley EA, Day SM. Effect of Moderate-Intensity Exercise Training on Peak Oxygen Consumption in Patients With Hypertrophic Cardiomyopathy: A Randomized Clinical Trial. JAMA. 2017 Apr 4;317(13):1349-1357. doi: 10.1001/jama.2017.2503.