Study of Exercise Training in Hypertrophic Cardiomyopathy (RESET-HCM)

• ClinicalTrials.gov Identifier: NCT01127061
• Recruitment Status: Completed
• First Posted: May 20, 2010
• Results First Posted: February 15, 2019
• Last Update Posted: February 15, 2019
• Sponsor: University of Michigan
• Collaborator: Stanford University
• Information provided by (Responsible Party): Sara Saberi, University of Michigan

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cardiomyopathy, Hypertrophic	Behavioral: Exercise training	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 136 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Investigator who randomized participants was blinded to participant PHI. Investigators who interpreted all data and assessed outcomes were masked to randomization status.
• Primary Purpose: Supportive Care
• Official Title: A Randomized Trial of Moderate Intensity Exercise Training in Hypertrophic Cardiomyopathy
• Actual Study Start Date: April 2010
• Actual Primary Completion Date: September 2015
• Actual Study Completion Date: November 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Exercise Training; Participants in the exercise group will undergo 4 months of training, 4-7 days per week with a minimum of 20 minutes per day. The protocol will be custom designed in consultation with an exercise physiologist based on data from the initial cardiopulmonary stress test. Exercise regimen will begin at a low level of intensity then increase in duration and training intensity to a goal of 60 minutes a day and 70% of the heart rate reserve during the 1st month of the study protocol with maintenance of the program thereafter. There is no need to come to a participating site for actually doing the exercise regimen. No strength training or burst activity will be prescribed and all activities will fall well within the recommended national guidelines for recreational exercise.	Behavioral: Exercise training; 4 months of exercise training that is custom-designed based on individual cardiopulmonary stress test data. Regimen starts at low intensity (60% of heart rate reserve) and frequency (20 minutes, 3 days per week) and increases with a goal of 70% of heart rate reserve and exercising 60 minutes 4-7 days per week.
No Intervention: Usual Activity; Participants in this group are not restricted in their activities. They simply are not guided in their physical activities by the study team. At the end of the 4 month study period, they will also receive an individualized exercise prescription for personal use.

Outcome Measures

Primary Outcome Measures :

1. Change in Peak Oxygen Consumption (Peak VO2) [ Time Frame: At study Enrollment and 4 months later ]
   Cardiopulmonary exercise testing was performed at study enrollment and termination (4 months apart). Peak VO2 was measured at each time point in each subject and change in peak VO2 over time was calculated. The change in Peak VO2 was compared between the study arms.

Other Outcome Measures:

1. Change in Quality of Life [ Time Frame: At study enrollment and 4 months later ]

   Quality of life (QOL) questionnaires (Minnesota Living With Heart Failure Questionnaire, MLHF; Quick Inventory of Depressive Symptomatology-Self Report, QIDS-SR16; and the 36-Item Short-Form Health Survey Version 2, SF-36v2) were administered at study enrollment and termination (4 months later). Change over time was compared between study arms.

   MLHF: range, 0-105; higher scores indicate worse QOL QIDS-SR16: range, 0-27; higher scores indicate more severe depression SF-36v2: 8 subscales and 2 component summary scores; range, 1-100; lower scores indicate more disability; minimal clinically important difference, 3 to 5 points

2. Change in Concentration of Brain Natriuretic Peptide (BNP) [ Time Frame: At study enrollment and 4 months later ]
   Blood will be drawn to evaluate BNP at study enrollment and termination (4 months later). Change over time was compared between study arms.
3. Change in Scar Volume [ Time Frame: At study enrollment and 4 months later ]
   Cardiac MRI was performed in all patients without implantable devices/claustrophobia requiring sedation at study enrollment and termination (4 months later). Scar volume was calculated as total delayed gadolinium enhancement mass at each time interval. Change over time was compared between study arms.
4. Change in Systolic Function as Measured by Left Ventricular Ejection Fraction. [ Time Frame: At study enrollment and 4 months later ]
   Echocardiography was performed at study enrollment and termination. Left ventricular ejection fraction was visually estimated on each echocardiogram. Change over time was compared by study arm assignment.
5. Change in Degree of Left Ventricular Outflow (LVOT) Obstruction. [ Time Frame: At study enrollment and 4 months later ]
   Cardiopulmonary exercise testing in combination with echocardiography was performed at study enrollment and termination (4 months). Peak left ventricular outflow gradients were obtained at rest, with Valsalva and after exercise at each time point. The change over time was compared by study arm assignment.
6. Change in Maximal Left Ventricle Wall Thickness [ Time Frame: At study enrollment and 4 months later ]
   Magnitude or distribution of cardiac hypertrophy or left ventricular dimensions were a pre-specified outcome. Maximal left ventricle (LV) wall thickness (mm) was measured by cardiac MRI performed at study enrollment and termination (4 months later) and change over time was compared between study arms. Cardiac MRI was only be performed in those who do not have implantable devices or claustrophobia significant enough to require sedation.
7. Change in Diastolic Function [ Time Frame: At study Enrollment and 4 months later ]
   Diastolic function was assessed at each time point and categorized as indeterminate diastolic function, grade I diastolic dysfunction and grade II-III diastolic dysfunction, according to American Society of Echocardiography criteria. Number of participants whose findings fell into each category was calculated and % change over time was compared between study arms. Indeterminate indicates diastolic function could not be accurately categorized. Grade I diastolic dysfunction indicates least severe in terms of outcome measure and Grade III, most severe.
8. Change in Left Ventricular Mass Index [ Time Frame: At study enrollment and 4 months later ]
   Magnitude or distribution of cardiac hypertrophy or left ventricular dimensions were a pre-specified outcome. Left ventricular mass index was measured by cardiac MRI at study enrollment and termination (4 months later) and change over time was compared between study arms. Cardiac MRI was only be performed in those who do not have implantable devices or claustrophobia significant enough to require sedation.
9. Change in Left Ventricular End Diastolic Volume Index [ Time Frame: At study enrollment and 4 months later ]
   Magnitude or distribution of cardiac hypertrophy or left ventricular dimensions were a pre-specified outcome. Left ventricular end diastolic volume index was measured by cardiac MRI at study enrollment and termination (4 months later) and change over time was compared between study arms. Cardiac MRI was only be performed in those who do not have implantable devices or claustrophobia significant enough to require sedation.
10. Change in Left Ventricular End Systolic Volume Index [ Time Frame: At study enrollment and 4 months later ]
    Magnitude or distribution of cardiac hypertrophy or left ventricular dimensions were a pre-specified outcome. Left ventricular end systolic index was measured by cardiac MRI at study enrollment and termination (4 months later) and change over time was compared between study arms. Cardiac MRI was only be performed in those who do not have implantable devices or claustrophobia significant enough to require sedation.
11. Change in Left Atrial Size [ Time Frame: At study enrollment and 4 months later ]
    Magnitude or distribution of cardiac hypertrophy or left ventricular dimensions were a pre-specified outcome. Left atrial size was measured by echocardiography at study enrollment and termination (4 months later) and change over time was compared between study arms.
12. Change in Left Atrial Volume Index [ Time Frame: At study enrollment and 4 months later ]
    Magnitude or distribution of cardiac hypertrophy or left ventricular dimensions were a pre-specified outcome. Left atrial volume index was measured by echocardiography at study enrollment and termination (4 months later) and change over time was compared between study arms.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

Stanford University

Stanford, California, United States, 94305

United States, Michigan

University of Michigan Cardiovascular Center

Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

University of Michigan

Stanford University

Investigators

• Principal Investigator: Sara Saberi, MD; University of Michigan

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Erratum In: JAMA. 2017 May 23;317(20):2134.

• Responsible Party: Sara Saberi, Principal Investigator, University of Michigan
• ClinicalTrials.gov Identifier: NCT01127061
• Other Study ID Numbers: RESET-HCM
• First Posted: May 20, 2010
• Results First Posted: February 15, 2019
• Last Update Posted: February 15, 2019
• Last Verified: October 2018

Keywords provided by Sara Saberi, University of Michigan:

Hypertrophic Cardiomyopathy; Exercise; Oxygen consumption

Additional relevant MeSH terms:

Cardiomyopathies; Cardiomyopathy, Hypertrophic; Hypertrophy; Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases