PRIME HFrEF: Novel Exercise for Older Patients With Heart Failure With Reduced Ejection Fraction

Heart Failure With Reduced Ejection Fraction Clinical Trial

Official title:

PRIME HFrEF: Novel Exercise for Older Patients With Heart Failure With Reduced Ejection Fraction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05609097
• Other study ID #: HSR220112
• Secondary ID: 1R01AG075556-01A
• Status: Recruiting
• Phase: N/A
• Start date: April 14, 2023
• Est. completion date: March 31, 2027

Study information

• Verified date: May 2023
• Source: University of Virginia
• Contact: Emily Guy, B.S
• Phone: 434-243-8677
• Email: ejg9rb[@]virginia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is trying to find out whether performing a hybrid aerobic-resistance exercise training program (titled PRIME: Peripheral Remodeling via Intermittent Muscular Exercise) results in better health outcomes than the traditional exercise training program (called COMBO) that is used in individuals with heart failure with reduced ejection fraction (HFrEF). Participants will be randomized (like the flip of a coin) to either PRIME (investigational) or the traditional exercise program (standard of care).

Description:

This study is a two-arm, prospective randomized clinical trial with participants randomized, in a 1:1 ratio to 4 weeks of either standard progressive whole-body aerobic plus resistance training (COMBO) or PRIME training (Phase 1), followed by 8 weeks of progressive whole-body COMBO assigned to all participants (Phase 2). The objective of this study is to determine whether PRIME exercise training can outperform traditional (COMBO) exercise training to improve outcomes in HFrEF patients. The study aims to test 92 HFrEF patients (46 randomized to PRIME and 46 to COMBO training) over a 5-year period. Data will be collected at each visit and patients will return for a 6-month follow up from the date of the final visit.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 92
• Est. completion date: March 31, 2027
• Est. primary completion date: November 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.

• Subjects may be of either sex with age > 65 years.

• Subjects must be diagnosed with HFrEF as per established echocardiographic criteria (New York Heart Association Class II-III) with an ejection fraction <40%.

• Cardiologist approve after thorough chart review and physical examination

• Hemoglobin of at least 10.0 g/dL

Exclusion Criteria:

• Progressive worsening of exercise tolerance or dyspnea at rest or on exertion over previous 3-5 days

• Significant ischemia at low exercise intensities (<2 METS or ~50 W)

• Uncontrolled diabetes (HbA1c >10%)

• Acute systemic illness of fever

• Recent embolism (in the 6 weeks)

• Deep Vein Thrombophlebitis

• Active pericarditis or myocarditis

• Severe aortic stenosis (aortic valve area <1.0 cm2)

• Regurgitant valvular heart disease requiring surgery

• Myocardial infarction within previous 3 weeks

• New onset atrial fibrillation (in the last 4 weeks)

• Resting Heart Rate >120bpm

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

Other:
• PRIME
PRIME is a a 'hybrid' aerobic-resistance (cardio and weights) program designed to target all major muscle groups and address the muscle limitations responsible for reduced fitness in the elderly. This occurs by minimizing the central limitations to more traditional exercise by delivering an ideal exercise stimulus to muscles in a way in which the heart is not a limiting factor. Each exercise involves contractions of specific isolated muscle groups with a moderate load, defined as 40%-50% of their maximal voluntary capacity.
• COMBO
COMBO training includes both aerobic ("cardio") and resistance ("weightlifting") exercises. The aerobic component will be done on the stationary bicycle at 10-15 min duration at a target exercise intensity of 40-50% of VO2peak. This will feel like an intensity that is fairly light to somewhat hard, progressing gradually according to tolerance up to 20 mins. Intensity will be adjusted so that the difficulty remains in the target zone. The resistance component involves eight exercises, two sets of 10 repetitions, initially prescribed at 50-60% 1 repetition max. Subject will lift about half of their predicted maximal strength, 10 times, on 2 separate occasions with a rest between. Thereafter, the difficulty will be increased by approximately 10% when difficulty drops below the target range.

Locations

Country	Name	City	State
United States	University of Virginia, Department of Kinesiology	Charlottesville	Virginia

Sponsors (3)

Lead Sponsor	Collaborator
University of Virginia	National Institute on Aging (NIA), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (6)

Allen JD, Robbins JL, Vanbruggen MD, Credeur DP, Johannsen NM, Earnest CP, Pieper CF, Johnson JL, Church TS, Ravussin E, Kraus WE, Welsch MA. Unlocking the barriers to improved functional capacity in the elderly: rationale and design for the "Fit for Life trial". Contemp Clin Trials. 2013 Sep;36(1):266-75. doi: 10.1016/j.cct.2013.07.007. Epub 2013 Jul 27. — View Citation

Allen JD, Vanbruggen MD, Johannsen NM, Robbins JL, Credeur DP, Pieper CF, Sloane R, Earnest CP, Church TS, Ravussin E, Kraus WE, Welsch MA. PRIME: A Novel Low-Mass, High-Repetition Approach to Improve Function in Older Adults. Med Sci Sports Exerc. 2018 May;50(5):1005-1014. doi: 10.1249/MSS.0000000000001518. — View Citation

Angadi SS, Jarrett CL, Sherif M, Gaesser GA, Mookadam F. The effect of exercise training on biventricular myocardial strain in heart failure with preserved ejection fraction. ESC Heart Fail. 2017 Aug;4(3):356-359. doi: 10.1002/ehf2.12149. Epub 2017 Mar 16. — View Citation

Angadi SS, Mookadam F, Lee CD, Tucker WJ, Haykowsky MJ, Gaesser GA. High-intensity interval training vs. moderate-intensity continuous exercise training in heart failure with preserved ejection fraction: a pilot study. J Appl Physiol (1985). 2015 Sep 15;119(6):753-8. doi: 10.1152/japplphysiol.00518.2014. Epub 2014 Sep 4. — View Citation

Rickli H, Kiowski W, Brehm M, Weilenmann D, Schalcher C, Bernheim A, Oechslin E, Brunner-La Rocca HP. Combining low-intensity and maximal exercise test results improves prognostic prediction in chronic heart failure. J Am Coll Cardiol. 2003 Jul 2;42(1):116-22. doi: 10.1016/s0735-1097(03)00502-3. — View Citation

Shoemaker MJ, Curtis AB, Vangsnes E, Dickinson MG. Triangulating Clinically Meaningful Change in the Six-minute Walk Test in Individuals with Chronic Heart Failure: A Systematic Review. Cardiopulm Phys Ther J. 2012 Sep;23(3):5-15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	VO2peak	Change in cardiorespiratory fitness (peak oxygen consumption [V?O2peak]) after 12 weeks of training. The primary null hypothesis will test if mean change in V?O2peak after 12 weeks of training is the same for subjects who initially undergo 4 weeks of PRIME before undergoing 8 weeks of progressive whole-body COMBO, versus subjects who undergo the whole 12 weeks of progressive COMBO. The alternative hypothesis is that the mean change in V?O2peak after 12 weeks of training is not the same for subjects who initially undergo 4 weeks of PRIME training before undergoing 8 weeks of progressive COMBO, versus subjects who undergo the whole 12 weeks of progressive COMBO. Secondary endpoints include blood pressure, vascular function [arterial stiffness, endothelial function (FMD)] muscle characteristics and histochemistry, blood chemistry, physical fitness testing, quality of life questionnaires, and adherence.	12 weeks
Secondary	Muscular fitness	Evaluated using 1 repetition maximal strength [1RM] measured in kg units	40- weeks
Secondary	Physical Function	Evaluated by the Senior Fitness Test scores [SFT], measured in percentile units.	40- weeks