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

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).

Study Overview

• Status: Recruiting
• Conditions: Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Other: PRIME; Other: COMBO

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 92
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ben Stephenson; Phone Number: 434-243-8677; Email: bls4qq@virginia.edu

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia, Department of Kinesiology
      • Principal Investigator: Jason Allen, PhD
      • Contact: Ben Stephenson; Phone Number: 434-243-8677; Email: bls4qq@virginia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 61 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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 <45%.
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRIME + COMBO; PRIME training (Phase 1), followed by 8 weeks of progressive whole-body COMBO training.	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.; Other Names: Exercise; Other: 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.; Other Names: Exercise
Other: COMBO only; 4 weeks of standard progressive whole-body aerobic plus resistance training (COMBO) followed by 8 weeks continued COMBO training.	Other: 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.; Other Names: Exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VO2peak	Change in cardiorespiratory fitness (peak oxygen consumption [V̇O2peak]) after 12 weeks of training. The primary null hypothesis will test if mean change in V̇O2peak 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 V̇O2peak 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscular fitness	Evaluated using 1 repetition maximal strength [1RM] measured in kg units	40- weeks
Physical Function	Evaluated by the Senior Fitness Test scores [SFT], measured in percentile units.	40- weeks

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: National Institutes of Health (NIH); National Institute on Aging (NIA)
• Investigators: Principal Investigator: Jason Allen, PhD, University of Virginia

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 1, 2022
• First Posted (Actual): November 8, 2022

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: VO2peak; HFrEF
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: HSR220112; 1R01AG075556-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• 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