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

NCT05609097 | Recruiting DMC

• 2 other identifiers: HSR2201121R01AG075556-01A1
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Heart Failure With Reduced Ejection Fraction

Keywords

HFrEF; VO2peak

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Muscular fitness

  40- weeks

• Physical Function

  40- weeks

Study Arms (2)

PRIME + COMBO

EXPERIMENTAL

PRIME training (Phase 1), followed by 8 weeks of progressive whole-body COMBO training.

Other: PRIME; Other: COMBO

COMBO only

OTHER

4 weeks of standard progressive whole-body aerobic plus resistance training (COMBO) followed by 8 weeks continued COMBO training.

Other: COMBO

Interventions

PRIME OTHER

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.

Also known as: Exercise

PRIME + COMBO

COMBO OTHER

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.

Also known as: Exercise

COMBO only; PRIME + COMBO

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Virginia: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Virginia, Department of Kinesiology

Charlottesville, Virginia, 22908, United States

RECRUITING

Related Publications (6)

• 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.

  PMID: 29232316 BACKGROUND

• 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.

  PMID: 22993497 BACKGROUND

• 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.

  PMID: 23900005 BACKGROUND

• 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.

  PMID: 12849670 BACKGROUND

• 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.

  PMID: 28772048 BACKGROUND

• 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.

  PMID: 25190739 BACKGROUND

MeSH Terms

Interventions

Exercise

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Jason Allen, PhD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ben Stephenson

CONTACT

434-243-8677; bls4qq@virginia.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principle investigator

Model Details: Prospective randomized open-label blinded endpoint (PROBE) parallel-group design. Participants will be randomized to PRIME or COMBO training for an initial four weeks (Phase 1). Following this, all participants will complete an additional eight weeks of COMBO training (Phase 2). Participants will be randomized in a 1:1 ratio by an independent statistician James Patrie (permuted block randomization with block size of 4, stratified by gender), with treatment allocation revealed after baseline exercise testing. Outcomes will be assessed at baseline, four weeks and eight weeks and 36 weeks (exploratory aim 5) by a blinded assessor (UVA SoM Exercise Core Laboratory).

Study Record Dates

• First Submitted: November 1, 2022
• First Posted: November 8, 2022
• Study Start: April 14, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: June 6, 2025

Record last verified: 2025-06

Locations

US (1)