Muscle, Essential Amino Acids, and eXercise in Heart Failure (MAAX-HF)

Cost-effective Strategies to Improve Rehabilitative Outcomes for Heart Failure Patients With Preserved Ejection Fraction

Half of heart failure patients have preserved ejection fraction (HFpEF). Like patients with reduced ejection fraction (HFrEF), HFpEF patients suffer from exercise intolerance (low VO2max), which reduces physical function, quality of life, and survival. Strikingly, there is no medication proven to increase survival for HFpEF patients. Whereas exercise intolerance in HFrEF patients is the result of cardiovascular limitations, physical dysfunction in HFpEF patients is largely the result of peripheral abnormalities in skeletal muscle. Indeed, research in HFpEF patients identified that physical function and VO2peak are directly related to leg lean mass, and drugs focused on improving cardiovascular function have failed to improve VO2peak. Unfortunately, no therapy has been identified for this population that can concurrently improve cardiovascular and muscle health. The need for improved muscle therapies is reinforced by the fact that HFpEF patients are commonly older adults who are predisposed to muscle wasting. Strategic essential amino acid (EAA) ingestion has been shown to improve the adaptive response of muscle to exercise. Therefore, the investigators will determine, in HFpEF patients, the extent to which ingesting a strategic mixture of EAAs during an acute aerobic exercise training program enhances the response to this exercise strategy.

Study Overview

• Status: Terminated
• Conditions: Heart Failure, Diastolic
• Intervention / Treatment: Other: Exercise; Dietary supplement: Essential Amino Acids; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Arizona State University
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 60+ years of age
• Able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
• Diagnosed with HFpEF as per established echocardiographic criteria (New York Heart Association Class II-III).

Exclusion Criteria:

• Unstable angina, myocardial infarction in the past 4 weeks
• Uncompensated heart failure
• New York Heart Association class IV symptoms, complex ventricular arrhythmias, symptomatic severe aortic stenosis, acute pulmonary embolus, acute myocarditis, untreated high-risk proliferative retinopathy, recent retinal hemorrhage, uncontrolled hypertension, baseline blood screening abnormalities
• Medication non-compliance
• Medical / orthopedic conditions precluding exercise
• Exercise training (>2 weekly sessions of moderate to high intensity aerobic or resistance exercise)
• Subjects on anti-coagulation medication will not be eligible for the muscle biopsy procedure, but are deemed eligible for study participation if INR < 3.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Essential Amino Acid and Exercise; Participants will be provided with essential amino acids during exercise training.	Other: Exercise; Aerobic exercise performed 3/d per week during intervention; Dietary supplement: Essential Amino Acids; Mixture of 10g of essential amino acids ingested throughout intervention
Placebo Comparator: Placebo and Exercise; Participants will be provided with placebo supplement during exercise training.	Other: Exercise; Aerobic exercise performed 3/d per week during intervention; Dietary supplement: Placebo; 10g of maltodextrin ingested throughout intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in VO2max	Change in maximal Aerobic Capacity	Change from pre to after the 4 week intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Flow-mediated Dilation	Change in blood vessel function	Change from pre to after the 4 week intervention
Change in Pulse wave velocity	Change in pulse wave velocity	Change from pre to after the 4 week intervention
Change in Diastolic Function	Change in diastolic Function	Change from pre to after the 4 week intervention
Change in Skeletal Muscle mRNA expression	Change in skeletal Muscle mRNA expression	Change from pre to after the 4 week intervention

Collaborators and Investigators

• Sponsor: Arizona State University
• Collaborators: Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2017
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: October 9, 2017
• First Submitted That Met QC Criteria: October 16, 2017
• First Posted (Actual): October 17, 2017

Study Record Updates

• Last Update Posted (Actual): September 3, 2019
• Last Update Submitted That Met QC Criteria: August 29, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Diastolic
• Other Study ID Numbers: STUDY00004142

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No