Muscle Afferent Feedback Effects in Patients With Heart Failure

NCT ID: NCT01919918

Last Updated: 2018-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2018-01-03

Brief Summary

The purpose of the study is to find out more about the mechanism by which neural feedback from the working muscle affects the development of central fatigue during exercise. Subjects with chronic heart failure (HF) and healthy subject counterparts will be tested to determine the mechanisms accounting for the premature fatigue characterizing HF patients during physical activity.

Detailed Description

A substantial part in limiting exercise and/or physical activity in humans results from the development of peripheral and central fatigue during physical activity. Peripheral fatigue comprises biochemical changes within the metabolic milieu of the working muscle leading to an attenuated response to neural excitation, while central fatigue comprises a failure of the central nervous system to drive motoneurons.

Patients with HF have overactive group III/IV muscle afferents and an exaggerated development of central fatigue during physical activity that is not explained by their reduced physical conditioning or cardiac insufficiency caused by their failing heart. The exact mechanisms accounting for the exaggerated central fatigue in HF remains elusive, however, the development of central fatigue during exercise has recently been linked to signaling by group III/IV muscle afferents. This makes the heightened neural feedback in HF a likely candidate for these patients' increased susceptibility to central fatigue.

Lower pH, increased lactate and increased adenosine triphosphate has been shown to activate group III/IV afferents in a physiological manner and thus induce, in a rested and unfatigued muscle, the intramuscular milieu associated with moderate to heavy exercise. The objective of this study is to quantitate and compare the sensitivity of group III/IV afferents and associated effects on central fatigue in HF patients and healthy controls when skeletal muscle is subject to controlled lower pH, increased lactate and increased adenosine triphosphate.

Conditions

Chronic Heart Failure

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Heart Failure Patients

Patients with heart failure will undergo intervention of muscle contraction with metabolite solution administration. Maximal voluntary muscle contraction exercise with varying metabolite solution administration of adenosine triphosphate, lactate, and protons with phosphate buffer.

Group Type: OTHER

Muscle Contraction with Metabolite Solution Administration

Intervention Type: DRUG

Participants will perform maximal elbow flexor or knee extensor contractions before and after administration of metabolite solutions of pH 7.2, pH 7.0 and pH 6.6

Control Participants

Healthy control participants will undergo intervention of muscle contraction with metabolite solution administration. Maximal voluntary muscle contraction exercise with varying metabolite solution administration of adenosine triphosphate, lactate, and protons with phosphate buffer.

Group Type: OTHER

Muscle Contraction with Metabolite Solution Administration

Intervention Type: DRUG

Participants will perform maximal elbow flexor or knee extensor contractions before and after administration of metabolite solutions of pH 7.2, pH 7.0 and pH 6.6

Interventions

Muscle Contraction with Metabolite Solution Administration

Participants will perform maximal elbow flexor or knee extensor contractions before and after administration of metabolite solutions of pH 7.2, pH 7.0 and pH 6.6

Intervention Type: DRUG

Other Intervention Names

adenosine triphosphate, lactate, and protons with phosphate buffer

Eligibility Criteria

Inclusion Criteria

• Subjects with a history of stable cardiomyopathy (ischemic and non-ischemic, greater than 1 year duration, ages 20-79 years)
• New York Heart Association class I through IV symptoms
• Left ventricular ejection fraction less than 35 percent (heart failure patients with reduced left ventricular ejection fraction) or greater than 50 percent (heart failure patients with preserved left ventricular ejection fraction)
• Sedentary, no regular physical activity for at least 6 months prior
• Post-menopausal for at least 2 years and follicle stimulating hormone greater than 40

• Ages 20-75 years
• Sedentary, no regular physical activity for at least 6 months prior
• Post-menopausal for at least 2 years and follicle stimulating hormone greater than 40

Exclusion Criteria

• Patients with atrial fibrillation or heart failure believed to be secondary to atrial fibrillation
• Morbidly obese patients with a body mass index greater than 35
• Patients with uncontrolled hypertension, greater than 160/100
• Anemia with a hemoglobin less than 9
• Severe renal insufficiency (creatinine clearance less than 30 by the Cockcroft-Gault formula)
• Patients with significant non-cardiac comorbidities
• Orthopedic limitations that would prohibit them from performing the elbow-flexor exercise
• Current smoker or smoking history of 15 packs or more per year
• Women currently taking hormone replacement therapy

• History of cardiovascular related abnormalities or pulmonary abnormalities
• Morbidly obese patients with a body mass index greater than 35
• Patients with uncontrolled hypertension, greater than 160/100
• Anemia with a hemoglobin less than 9
• Orthopedic limitations that would prohibit them from performing the elbow-flexor exercise
• Current smoker or smoking history of 15 packs or more per year
• Women currently taking hormone replacement therapy

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Markus Amann

PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Markus Amann, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

George E Wahlen Vetern Affairs Medical Center

Salt Lake City, Utah, United States

Veterans Affairs Salt Lake City Heath Care System

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

62914

Identifier Type: -

Identifier Source: org_study_id