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Muscle Afferent Feedback Effects in Patients With Heart Failure

Primary Purpose

Chronic Heart Failure

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Muscle Contraction with Metabolite Solution Administration
Sponsored by
University of Utah
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Chronic Heart Failure

Eligibility Criteria

20 Years - 79 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Heart Failure 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

Heart Failure 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

Healthy Control Inclusion Criteria:

  • 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

Healthy Control Exclusion Criteria:

  • 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

Sites / Locations

  • George E Wahlen Vetern Affairs Medical Center
  • Veterans Affairs Salt Lake City Heath Care System

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Heart Failure Patients

Control Participants

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Elbow Flexor Maximal Voluntary Contraction in newton-meters

Secondary Outcome Measures

Full Information

First Posted
July 29, 2013
Last Updated
January 4, 2018
Sponsor
University of Utah
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1. Study Identification

Unique Protocol Identification Number
NCT01919918
Brief Title
Muscle Afferent Feedback Effects in Patients With Heart Failure
Official Title
Muscle Afferent Feedback Effects in Patients With Heart Failure: The Development of Central Fatigue
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
January 3, 2018 (Actual)
Study Completion Date
January 3, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Utah

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Heart Failure

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
144 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Heart Failure Patients
Arm Type
Other
Arm Description
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.
Arm Title
Control Participants
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Muscle Contraction with Metabolite Solution Administration
Other Intervention Name(s)
adenosine triphosphate, lactate, and protons with phosphate buffer
Intervention Description
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
Primary Outcome Measure Information:
Title
Elbow Flexor Maximal Voluntary Contraction in newton-meters
Time Frame
2 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Heart Failure 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 Heart Failure 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 Healthy Control Inclusion Criteria: 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 Healthy Control Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Markus Amann, PhD
Organizational Affiliation
University of Utah
Official's Role
Principal Investigator
Facility Information:
Facility Name
George E Wahlen Vetern Affairs Medical Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84148
Country
United States
Facility Name
Veterans Affairs Salt Lake City Heath Care System
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84148
Country
United States

12. IPD Sharing Statement

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Muscle Afferent Feedback Effects in Patients With Heart Failure

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