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Trial record 68 of 188 for:    GLYCOPYRROLATE

Chronotropic Incompetence in Patients With HFpEF

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ClinicalTrials.gov Identifier: NCT02524145
Recruitment Status : Completed
First Posted : August 14, 2015
Results First Posted : April 23, 2019
Last Update Posted : April 23, 2019
Sponsor:
Information provided by (Responsible Party):
Benjamin Levine, University of Texas Southwestern Medical Center

Tracking Information
First Submitted Date  ICMJE August 10, 2015
First Posted Date  ICMJE August 14, 2015
Results First Submitted Date  ICMJE December 18, 2018
Results First Posted Date  ICMJE April 23, 2019
Last Update Posted Date April 23, 2019
Study Start Date  ICMJE June 2015
Actual Primary Completion Date November 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 4, 2019)
  • Cardiac Beta-receptor Sensitivity [ Time Frame: 1 day; primary outcome was complete for each subject in 1 day ]
    Cardiac beta-receptor sensitivity will be measured by calculating slope of heart rate versus isoproterenol serum level.
  • Central Command Regulation of Heart Rate [ Time Frame: 1 day; primary outcome was complete for each subject in 1 day ]
    Heart rate response to static hand grip immediately followed by supra-systolic arm occlusion and release will determine adequacy on central command control over heart rate response during exercise.
Original Primary Outcome Measures  ICMJE
 (submitted: August 12, 2015)
  • Cardiac Beta-receptor Sensitivity [ Time Frame: 2 years ]
    Cardiac beta-receptor sensitivity will be measured by calculating slope of heart rate versus isoproterenol serum level.
  • Central Command Regulation of Heart Rate [ Time Frame: 2 years ]
    Heart rate response to static hand grip immediately followed by supra-systolic arm occlusion and release will determine adequacy on central command control over heart rate response during exercise.
Change History Complete list of historical versions of study NCT02524145 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chronotropic Incompetence in Patients With HFpEF
Official Title  ICMJE Determinants of Chronotropic Incompetence in Patients With Heart Failure and a Preserved Ejection Fraction (HFpEF)
Brief Summary The purpose of this study is to determine the mechanisms of chronotropic incompetence (inability to increase heart rate with exercise) in patients with heart failure and preserved ejection fraction (HFpEF). The investigators will test both central command regulation and cardiac beta-receptor sensitivity over control of heart rate.
Detailed Description

About half of all elderly patients with a diagnosis of congestive heart failure have apparently normal systolic function, so called "heart failure with a preserved ejection fraction" or HFpEF. To date, no effective therapy for HFpEF has been found, in part because of failure to discern key pathophysiologic pathways.

Although HFpEF is a complex disease with multiple pathophysiologic pathways leading to the phenotype of heart failure, virtually all proposed mechanisms involve some impairment of diastolic function - the inability of the heart to fill adequately at a low enough pressure to avoid congestion which during physical activity or exercise, prevent an increase in heart rate. A number of studies have purported the inability to increase heart rate (chronotropic incompetence) is responsible for the diminished exercise capacity.

Alternatively, the investigators hypothesize that the stiff, slowly relaxing heart of patients with HFpEF causes a marked elevation in pulmonary capillary pressure during exercise which leads to premature fatigue prior to achieving maximal heart rate, thus causing apparent "chronotropic incompetence".

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Heart Failure
Intervention  ICMJE
  • Other: Static Handgrip
    Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.
  • Drug: Dexmedetomidine
    Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.
    Other Name: Sympathetic blockade
  • Drug: Glycopyrrolate
    Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.
    Other Name: Parasympathetic blockade
  • Drug: Isoproterenol
    Subjects will be given dexmedetomidine to suppress sympathetic outflow to minimize sympathetic control over resting heart rate. Subjects will then be given glycopyrrolate to suppress parasympathetic tone to minimize parasympathetic control over resting heart rate. After achievement of autonomic blockade, cardiac beta receptor sensitivity will be assessed by graded infusions of isoproterenol until heart rate increases 30 beats above baseline.
    Other Name: Beta-receptor sensitivity testing
Study Arms  ICMJE
  • Active Comparator: Healthy Seniors

    Fifteen healthy senior volunteers > 60 years of age. Subjects will be healthy with no chronic medical problems and on no cardiac medications except for statins. All control subjects will have a Body Mass Index (BMI) <30, with exercise histories of less than 3 days per week of aerobic exercise.

    Intervention: Static handgrip and Autonomic Blockade (Dexmedetomidine, Glycopyrrolate, Isoproterenol)

    Interventions:
    • Other: Static Handgrip
    • Drug: Dexmedetomidine
    • Drug: Glycopyrrolate
    • Drug: Isoproterenol
  • Experimental: HFpEF

    Patients with HFpEF will provide data from their cardiologist or primary care physician that confirm the following: a) signs and symptoms of heart failure; b) an ejection fraction > 0.50; and c) objective evidence of diastolic dysfunction.

    Intervention: Static handgrip and Autonomic Blockade (Dexmedetomidine, Glycopyrrolate, Isoproterenol)

    Interventions:
    • Other: Static Handgrip
    • Drug: Dexmedetomidine
    • Drug: Glycopyrrolate
    • Drug: Isoproterenol
  • Active Comparator: Healthy Young

    Fifteen volunteers <45 yrs will be enrolled. Subjects will be healthy with no chronic medical problems and on no cardiac medications except for statins and have BMI <30.

    Intervention: Autonomic Blockade (Dexmedetomidine, Glycopyrrolate, Isoproterenol)

    Interventions:
    • Drug: Dexmedetomidine
    • Drug: Glycopyrrolate
    • Drug: Isoproterenol
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 17, 2017)
40
Original Estimated Enrollment  ICMJE
 (submitted: August 12, 2015)
45
Actual Study Completion Date  ICMJE November 15, 2017
Actual Primary Completion Date November 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Healthy Controls

Inclusion Criteria:

  • ages > 60 years
  • body mass index <30
  • absence of co-morbid conditions including hypertension, diabetes, heart failure, asthma, chronic obstructive pulmonary disease, coronary artery disease as evidenced by angina or prior myocardial infarction or cerebrovascular disease as evidenced by prior transient ischemic attack or stroke

Exclusion Criteria:

  • ages less than 60
  • body mass index >30
  • presence of co-morbid conditions including hypertension, diabetes, heart failure, asthma, chronic obstructive pulmonary disease, coronary artery disease as evidenced by angina or prior myocardial infarction or cerebrovascular disease as evidenced by prior transient ischemic attack or stroke
  • Patients with chronic orthopedic injury that might make them unable to participate in an exercise testing will also be excluded
  • Subjects unable to speak English will not be recruited because of the complex experimental studies and the need for precise communication between the volunteers and the research staff to ensure safety.

HFpEF Subjects

Inclusion Criteria:

  • Patients will be > 60 years old, male or female, all races.
  • signs and symptoms of heart failure
  • ejection fraction > 0.50
  • objective evidence of diastolic dysfunction.
  • All patients must be in sinus rhythm without a left bundle branch block at the time of study

Exclusion Criteria:

  • underlying valvular or congenital heart disease
  • restrictive or infiltrative cardiomyopathy
  • acute myocarditis
  • New York Heart Association (NYHA) Class IV congestive heart failure, or heart failure that cannot be stabilized on medical therapy
  • other condition that would limit the patient's ability to complete the protocol
  • manifest ischemic heart disease
  • Coumadin/warfarin therapy
  • Patients with chronic orthopedic injury that might make them unable to participate in an exercise testing will also be excluded
  • Subjects unable to speak English will not be recruited because of the complex experimental studies and the need for precise communication between the volunteers and the research staff to ensure safety.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02524145
Other Study ID Numbers  ICMJE UTexasSouthwestern
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Benjamin Levine, University of Texas Southwestern Medical Center
Study Sponsor  ICMJE University of Texas Southwestern Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Benjamin D Levine, MD University of Texas Southwestern Medical Center
PRS Account University of Texas Southwestern Medical Center
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP