Trial Outcomes & Findings for Chronotropic Incompetence in Patients With HFpEF (NCT NCT02524145)
NCT ID: NCT02524145
Last Updated: 2020-08-06
Results Overview
Cardiac beta-receptor sensitivity will be measured by calculating slope of heart rate versus isoproterenol serum level.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
40 participants
Primary outcome timeframe
1 day; primary outcome was complete for each subject in 1 day
Results posted on
2020-08-06
Participant Flow
Recruitment initiated in June 2015 and completed October 2017. Subjects were recruited from academic medical center cardiology clinic. Healthy control subjects were recruited from the community.
Participant milestones
| Measure |
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.
Intervention: Static handgrip and Autonomic Blockade (Dexmedetomidine, Glycopyrrolate, Isoproterenol)
Static Handgrip: Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
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)
Static Handgrip: Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
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)
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
|---|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
10
|
|
Overall Study
COMPLETED
|
13
|
13
|
7
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
3
|
Reasons for withdrawal
| Measure |
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.
Intervention: Static handgrip and Autonomic Blockade (Dexmedetomidine, Glycopyrrolate, Isoproterenol)
Static Handgrip: Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
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)
Static Handgrip: Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
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)
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
3
|
Baseline Characteristics
Two senior controls, three young controls and two HFpEF subjects withdrew consent.
Baseline characteristics by cohort
| Measure |
Healthy Seniors
n=15 Participants
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.
Intervention: Static handgrip and Autonomic Blockade (Dexmedetomidine, Glycopyrrolate, Isoproterenol)
Static Handgrip: Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
HFpEF
n=15 Participants
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)
Static Handgrip: Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
Healthy Young
n=10 Participants
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)
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=15 Participants
|
0 Participants
n=15 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=40 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=15 Participants
|
6 Participants
n=15 Participants
|
10 Participants
n=10 Participants
|
17 Participants
n=40 Participants
|
|
Age, Categorical
>=65 years
|
14 Participants
n=15 Participants
|
9 Participants
n=15 Participants
|
0 Participants
n=10 Participants
|
23 Participants
n=40 Participants
|
|
Age, Continuous
|
71 years
STANDARD_DEVIATION 4 • n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
68 years
STANDARD_DEVIATION 6 • n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
31 years
STANDARD_DEVIATION 4 • n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
61 years
STANDARD_DEVIATION 17 • n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
|
Sex: Female, Male
Female
|
6 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
7 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
1 Participants
n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
14 Participants
n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
|
Sex: Female, Male
Male
|
7 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
6 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
6 Participants
n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
19 Participants
n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
1 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
1 Participants
n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
2 Participants
n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
12 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
6 Participants
n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
31 Participants
n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
2 Participants
n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
2 Participants
n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
2 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
1 Participants
n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
4 Participants
n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
|
Race (NIH/OMB)
White
|
12 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
11 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
4 Participants
n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
27 Participants
n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
0 Participants
n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent.
|
|
Region of Enrollment
United States
|
15 participants
n=15 Participants
|
15 participants
n=15 Participants
|
10 participants
n=10 Participants
|
40 participants
n=40 Participants
|
|
Exercise heart rate
|
156 beats per minute
STANDARD_DEVIATION 15 • n=13 Participants • Two senior control, three young control and two HFPEF subjects withdrew after consent.
|
117 beats per minute
STANDARD_DEVIATION 15 • n=13 Participants • Two senior control, three young control and two HFPEF subjects withdrew after consent.
|
190 beats per minute
STANDARD_DEVIATION 8 • n=7 Participants • Two senior control, three young control and two HFPEF subjects withdrew after consent.
|
148 beats per minute
STANDARD_DEVIATION 32 • n=33 Participants • Two senior control, three young control and two HFPEF subjects withdrew after consent.
|
|
Beta-receptor function
|
0.254 beats per ng/kg/min
STANDARD_DEVIATION 0.166 • n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent
|
0.156 beats per ng/kg/min
STANDARD_DEVIATION 0.133 • n=13 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent
|
0.365 beats per ng/kg/min
STANDARD_DEVIATION 0.129 • n=7 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent
|
0.239 beats per ng/kg/min
STANDARD_DEVIATION 0.163 • n=33 Participants • Two senior controls, three young controls and two HFpEF subjects withdrew consent
|
PRIMARY outcome
Timeframe: 1 day; primary outcome was complete for each subject in 1 dayCardiac beta-receptor sensitivity will be measured by calculating slope of heart rate versus isoproterenol serum level.
Outcome measures
| Measure |
Healthy Seniors
n=13 Participants
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)
Static Handgrip: Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
HFpEF
n=13 Participants
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)
Static Handgrip: Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
Healthy Young
n=7 Participants
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)
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
|---|---|---|---|
|
Cardiac Beta-receptor Sensitivity
|
0.254 beats per ng/kg/min ISO
Standard Deviation 0.166
|
0.156 beats per ng/kg/min ISO
Standard Deviation 0.133
|
0.365 beats per ng/kg/min ISO
Standard Deviation 0.129
|
PRIMARY outcome
Timeframe: 1 day; primary outcome was complete for each subject in 1 dayPopulation: Young subjects did not perform handgrip portion of the study.
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.
Outcome measures
| Measure |
Healthy Seniors
n=15 Participants
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)
Static Handgrip: Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
HFpEF
n=15 Participants
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)
Static Handgrip: Subjects will perform static handgrip at 40% of maximum voluntary contraction until fatigue.
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
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)
Autonomic Blockade: Subjects will be given dexmedetomidine and glycopyrrolate to suppress neural control over heart rate during isoproterenol infusion.
|
|---|---|---|---|
|
Central Command Regulation of Heart Rate
|
93 beats per minute
Standard Deviation 11
|
89 beats per minute
Standard Deviation 14
|
—
|
Adverse Events
Healthy Seniors
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
HFpEF
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Healthy Young
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dr. Satyam Sarma
University of Texas Southwestern Medical Center
Phone: 214-345-7111
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place