Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects

• Sponsor: MetroHealth Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00588965
• Collaborator: (none)
• Enrollment: 36
• Arms: 2
• Duration (Months): 16

Study Details

Study Description

Brief Summary

Background. In congenital long QT syndrome type 1 (LQT1), episodes of ventricular tachycardia are usually triggered by exercise and can be prevented in most patients by beta-blocker therapy. In addition, LQT1 associated with a normal resting QT interval can be unmasked by the abnormal QT response to exercise testing (failure of the QT interval to shorten normally). Preliminary data from our laboratory show that the exercise QT intervals of patients with LQT1 are partially normalized by beta-blocker therapy. It is still currently not known if beta-blockers modify the QT/heart rate relationship (a primary effect on repolarization) or if the "normalizing" effect is due to the inability of subjects on beta-blockers to attain sufficiently high workloads (due to reduced heart rate) for prolongation to occur. Moreover, the physiologic response of the exercise QT interval to beta-blockers in healthy control subjects is not known.

Objective. The objective of this study is to define the impact of beta-blocker therapy on the QT response to exercise and recovery in normal subjects.

Methods. Approximately 36 healthy adult subjects age-matched to previously studied LQT1 subjects will undergo 1) screening history, 2) two weeks of beta-blocker therapy ending in an exercise test, and 3) two weeks of placebo therapy ending in an exercise test. Beta blocker and placebo will be given in random order in a double-blind fashion. The QT response to exercise and recovery will be compared between drug-free and beta-blocker-treated states. These data will be compared to those previously collected for LQT1 subjects.

Implications. These results will provide new information about the effect of beta-blocker therapy on repolarization parameters in normal subjects, and will provide a context in which to interpret the previous findings that beta-blocker administration modifies the QT response to exercise in LQT1 subjects.

Condition or Disease	Intervention/Treatment	Phase
Long QT Syndrome; Cardiac Repolarization	Drug: Placebo; Drug: Propranolol LA	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1 Subjects are assigned to placebo.	Drug: Placebo; Placebo will be given 1 pill daily for a week, then 2 pills daily, followed by the exercise test.
Active Comparator: 2 Subjects will take propranolol LA 80 mg daily for one week then 160 mg for one week followed by the exercise test.	Drug: Propranolol LA; Subjects will receive propranolol LA 80 mg one pill daily for 1 week then 2 pills daily for 1 week followed by exercise test.

Outcome Measures

Primary Outcome Measures

1. QTc Response to Exercise on Versus Off Beta-blocker. [2 weeks on each treatment then exercise test]

   To minimize the effect of heart rate on QT, QT was measured at heart rates between 100 and 110 beats per minute during exercise (on and off beta-blocker) and during recovery (on and off beta-blocker).

Secondary Outcome Measures

1. Tpeak-end Interval (Tpe) [Measured after 2 weeks on each intervention]

   Tpeak-end interval was measured at rest, exercise, and recovery on placebo and on propranolol.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy normal adults, age- and gender-matched to previously studied LQT1 subjects

Exclusion Criteria:

• Cardiac disease

• Diabetes

• Hypertension

• Severe allergic reaction

• Asthma requiring treatment

• Use of medications other than oral contraceptives, acetaminophen, nonsteroidal anti-inflammatory drugs, or synthroid or other thyroid medications

• Pregnancy (subjects will be asked if they are pregnant)

• Inability to sign informed consent

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• MetroHealth Medical Center

Investigators

• Principal Investigator: Elizabeth S Kaufman, MD, MetroHealth Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Elizabeth S. Kaufman, MD, Professor, Case Western Reserve University, MetroHealth Medical Center
• ClinicalTrials.gov Identifier: NCT00588965
• Other Study ID Numbers: IRB07-00418; NIH grant, GCRC MO1 RR000080
• First Posted: Jan 9, 2008
• Last Update Posted: Jul 30, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Elizabeth S. Kaufman, MD, Professor, Case Western Reserve University, MetroHealth Medical Center: QT interval; beta-blocker; exercise; electrocardiogram; repolarizaton
• Additional relevant MeSH terms: Long QT Syndrome; Propranolol

Study Results

Participant Flow

Arm/Group Title	All Participants
Arm/Group Description	All participants were randomized to one of 2 sequences, in which they received either propranolol first, then placebo, or placebo first, then propranolol.
Period Title: Overall Study
STARTED	35
COMPLETED	35
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Subjects
Arm/Group Description	Subjects will take propranolol LA 80 mg or placebo daily for one week then propranolol LA 160 mg for one week or 2 placebo pills, followed by the exercise test. The participants will be randomized to one of 2 sequences: placebo first or propranolol first.
Overall Participants	35
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	35 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32 (12)
Sex: Female, Male (Count of Participants)
Female	20 57.1%
Male	15 42.9%
Region of Enrollment (participants) [Number]
United States	35 100%

Outcome Measures

1. Primary Outcome

Title	QTc Response to Exercise on Versus Off Beta-blocker.
Description	To minimize the effect of heart rate on QT, QT was measured at heart rates between 100 and 110 beats per minute during exercise (on and off beta-blocker) and during recovery (on and off beta-blocker).
Time Frame	2 weeks on each treatment then exercise test

Outcome Measure Data

Analysis Population Description

Please note that this was a crossover study. There were 35 subjects and each subject completed both the placebo and beta-blocker arm.

Arm/Group Title	Placebo	Propranolol
Arm/Group Description
Measure Participants	35	35
During exercise	320 (17)	317 (16)
During recovery	317 (13)	315 (14)

2. Secondary Outcome

Title	Tpeak-end Interval (Tpe)
Description	Tpeak-end interval was measured at rest, exercise, and recovery on placebo and on propranolol.
Time Frame	Measured after 2 weeks on each intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Propranolol
Arm/Group Description
Measure Participants	35	35
Rest	74 (13)	72 (13)
Peak Exercise	69 (13)	61 (11)
Recovery	77 (19)	68 (14)

Adverse Events

Arm/Group Title	Placebo		Propranolol
Arm/Group Description	Subjects are assigned to placebo.		Subjects will take propranolol LA 80 mg daily for one week then 160 mg for one week followed by the exercise test.
All Cause Mortality
	Placebo		Propranolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Propranolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Propranolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.