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

Study Description

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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	Not Applicable

Study Design

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Study Type :	Interventional (Clinical Trial)
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 :	August 2007
Actual Primary Completion Date :	December 2008
Actual Study Completion Date :	December 2008

Arms and Interventions

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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

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Primary Outcome Measures :

1. QTc Response to Exercise on Versus Off Beta-blocker. [ Time Frame: 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) [ Time Frame: Measured after 2 weeks on each intervention ]
   Tpeak-end interval was measured at rest, exercise, and recovery on placebo and on propranolol.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 55 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

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

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Sponsors and Collaborators

MetroHealth Medical Center

Investigators

Principal Investigator:	Elizabeth S Kaufman, MD	MetroHealth Medical Center

More Information

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

Keywords provided by Elizabeth S. Kaufman, MD, MetroHealth Medical Center:

QT interval; beta-blocker; exercise; electrocardiogram; repolarizaton

Additional relevant MeSH terms:

Long QT Syndrome; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Pathologic Processes; Propranolol	Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents