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

Not Applicable
Completed
Conditions
Cardiac Repolarization
Long QT Syndrome
Interventions
Registration Number
NCT00588965
Lead Sponsor
MetroHealth Medical Center
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
36
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
2Propranolol LASubjects will take propranolol LA 80 mg daily for one week then 160 mg for one week followed by the exercise test.
1PlaceboSubjects are assigned to placebo.
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
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.

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