Clinical trial NCT00588965: Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
Official title: Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Long QT Syndrome
Cardiac Repolarization
Keywords: QT interval
beta-blocker
exercise
electrocardiogram
repolarizaton
Lead sponsor: MetroHealth Medical Center
Sponsor class: OTHER
First posted: 2008-01-09
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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

Primary outcomes:
measure: QTc Response to Exercise on Versus Off Beta-blocker.
timeFrame: 2 weeks on each treatment then exercise test
Secondary outcomes:
measure: Tpeak-end Interval (Tpe)
timeFrame: Measured after 2 weeks on each intervention
Other outcomes:
Locations:
Study officials:
affiliation: MetroHealth Medical Center
name: Elizabeth S Kaufman, MD
role: PRINCIPAL_INVESTIGATOR
References: