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

Long QT Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00588965
• Other study ID #: IRB07-00418
• Secondary ID: NIH grant, GCRC
• Status: Completed
• Phase: N/A
• First received: December 26, 2007
• Last updated: July 29, 2013
• Start date: August 2007
• Est. completion date: December 2008

Study information

• Verified date: July 2013
• Source: MetroHealth Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Cardiac Repolarization
• Long QT Syndrome

Intervention

Drug:
• Placebo
Placebo will be given 1 pill daily for a week, then 2 pills daily, followed by the exercise test.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
MetroHealth Medical Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	QTc Response to Exercise on Versus Off Beta-blocker.	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).	2 weeks on each treatment then exercise test	No
Secondary	Tpeak-end Interval (Tpe)	Tpeak-end interval was measured at rest, exercise, and recovery on placebo and on propranolol.	Measured after 2 weeks on each intervention	No