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

NCT ID: NCT00588965

Last Updated: 2013-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2008-12-31

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.

Conditions

Long QT Syndrome; Cardiac Repolarization

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

1

Subjects are assigned to placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

2

Subjects will take propranolol LA 80 mg daily for one week then 160 mg for one week followed by the exercise test.

Group Type: ACTIVE_COMPARATOR

Propranolol LA

Intervention Type: DRUG

Subjects will receive propranolol LA 80 mg one pill daily for 1 week then 2 pills daily for 1 week followed by exercise test.

Interventions

Placebo

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

Intervention Type: 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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

MetroHealth Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Elizabeth S. Kaufman, MD

Professor, Case Western Reserve University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elizabeth S Kaufman, MD

Role: PRINCIPAL_INVESTIGATOR

MetroHealth Medical Center

Other Identifiers

NIH grant, GCRC MO1 RR000080

Identifier Type: -

Identifier Source: secondary_id

IRB07-00418

Identifier Type: -

Identifier Source: org_study_id