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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Elizabeth S. Kaufman, MD, MetroHealth Medical Center
ClinicalTrials.gov Identifier:
NCT00588965
First received: December 26, 2007
Last updated: July 29, 2013
Last verified: July 2013
  Purpose

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 Intervention
Long QT Syndrome
Cardiac Repolarization
Drug: Placebo
Drug: Propranolol LA

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects

Resource links provided by NLM:


Further study details as provided by MetroHealth Medical Center:

Primary Outcome Measures:
  • QTc Response to Exercise on Versus Off Beta-blocker. [ Time Frame: 2 weeks on each treatment then exercise test ] [ Designated as safety issue: No ]
    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:
  • Tpeak-end Interval (Tpe) [ Time Frame: Measured after 2 weeks on each intervention ] [ Designated as safety issue: No ]
    Tpeak-end interval was measured at rest, exercise, and recovery on placebo and on propranolol.


Enrollment: 36
Study Start Date: August 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00588965

Sponsors and Collaborators
MetroHealth Medical Center
Investigators
Principal Investigator: Elizabeth S Kaufman, MD MetroHealth Medical Center
  More Information

No publications provided

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
Study First Received: December 26, 2007
Results First Received: May 1, 2012
Last Updated: July 29, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by 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
Adrenergic beta-Antagonists
Propranolol
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on August 01, 2014