Inhibition of Small Conductance Calcium-Activated Potassium Current: A New Therapeutic Approach for Atrial Fibrillation
Indiana University
Summary
"Afib" is a common irregular heartbeat. Afib can cause stroke, blood clots, dementia and death. Medicines used to treat Afib often do not work well and can cause serious side effects. Clinicians need medicines that work better for Afib. Medicines for Afib work by blocking a current in the heart called a potassium current. There is a newer potassium current called IKas that can contribute to Afib. A medicine called ondansetron is used to keep people with cancer from getting sick to their stomach and throwing up. The investigators have found that ondansetron blocks IKas, and the investigators think that this means that ondansetron may work well to treat Afib. So, in this study the investigators want to find out if ondansetron can: 1) Reduce the amount of time that people have Afib, and 2) Slow down the heart rate when people have Afib. The investigators will study 80 people who are scheduled to have an AF ablation. Several weeks prior to undergoing the ablation procedure, these AF patients will be assigned by chance (like flipping a coin) to one of two groups: ondansetron 8 mg by mouth twice daily or a sugar pill (placebo), which they will take for 28 days. The people in the study will not know whether they are receiving ondansetron or placebo. The investigators will find out if ondansetron reduces the percentage of time that people are in Afib. Also, the investigators will find out if ondansetron slows the heart rate while people are having Afib. The investigators will compare the people in the study who take ondansetron with the people in the study who take placebo. This research will help the investigators to find out if ondansetron can be used as a medicine for people who have Afib.
Description
Atrial fibrillation (AF) is a common arrhythmia associated with symptoms, stroke, systemic embolism, heart failure, dementia, and mortality. Guideline-recommended strategies for conversion to and maintenance of sinus rhythm (SR) and ventricular rate (VR) control are of limited efficacy and/or are poorly tolerated. There is a critical need for safer, more effective alternatives for AF drug therapy. The apamin-sensitive small-conductance calcium-activated potassium (SK) ion current (IKas) is important for repolarization in the atria and pulmonary vein muscle sleeves. IKas also contributes to sin…
Eligibility
- Age range
- 18–100 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Men and women 18-100 years of age * ECG-verified AF and/or atrial flutter requiring elective catheter ablation * Receiving guideline-recommended anticoagulation (if CHA2DS2-VASc score is 0 (men) or 1 (women), anticoagulation can be omitted) Exclusion Criteria: * Women of childbearing potential * Subject reported syncope of unknown origin within the previous 6 months * Diagnosis of active thyrotoxicosis * Diagnosis AF from reversible noncardiac causes * Diagnosis of acutely decompensated heart failure * Left ventricular ejection fraction less than or equal to 20% * N…
Interventions
- DrugOndansetron 8mg
Ondansetron 8 mg orally twice daily for 28 days
- DrugPlacebo
Matched placebo orally twice daily for 28 days
Locations (3)
- Indiana Clinical Research CenterIndianapolis, Indiana
- Indiana University Health Methodist HospitalIndianapolis, Indiana
- Purdue UniversityIndianapolis, Indiana