ASsessment Of RiLuzole To Reduce Paroxysmal Episodes of Atrial FIbrillatiON (The SOLUTION Study)

IRB_00144866

Atrial fibrillation (AF) is a growing clinical problem.1 AF is a highly dynamic condition involving episodes of sinus rhythm interspersed with periods of arrhythmia, becoming more difficult to terminate over time. AF carries a substantial cost, morbidity and mortality burden. There are two important approaches to the management of AF: 1). Controlling ventricular response rate without attempting to terminate or prevent AF (rate control), and 2). Attempting to control and maintain sinus rhythm (rhythm control).2 Current rhythm control with antiarrhythmic agents (AAD) is only moderately beneficial in restoration and maintenance of sinus rhythm but produce serious adverse events. AAD selection is limited based on the potential for pro-arrhythmia, patient's age, presence of structural heart disease, and renal or hepatic dysfunction. All AF anti-arrhythmic agents are associated with harm (number needed to harm 17-119).3 There remains an important need for development of an efficacious safe AAD for the control of AF. Recent published translational studies suggest that that neuronal-type Na+ channel blockade (nNav) with riluzole, a nNav inhibitor used to manage amyotrophic lateral sclerosis (ALS), can effectively suppress triggered atrial arrhythmias.4 In two independent retrospective cohorts, riluzole-treated ALS patients significantly lowered the incidence of new-onset AF. Riluzole is well-tolerated without evidence of pro-arrhythmia.5 Therefore, to assess riluzole's effects on the reduction of paroxysmal episodes of AF, we will conduct a prospective, randomized, placebo-controlled human study using holter monitors that offer continuous electrocardiographic monitoring pre- (1 month) and with exposure to riluzole or placebo (1 month) to determine statistically superior reductions in episodes of AF.

2022-06-15

2024-10-30

2024-10-30

Recruiting

Early phase I

78

Inclusion Criteria: * Males or Female adult patients (\> 18 years old) with a history of symptomatic AF documented electrocardiographically within \> 48 hours to 12 months before enrollment. * Is able to provide written informed consent to participate in the study and is able to understand the procedures and study requirements. * Must voluntarily sign and date an informed consent form that approved by the University of Utah IRB before the conduct of any study-specific procedure. * Will be anti-coagulated or is already anti-coagulated for planned cardioversion. * Is planned to undergo a cardioversion. * Patients who are not being treated with an anti-arrhythmic agent per their physician's treatment plan Exclusion Criteria: * Systolic BP \> 180 mmHg or Diastolic BP \> 100 mmHg; * Atrial Fibrillation due to electrolyte imbalance, hyperthyroidism, pericarditis, or other reversible illness; * NYHA FC IV Heart Failure (No ADHF Decompensation with 1 month); * Unstable Angina, AMI, coronary surgery within 3 or coronary angioplasty within 1 month of screening; * Wolff-Parkinson-White syndrome unless treated with successful ablation; * Infiltrative heart disease; * Severe valvular heart disease; * History of syncope or angina precipitated by an ventricular arrhythmia; * History of torsade de pointes; * Any polymorphic ventricular tachycardia; * Sustained monomorphic ventricular tachycardia, or cardia arrest; * Class I or III antiarrhythmic agents; * Females of childbearing age. If female, is either not of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile \[bilateral tubal ligation, bilateral oophorectomy, or hysterectomy\]) or is practicing 1 of the following medically acceptable methods of birth control for at least one full menstrual cycle prior to screening (see below), and agrees to continue with the regimen from the time of screening, throughout the entire study they are excluded; * Hormonal methods such as oral, implantable, injectable, vaginal ring, or transdermal contraceptives for a minimum of 3 full cycles (based on the subject's usual menstrual cycle period) before study medication administration * Total abstinence from sexual intercourse since the last menses before study medication administration * Intrauterine device * Double-barrier method (condoms, sponge, or diaphragm with spermicidal jellies or cream); * Aminotransferases \> 5 x ULN (Test in the last 3 months); * CYP 1A2 Potent Inhibitors including cimetidine, ciprofloxacin, enoxacin, rifampin, barbiturates, and fluvoxamine; and * Active tobacco use. (i.e., smoking)

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'A prospective, double-blind, randomized, placebo-controlled, two-arm study design in patients with PAF', 'primaryPurpose': 'PREVENTION', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': 'Double Blind Double Dummy', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 78, 'type': 'ESTIMATED'}}

2023-11-24