RiLuzole to Reduce Atrial FIb Study Using Holter Monitoring

NCT05292209 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB_00144866
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atrial Fibrillation Paroxysmal

Keywords

Atrial Fibrillation Paroxysmal, Riluzole, Holter Monitoring

Outcome Measures

Primary Outcomes (2)

• Episodes of Tachycardia

  Number of episodes of atrial fibrillation in 1 month between riluzole 50mg BID versus matching placebo;

  30 Days

• Time to First Tachycardia Episode

  Time to first episode of atrial fibrillation between riluzole 50mg BID and placebo

  30 Days

Secondary Outcomes (2)

• Safety of Riluzole Pro-Arrhythmia

  30 Days

• Safety of Riluzole Neutropenia

  30 days

Study Arms (2)

Active

EXPERIMENTAL

Riluzole 50mg BID

Drug: Riluzole 50 MG

Control

PLACEBO COMPARATOR

Placebo Matching Double-Dummy Pills

Drug: Riluzole 50 MG

Interventions

Riluzole 50 MG DRUG

Riluzole 50mg tablets

Active; Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Utah: lead
• Ohio State University: collaborator

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84112-5820, United States

RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Riluzole

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Mark A Munger, Pharm.D.

CONTACT

801-581-6165; mmunger@hsc.utah.edu

John Kirk

CONTACT

801-585-2944; john.kirk@hsc.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double Blind Double Dummy
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: A prospective, double-blind, randomized, placebo-controlled, two-arm study design in patients with PAF

Study Record Dates

• First Submitted: March 14, 2022
• First Posted: March 23, 2022
• Study Start: June 15, 2022
• Primary Completion: October 30, 2024
• Study Completion: October 30, 2024
• Last Updated: November 24, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Within 30 days after completion of last patient
• Access Criteria: De-identified data only

Locations

US (1)