Dantrolene for Ventricular Arrhythmias

Overseen By Ben M Shoemaker, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Vanderbilt University Medical Center

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 day

84 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if Dantrolene, given through an injection, can help patients with heart disease by calming overactive parts of their hearts to prevent dangerous rhythms. Dantrolene has been shown to protect the heart in various studies.

Do I need to stop taking my current medications for the trial?

The trial requires that you do not use calcium channel blockers. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is Dantrolene generally safe for humans?

The safety of Dantrolene, also known as Ryanodex, has been evaluated in various studies, and while specific data on its use for ventricular arrhythmias is limited, it is generally considered safe for human use in other conditions. However, like many drugs, it may have side effects, and its safety profile should be discussed with a healthcare provider. ^{1 2 3 4 5}

How does the drug Dantrolene differ from other treatments for ventricular arrhythmias?

Dantrolene is unique because it targets the ryanodine receptor (a protein involved in calcium release in heart cells), helping to stabilize calcium levels and reduce abnormal heart rhythms. This mechanism is different from traditional treatments, which often focus on blocking electrical signals in the heart. ^{6 7 8 9 10}

Research Team

William Stevenson, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for adults with a rapid heartbeat condition called ventricular tachycardia, who are referred for VT ablation and have structural heart disease. They must be able to consent and not have severe heart failure, morbid obesity, major kidney or liver issues, neuromuscular disorders, severe lung disease requiring oxygen, or be on certain medications like calcium channel blockers.

Inclusion Criteria

I have a heart condition involving the heart muscle or scarring.

You have a permanent pacemaker or implantable cardioverter defibrillator.

I have a heart condition involving the heart muscle or scarring.

Exclusion Criteria

Pregnant or nursing

I am currently taking calcium channel blockers.

I have been intubated or am currently on a breathing machine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time intravenous administration of Dantrolene or placebo to study the effect on cardiac electrophysiology and hemodynamics

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including various physiological measurements

2-4 hours post-procedure

1 visit (in-person)

Treatment Details

Interventions

• Dantrolene/Ryanodex
• Placebo

Trial Overview The study tests if Dantrolene can affect cardiac electrophysiology and reduce the inducibility of ventricular arrhythmias in patients with heart structure problems. It's a randomized trial where half the participants will receive Dantrolene while the other half will get a placebo.

Participant Groups

Group I: Dantrolene/Ryanodex Experimental Treatment 1 Intervention

Dantrolene/Ryanodex; intravenous administration of dantrolene; 1 mg/ kg IV over 3 minute, one time dose

Group II: Placebo Placebo Group 1 Intervention

controlled placebo of saline administered Intravenous; 1 mg/kg IV over 3 minutes, one time dose

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Findings from Research

A comprehensive database of 396,985 drug-related cardiac adverse effects (AEs) linked to 1,632 approved drugs was created, revealing significant clusters of AEs affecting heart function, such as arrhythmias and heart failure.

The study identified that cardiac AEs are highly correlated with drugs targeting cardiovascular functions and specific mechanisms of action, including interactions with various receptors like alpha- and beta-adrenergic receptors, which may help predict and understand these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediction of drug-related cardiac adverse effects in humans--A: creation of a database of effects and identification of factors affecting their occurrence. Matthews, EJ., Frid, AA.[2013]

Cardiac safety pharmacology is crucial for assessing the risk of potentially lethal heart-related side effects from new drugs, particularly focusing on the risk of torsades de pointes (TdP) linked to changes in the QT interval on ECG.

The current paradigm for cardiac safety assessment, guided by ICH S7A and S7B, emphasizes the use of advanced non-clinical models and methods, including in vitro assays and biomarkers, to predict and monitor cardiac risks associated with new chemical entities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysics and Molecular Biology of Cardiac Ion Channels for the Safety Pharmacologist. Pugsley, MK., Curtis, MJ., Hayes, ES.[2015]

The review highlights the importance of assessing the cardiac safety profile of antiemetic drugs, particularly 5HT3 receptor antagonists, used in cancer patients to prevent chemotherapy-induced nausea and vomiting.

Most antiemetic drugs were approved before the implementation of ICHE14 guidelines, meaning their cardiotoxicity was primarily evaluated through post-marketing surveillance rather than controlled studies, indicating a need for ongoing monitoring of their cardiac effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiotoxicity of antiemetic drugs in oncology: An overview of the current state of the art. Barni, S., Petrelli, F., Cabiddu, M.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Evaluation of ventricular arrhythmias in early clinical pharmacology trials and potential consequences for later development. [2010]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Prediction of drug-related cardiac adverse effects in humans--A: creation of a database of effects and identification of factors affecting their occurrence. [2013]

3. Germany pubmed.ncbi.nlm.nih.gov

Biophysics and Molecular Biology of Cardiac Ion Channels for the Safety Pharmacologist. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Adverse reactions to antiarrhythmic drugs during therapy for ventricular arrhythmias. [2016]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Cardiotoxicity of antiemetic drugs in oncology: An overview of the current state of the art. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of dantrolene sodium in rodent models of cardiac arrhythmia. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Ryanodine receptor inhibition with acute dantrolene treatment reduces arrhythmia susceptibility in human hearts. [2023]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Antiarrhythmic potential of drugs targeting the cardiac ryanodine receptor Ca2+ release channel: case study of dantrolene. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Dantrolene prevents arrhythmogenic Ca2+ release in heart failure. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Dantrolene reduces CaMKIIδC-mediated atrial arrhythmias. [2021]