Comparing Immune System Suppression to Medication for Unexplained Heart Function and Irregular Heartbeat (IMMUNE VT)

December 3, 2024 updated by: Roderick Tung

Immunosuppression Versus Medical Therapy for UN-explained Low Ejection Fraction and VT

Ventricular tachycardia (VT, a potentially fatal condition where the ventricle of the heart beats rapidly) superimposed on non-ischemic cardiomyopathy (NICM, a disease of heart with broad etiologies except coronary artery disease). This disease has been associated with inflammation in the heart.

The purpose of this study is to assess the benefit of immunosuppressive therapy to suppress the VT, improve heart function, avoid invasive intervention and hospitalization. Positron Emission Tomography (PET) imaging shows inflammation in the heart. After enrollment, baseline tests (including physical exams, blood tests, genetic test, electrocardiography, echocardiography) will be done. Next, will be an 8-week medication regimen which contains either immunosuppressive drugs or standard GDMT without immunosuppressant medication. Some of the examinations will be repeated during the study to evaluate the treatment response and monitor any adverse events.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

Ventricular arrhythmia (VT) is a well-established consequence in patients with non-ischemic cardiomyopathy (NICM). NICM is a broad category that includes a wide spectrum of causes, which may include: bacterial, viral toxin mediated and immune mediated and "unexplained" when coronary disease has been excluded. The pathophysiology of NICM is not well understood but inflammatory responses with macrophage recruitment during remodeling have been described. On the other hand, an infectious trigger i.e. myocarditis may be the inciting event for the development of cardiomyopathy. A previous study by Tung et al showed that nearly 50% of patients with unexplained cardiomyopathy and ventricular arrhythmias presented ongoing focal myocardial inflammation on PET. To date, targeting inflammation as a substrate in order to reduce burden of ventricular tachycardia has not been investigated in randomized prospective fashion.

The TIMIC trial was one of the few randomized studies to examine long-term benefit of immunosuppressive therapies in patients with virus-negative NICM. A moderate improvement in Left Ventricular Ejection Fraction (LVEF) over 6 months after initiation of immunosuppressive therapy was demonstrated in this study but current guidelines do not routinely recommend anti-inflammatory therapies for NICM. While considered to be gold standard, endomyocardial biopsy can often times be incorrect due to sampling error and typically is not performed multiple times in patient with chronic non-ischemic cardiomyopathy. Fasting Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is an emerging imaging modality to identify and monitor abnormal metabolic patterns of the myocardium. By exploiting the metabolic demand of inflammatory tissue with macrophage recruitment, PET imaging is emerging as the preferred modality to diagnose and measure response to therapy for patients with myocarditis and sarcoidosis. A recent study by Kandolin et al in Finland showed that the incidence of cardiac sarcoidosis has increased by 20-fold over the past two decades.

FDG-PET may reveal inflammation as a central pathophysiologic mechanism in a significant proportion of patients with unexplained cardiomyopathy and VT. Potential innovative insights from the trial will be to identify the underlying pathogenesis of idiopathic cardiomyopathy and assess whether immunosuppression changes the clinical course of patients with identified arrhythmogenic cardiomyopathy. Aside from guideline-direct medical therapy (GDMT), antiarrhythmic agents, and catheter ablation, there are no disease-specific therapies for patients with VT and NICM. Prospective studies that evaluate the incidence of occult inflammation and clinical response to anti-inflammatory and immunosuppressive therapy have not been performed to date and are warranted for the emerging NICM population referred for advanced heart failure and arrhythmia management.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Banner - University Medical Center, Phoenix campus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18 years of age, all races, all gender
  • LV systolic function < 50%
  • Optimized GDMT Per physicians' discretion (SOC treatment)
  • No evidence of ischemic cardiomyopathy
  • No evidence of obstructive coronary disease
  • Viral panel negative
  • NYHA class II, III and ambulatory class IV heart failure
  • History of VA (documentation of Sustained VT last more than 30 seconds)
  • Heart inflammation confirmed by PET scan
  • Steroid use within 12 months prior to of date of consent

Exclusion Criteria:

  • Life expectancy less than 24 months
  • Pregnancy
  • Contra indications or intolerance of prednisone or any excipients in the formulation
  • Hypothalamic-pituitary-adrenal axis suppression, Cushing's syndrome, active infection, glaucoma or any other pathology where corticosteroids are not recommended.
  • Any patient with HIV, low white blood cells, and chronic infection (active fungal, TB, Valley fever)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Immunosuppression
Prednisone 40mg x 8weeks + GDMT
Drug: Prednisone 40mg
Prednisone 40mg x 8weeks
No Intervention: Standard of Care
GDMT alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Burden of ventricular arrhythmias
Time Frame: 12 months (8 weeks and 6 months)
Documented sustained monomorphic ventricular tachycardia >30 seconds or any appropriate defibrillator therapy (shock or antitachycardia pacing).
12 months (8 weeks and 6 months)
Change in left ventricular ejection fraction (LVEF)
Time Frame: 12 months (8 weeks and 6 months)
Left ventricular ejection fraction measured with Simpson method with echocardiography.
12 months (8 weeks and 6 months)
Change in QRS duration
Time Frame: 12 months (8 weeks and 6 months)
QRS duration (milliseconds) measured with a 12-lead ECG.
12 months (8 weeks and 6 months)
Change in FDG (18F-fluorodeoxyglucose) uptake
Time Frame: 12 months
Change in FDG uptake compared to initial uptake assessed with 18F-fluorodeoxyglucose PET (FDG-PET). Myocardial FDG uptake will be reported as non, focal or diffuse and/or isolated with focal pattern.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiovascular hospitalization
Time Frame: 6 months and 12 months.
Patient hospitalization (yes/no) due to a cardiovascular reason. Cardiovascular hospitalization is defined as a hospital admission after the randomized procedure for heart failure, treatment associated complication, or arrhythmia-related causes during the follow-up period.
6 months and 12 months.
Need for catheter ablation
Time Frame: 6 months and 12 months.
Need for catheter ablation (yes/no) due to ventricular arrhythmias.
6 months and 12 months.
NYHA functional class
Time Frame: 6 months and 12 months
New York Heart Association functional class I, II, III or IV.
6 months and 12 months
Survival
Time Frame: 6 months and 12 months
Freedom from all-cause mortality and cardiac transplant.
6 months and 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Medication adverse events
Time Frame: 6 months and 12 months
Medication related adverse events: steroid-induced diabetes, infection, weight gain, osteopenia, or psychosis.
6 months and 12 months
System related adverse events
Time Frame: 6 months and 12 months.
System related adverse events: worsening LVEF, high frequency of ventricular tachycardia seen on monitoring, or hospitalizations related to either.
6 months and 12 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Roderick Tung

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2024

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

October 1, 2027

Study Registration Dates

First Submitted

October 8, 2024

First Submitted That Met QC Criteria

October 8, 2024

First Posted (Actual)

October 10, 2024

Study Record Updates

Last Update Posted (Estimated)

December 5, 2024

Last Update Submitted That Met QC Criteria

December 3, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00003729

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After the study is completed, the de-identified, archived data will be stored within REDCap, for use by other researchers including those outside of the study, but only within the University of Arizona. The consent for the study includes information that de-identified data may be used for future unspecified research.

IPD Sharing Time Frame

After completion of study and stored for future unspecified research. Only de-identified data will be made available.

IPD Sharing Access Criteria

A request for access to the de-identified data will be made and access will only be granted to those with permission from the PI.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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