Comparing Immune System Suppression to Medication for Unexplained Heart Function and Irregular Heartbeat
NCT ID: NCT06635863
Last Updated: 2024-12-05
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
ENROLLING_BY_INVITATION
Clinical Phase
PHASE4
Total Enrollment
40 participants
Study Classification
INTERVENTIONAL
Study Start Date
2024-11-01
Study Completion Date
2027-10-31
Brief Summary
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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.
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.
Detailed Description
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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.
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.
Conditions
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Ventricular Arrythmia
Non-ischemic Cardiomyopathy
Arrhythmogenic Inflammatory Cardiomyopathy
Keywords
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immunosuppressive therapy
immunomodulatory
inflammation by FDG
guideline-direct medical therapy
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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Immunosuppression
Prednisone 40mg x 8weeks + GDMT
Group Type
EXPERIMENTAL
Prednisone 40mg
Intervention Type
DRUG
Prednisone 40mg x 8weeks
Standard of Care
GDMT alone
Group Type
NO_INTERVENTION
No interventions assigned to this group
Interventions
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Prednisone 40mg
Prednisone 40mg x 8weeks
Intervention Type
DRUG
Eligibility Criteria
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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
* 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)
* 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)
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Roderick Tung
OTHER
Sponsor Role
lead
Responsible Party
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Roderick Tung
Professor of Medicine; Chief, Division of Cardiology
Responsibility Role
SPONSOR_INVESTIGATOR
Locations
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Banner - University Medical Center, Phoenix campus
Phoenix, Arizona, United States
Site Status
Countries
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United States
References
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BACKGROUND
Belperio JA, Shaikh F, Abtin FG, Fishbein MC, Weigt SS, Saggar R, Lynch JP 3rd. Diagnosis and Treatment of Pulmonary Sarcoidosis: A Review. JAMA. 2022 Mar 1;327(9):856-867. doi: 10.1001/jama.2022.1570.
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Melani AS, Bigliazzi C, Cimmino FA, Bergantini L, Bargagli E. A Comprehensive Review of Sarcoidosis Treatment for Pulmonologists. Pulm Ther. 2021 Dec;7(2):325-344. doi: 10.1007/s41030-021-00160-x. Epub 2021 Jun 18.
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BACKGROUND
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BACKGROUND
Ishimaru S, Tsujino I, Takei T, Tsukamoto E, Sakaue S, Kamigaki M, Ito N, Ohira H, Ikeda D, Tamaki N, Nishimura M. Focal uptake on 18F-fluoro-2-deoxyglucose positron emission tomography images indicates cardiac involvement of sarcoidosis. Eur Heart J. 2005 Aug;26(15):1538-43. doi: 10.1093/eurheartj/ehi180. Epub 2005 Apr 4.
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BACKGROUND
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BACKGROUND
Kebed KY, Carter SV, Flatley E, Ward RP, Moss JD, Appelbaum DE, Singh A, Lang RM, Tung R, Patel AR. Prevalence of newly diagnosed sarcoidosis in patients with ventricular arrhythmias: a cardiac magnetic resonance and 18F-FDG cardiac PET study. Int J Cardiovasc Imaging. 2021 Apr;37(4):1361-1369. doi: 10.1007/s10554-020-02090-2. Epub 2020 Nov 22.
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BACKGROUND
Wicks EC, Menezes LJ, Barnes A, Mohiddin SA, Sekhri N, Porter JC, Booth HL, Garrett E, Patel RS, Pavlou M, Groves AM, Elliott PM. Diagnostic accuracy and prognostic value of simultaneous hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in cardiac sarcoidosis. Eur Heart J Cardiovasc Imaging. 2018 Jul 1;19(7):757-767. doi: 10.1093/ehjci/jex340.
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BACKGROUND
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Reference Type
BACKGROUND
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Other Identifiers
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STUDY00003729
Identifier Type: -
Identifier Source: org_study_id