Cell Free DNA Testing for Myocarditis

(cfDNA in CS Trial)

Overseen By Brenda Werner, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Nabeel Hamzeh

Must not be taking: Immunosuppressive therapy

Disqualifiers: Cardiac disease, Smoker, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore a new method for detecting heart inflammation in individuals with sarcoidosis, a condition that causes swelling in various organs. It employs a blood test to identify cell-free DNA, which can indicate tissue damage. The trial includes individuals with sarcoidosis, those who recently experienced a heart attack, and healthy participants. Participants should not smoke or have other heart diseases. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance early detection methods for heart inflammation.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on immunosuppressive therapy to participate.

What prior data suggests that this cell free DNA testing is safe for detecting myocarditis?

Research has shown that cell-free DNA (cfDNA) testing is generally easy for people to handle. Studies have used cfDNA testing as a noninvasive method to diagnose various conditions, including heart diseases like myocarditis. It involves a simple blood draw, a low-risk procedure for most individuals.

No major negative effects have been reported specifically from cfDNA testing. In fact, its use in other areas, such as cancer diagnosis and prenatal testing, suggests it is a safe tool. While researchers continue to study the procedure for myocarditis, the absence of serious side effects in other applications provides reassurance about its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses cell-free DNA testing to potentially identify myocarditis, a heart condition, without invasive procedures. Unlike traditional methods that often rely on biopsies or imaging, this approach only requires a simple blood draw, making it much less invasive and more accessible. This technique could lead to quicker and more accurate diagnosis, especially beneficial for conditions like myocarditis that can be challenging to detect early. By analyzing DNA fragments in the blood, it offers a novel way to monitor heart inflammation, potentially transforming how doctors diagnose and manage heart conditions.

What evidence suggests that this cell free DNA testing is effective for detecting active myocarditis?

Research has shown that cell-free DNA (cfDNA) testing could help detect heart problems, such as those in cardiac sarcoidosis. Studies have found that cfDNA is highly accurate, with an 87% chance of correctly identifying heart issues and a 96% chance of confirming when no issue exists. This trial will compare cfDNA testing across different groups: sarcoidosis patients with and without active myocarditis, healthy controls, and patients with acute ST elevation myocardial infarction (STEMI). The test identifies specific patterns that signal tissue damage, potentially spotting heart inflammation early in sarcoidosis. This approach could offer a new way to detect myocarditis early, aiding doctors in treatment decisions and possibly preventing further heart damage. ^{1 2 6 7 8}

Who Is on the Research Team?

Nabeel Hamzeh, MD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

This trial is for non-smokers with sarcoidosis diagnosed by ATS/ERS criteria, experiencing active myocarditis confirmed by cMRI or cFDG-PET. It includes those undergoing cardiac intervention for acute coronary syndrome (STEMI) and healthy controls without cardiovascular risks or known cardiac disease. Excluded are smokers, those on immunosuppressive therapy, hemodynamically unstable patients, and anyone with other known cardiac diseases.

Inclusion Criteria

I have no known heart diseases.

I am receiving treatment for a sudden heart problem.

I have been diagnosed with sarcoidosis but do not have active heart inflammation.

Exclusion Criteria

I had a severe heart attack and am currently unstable.

I have sarcoidosis without heart inflammation and I currently smoke.

I am currently a smoker and have had a recent heart attack.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial blood draw to measure cfDNA levels in all participant groups

1 day

1 visit (in-person)

Follow-up Assessment

Additional blood draws for sarcoidosis patients with active myocarditis and STEMI patients to monitor cfDNA levels

2 months

2 visits (in-person) for sarcoidosis with myocarditis, 2 visits (in-person) for STEMI

Follow-up

Participants are monitored for safety and effectiveness after the main assessments

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cell free DNA

Trial Overview The study tests the use of cell free DNA (cfDNA) as a diagnostic tool to identify granulomatous myocarditis in sarcoidosis patients. The goal is to find a specific biomarker that can guide treatment decisions and monitor response to therapy without the need for high-radiation imaging techniques like FDG-PET.

How Is the Trial Designed?

Group I: Sarcoidosis patients with evidence of active myocarditis Experimental Treatment 1 Intervention

Two blood draws 2 months apart.

Group II: Sarcoidosis patients without evidence of active myocarditis Active Control 1 Intervention

A single blood draw.

Group III: Acute ST elevation myocardial infarction (STEMI) Active Control 1 Intervention

Three blood draws, baseline, 6 hours and 24 hours.

Group IV: Healthy controls Placebo Group 1 Intervention

A single blood draw

Who Is Running the Clinical Trial?

Nabeel Hamzeh

Lead Sponsor

Trials

2

Recruited

140+

Published Research Related to This Trial

In a study of 30 patients with unexplained congestive heart failure, only 10% were found to have biopsy-proven myocarditis, indicating a low incidence of this condition in the sample.

The immunosuppressive treatment with prednisone and azathioprine in two patients showed clinical improvement, but their heart function did not improve as expected, suggesting that more research is needed to confirm the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocarditis and cardiomyopathy: diagnosis by endomyocardial biopsy. Arbustini, E., Gavazzi, A., Pucci, A., et al.[2014]

The Myocarditis Treatment Trial involved 66 patients receiving immunosuppressive therapy plus conventional treatment and 45 patients receiving only conventional treatment for 24 weeks, aiming to improve heart function in those with biopsy-confirmed myocarditis.

Results showed that the trial focused on measuring the improvement in left ventricular ejection fraction (LVEF) at week 28, with additional analyses planned for survival rates and immunological markers, highlighting the potential role of immunosuppressive therapy in treating myocarditis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Myocarditis Treatment Trial: design, methods and patients enrollment. Hahn, EA., Hartz, VL., Moon, TE., et al.[2019]

A systematic review of 8 randomized controlled trials involving 719 patients found that corticosteroid therapy did not significantly reduce mortality in patients with viral myocarditis.

However, patients receiving corticosteroids showed improved left ventricular ejection fraction post-treatment, indicating some potential benefit in heart function, though the overall evidence does not support routine corticosteroid use for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cochrane Corner: Corticosteroids for viral myocarditis. Caldeira, D., Lopes, LR., Vaz-Carneiro, A., et al.[2018]

In a study of 40 children under 21 diagnosed with myocarditis, treatment with high-dose steroids and IVIG resulted in a 92.5% transplant-free survival rate and significant recovery of heart function, with 70% regaining normal left ventricular function by 3 months.

The treatment was found to be safe, as there were no serious secondary bacterial infections reported after starting steroids, indicating that this combination therapy may be a viable option for managing acute myocarditis in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating Pediatric Myocarditis with High Dose Steroids and Immunoglobulin. Schauer, J., Newland, D., Hong, B., et al.[2023]

In a study of 11 patients with immune checkpoint inhibitor (ICI) myocarditis, 4 were treated with infliximab, suggesting it may be a safe option for those who do not respond to corticosteroids, despite its black box warning for heart failure.

While infliximab did not significantly shorten the time to troponin normalization compared to corticosteroids alone, all patients survived their initial hospital admission, indicating potential efficacy in managing this serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of corticosteroid refractory immune checkpoint inhibitor myocarditis with Infliximab: a case series. Zhang, RS., Padegimas, A., Murphy, KM., et al.[2021]

A new scoring system based on six clinical parameters can help predict the efficacy of steroid therapy in patients with active myocarditis, as demonstrated in a retrospective analysis of 21 patients.

In this study, non-steroid treatments were effective for patients with lower scores (-5 to -4), while steroid therapy showed better outcomes for those with higher scores (0 to +6), suggesting that the scoring system can guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new scoring system to predict the efficacy of steroid therapy for patients with active myocarditis--a retrospective study. Kodama, M., Okura, Y., Hirono, S., et al.[2019]

Scintigraphy using (99m)Tc-Anti-Granulocyte antibody was tested on 14 patients with confirmed myocarditis and successfully identified inflammation in 13 of them, suggesting it could be a valuable non-invasive diagnostic tool for myocarditis.

The study showed a strong agreement between scintigraphy results and myocardial biopsy findings, indicating that this imaging method may help in diagnosing myocarditis without the need for invasive procedures, although more research is needed to confirm its accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening for acute myocarditis--is scintigraphy with (99m)Tc-Anti-Granulocyte BW 250/183 an answer? Hubalewska, A., Dudek, D., Dubiel, J., et al.[2016]

In a study of 53 patients with idiopathic dysrhythmias, myocarditis was found in 36% of cases through histologic examination, highlighting its prevalence in this population.

Steroid therapy was effective in 77.8% of patients with biopsy-proven myocarditis, but only 29.4% in those with clinically suspected myocarditis but negative biopsies, indicating that steroid treatment may be more beneficial for confirmed cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of myocarditis in idiopathic dysrhythmias: role of endomyocardial biopsy and efficacy of steroid therapy. Thongtang, V., Chiathiraphan, S., Ratanarapee, S., et al.[2013]

In a study of 20 patients with myocarditis treated with prednisone and azathioprine, histologic improvement was observed in all patients, with 15 achieving complete resolution of inflammation, indicating the treatment's efficacy.

While overall left ventricular ejection fraction improved from 0.37 to 0.46, the direct impact of treatment on heart function recovery was unclear; however, some patients did show a correlation between histological improvement and enhanced ejection fraction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppressive treatment in myocarditis. Salvi, A., Di Lenarda, A., Dreas, L., et al.[2019]

In a study of 13 children with biopsy-proven myocarditis, steroid therapy (prednisone) led to significant clinical improvements, including normalization of ECG changes and heart function, with no significant side effects reported.

Repeat biopsies showed improvement in all patients, with six out of eight showing elimination of inflammatory infiltrate, suggesting that immunosuppressive therapy can effectively enhance recovery in pediatric myocarditis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppressive therapy in the management of acute myocarditis in children: a clinical trial. Chan, KY., Iwahara, M., Benson, LN., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03858777

NCT03858777 | Cell Free DNA in Cardiac Sarcoidosis Three blood draws, baseline, 6 hours and 24 hours. cfDNA level at baseline and 2 months for sarcoidosis with heart disease compared to cfDNA levels at baseline ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11511729/

Emerging Biomarkers in Cardiac Sarcoidosis and Other ... This review aims to summarize and highlight recent findings in the field of biomarkers for cardiac sarcoidosis and inflammatory cardiomyopathy.

3. withpower.com withpower.com/trial/phase-st-elevation-myocardial-infarction-4-2019-8d03f

Cell Free DNA Testing for Myocarditis (cfDNA in CS Trial) The cfDNA in CS medical study, being run by Nabeel Hamzeh, is evaluating whether Cell free DNA will have tolerable side effects & efficacy for patients with ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2352906723000775

Cell-free DNA as a potential biomarker for acute ... Diagnostic accuracy was determined using six studies (n = 804), which yielded a sensitivity of 87% (95%CI: 72%-95%) and specificity of 96% (95%CI: 92%-98%). The ...

5. jacc.org jacc.org/doi/10.1016/j.jacadv.2025.101745

Is it Time to Incorporate Genomic Data in the Routine ... Genetic testing is not part of the standard management of CS in 2024, and current diagnostic algorithms recommend genetic testing to exclude other diagnoses.

6. clinicalepigeneticsjournal.biomedcentral.com clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-025-01914-z

cfDNA methylation detection as potential liquid biopsy of ... cfDNA shows great potential as a noninvasive, early, and sensitive biomarker for reflecting disease severity and systemic injury in fulminant myocarditis.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2772487525001229

Circulating-free DNA: A promising tool for early detection of ... CfDNA levels provide valuable prognostic insights for MI outcomes. In ST-elevation myocardial infarction (STEMI), cfDNA concentrations are 5.93 times higher ...

8. myocarditisfoundation.org myocarditisfoundation.org/clinical-trials/

Clinical Trials Brief Summary This is a study to understand if taking VTX2735 is safe and effective in participants diagnosed with Recurrent Pericarditis (RP). Approximately 30 ...