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Cell Free DNA in Cardiac Sarcoidosis (cfDNA in CS)

Primary Purpose

Sarcoidosis With Myocarditis, Sarcoidosis, Healthy

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
cell free DNA
Sponsored by
Nabeel Hamzeh
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Sarcoidosis With Myocarditis focused on measuring sarcoidosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers
  1. Sarcoidosis patients without evidence of active myocarditis:

    • Inclusion:

      • Diagnosis of sarcoidosis based on the ATS/ERS criteria.
      • Normal 12 lead ECG within the past one year.
      • Non-smoker.
      • No immunosuppressive therapy for at least one year.
    • Exclusion:

      • Known cardiac disease.
      • Active smoker.
      • On immunosuppressive therapy.
  2. Sarcoidosis patients with evidence of active myocarditis:

    • Inclusion:

      • Diagnosis of sarcoidosis based on the ATS/ERS criteria.
      • Evidence of active myocarditis based on recent cMRI or cFDG-PET.
      • Non-smoker.
    • Exclusion:

      • Known cardiac disease other than sarcoidosis.
      • Active smoker.
      • On immunosuppressive therapy.
  3. Acute ST elevation myocardial infarction (STEMI):

    • Inclusion:

      • Diagnosis STEMI based on 1mm ST elevation in 2 or more contiguous leads.
      • Symptom onset within 12 hours.
      • Undergoing cardiac intervention for acute coronary syndrome.
      • Able to consent for blood draw.
    • Exclusion:

      • Active smoker.
      • Hemodynamically unstable.
  4. Healthy controls:

    • Inclusion:

      • No known cardiac disease.
      • No known cardiovascular risk factors: hypertension, diabetes.
      • Non-smoker.

Sites / Locations

  • University of Iowa
  • University of IowaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Active Comparator

Placebo Comparator

Arm Label

Sarcoidosis patients without evidence of active myocarditis

Sarcoidosis patients with evidence of active myocarditis

Acute ST elevation myocardial infarction (STEMI)

Healthy controls

Arm Description

A single blood draw.

Two blood draws 2 months apart.

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

A single blood draw

Outcomes

Primary Outcome Measures

cfDNA level
cfDNA level

Secondary Outcome Measures

Full Information

First Posted
February 25, 2019
Last Updated
July 17, 2023
Sponsor
Nabeel Hamzeh
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1. Study Identification

Unique Protocol Identification Number
NCT03858777
Brief Title
Cell Free DNA in Cardiac Sarcoidosis
Acronym
cfDNA in CS
Official Title
Cardiomyocyte Specific Cell Free DNA as a Marker of Cardiac Sarcoidosis
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2019 (Actual)
Primary Completion Date
December 15, 2023 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Nabeel Hamzeh

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
Sarcoidosis is a multisystem granulomatous disease of unknown cause that can affect any organ in the body, including the heart. Granulomatous myocarditis can lead to ventricular dysfunction and ventricular arrhythmias causing significant morbidity and mortality. Immunosuppressive therapy (IST) has been shown to reverse active myocarditis and preserve left ventricular (LV) function and in some cases improve LV function. In addition, IST can suppress arrhythmias that develop due to active myocarditis and prevent the formation of scar. The potential role of cardiac biomarkers, including brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), and cardiac troponins, in detecting active myocarditis is limited and studies have been disappointing. At present, there are no biomarkers to detect active myocarditis and the use of advanced imaging modalities (FDG-PET) for assessing and monitoring active myocarditis is not feasible or practical and is associate with high radiation exposure. As such, a biomarker that is reflective of active myocarditis and that is cardiac specific will assist physicians in assessing the presence of active myocarditis to guide therapeutic decisions and to assess response to therapy which can limit further cardiac damage. Cell free DNA (cfDNA) are fragments of genomic DNA that are released into the circulation from dying or damaged cells. It is a powerful diagnostic tool in cancer, transplant rejection and fetal medicine especially when the genomic source differs from the host. A novel technique that relies on tissue unique CpG methylation patterns can identify the tissue source of cell free DNA in an individual reflecting potential tissue injury. We will be conducting a pilot study to explore the utility of this diagnostic tool to identify granulomatous myocarditis in patients with sarcoidosis.
Detailed Description
Sarcoidosis is a multisystem granulomatous disease of unknown cause that can affect any organ in the body, including the heart. Sarcoidosis results from an immune reaction to an environmental exposure to yet unknown antigen(s) in a genetically predisposed individual. Autopsy studies have suggested that cardiac involvement with sarcoidosis occurs in up to 25% of cases, although more than half of these cases are sub-clinical. Cardiac sarcoidosis (CS) CS can lead to life-threatening heart failure, heart block, or rhythm disturbance and accounts for 13-25% of all sarcoidosis deaths in the USA. Therefore, although respiratory failure from lung sarcoidosis is the most common cause of sarcoidosis-related death in the USA, sudden death from cardiac sarcoidosis is a major concern owing to its acute nature. CS can present in a multitude of ways. It can be the initial manifestation of sarcoidosis in an individual not known to have sarcoidosis (a cohort beyond the aims of this proposal), patients can present with cardiac symptoms which can include palpitations, near-syncope or syncopal episodes which require a complete workup for potential CS and patients can be asymptomatic which is a sizable cohort considering the discrepancy between the expected prevalence of CS (25-40%) and CS that is detected clinically (5%). Granulomatous myocarditis can lead to ventricular dysfunction and ventricular arrhythmias causing significant morbidity and mortality. Immunosuppressive therapy (IST) has been shown to reverse active myocarditis and preserve left ventricular (LV) function and in some cases improve LV function. In addition, IST can suppress arrhythmias that develop due to active myocarditis and prevent the formation of scar. Cardiac MRI (cMRI) and cardiac PET scans are currently used as complementary diagnostic tests for cardiac sarcoidosis, although with some limitations. Cardiac MRI with gadolinium has a sensitivity of 76-100% and specificity of 78-92% for the diagnosis of cardiac sarcoidosis, but its use is limited in patients with implantable cardiac devices. The presence of delayed enhancement on gadolinium-enhanced MRI is suggestive of scar tissue formation. 18FDG PET uses radioactive glucose to detect areas of active inflammation. The use of 18FDG PET as a marker of active granulomatous myocarditis should be interpreted carefully as several studies have shown the limitations of such protocols that force the myocardium to generate energy using free fatty acid metabolism exclusively. In addition, studies have also shown that the presumed pathological patterns, focal and focal on diffuse uptake, are also seen in healthy controls and patients with ischemic congestive heart failure who have undergone 18-FDG-PET12 and that a blood glucose level of >7.5mmol/L (>137mg/dl) at the time of the study results in absent or minimal myocardial FDG activity. The potential role of cardiac biomarkers, including brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), and cardiac troponins, in detecting active myocarditis is limited and studies have been disappointing. At present, there are no biomarkers to detect active myocarditis and the use of advanced imaging modalities (FDG-PET) for assessing and monitoring active myocarditis is not feasible or practical and is associate with high radiation exposure. As such, a biomarker that is reflective of active myocarditis and that is cardiac specific will assist physicians in assessing the presence of active myocarditis to guide therapeutic decisions and to assess response to therapy which can limit further cardiac damage. Cell free DNA (cfDNA) are fragments of genomic DNA that are released into the circulation from dying or damaged cells. It is a powerful diagnostic tool in cancer, transplant rejection and fetal medicine especially when the genomic source differs from the host. A novel technique that relies on tissue unique CpG methylation patterns can identify the tissue source of cell free DNA in an individual reflecting potential tissue injury. A recent paper utilized this technique to identify cardiac specific cfDNA in the bloodstream of patients with acute myocardial injury and sepsis reflecting cardiomyocyte injury/death. We will be conducting a pilot study to explore the utility of this diagnostic tool to identify granulomatous myocarditis in patients with sarcoidosis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoidosis With Myocarditis, Sarcoidosis, Healthy, ST Elevation Myocardial Infarction
Keywords
sarcoidosis

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sarcoidosis patients without evidence of active myocarditis
Arm Type
Active Comparator
Arm Description
A single blood draw.
Arm Title
Sarcoidosis patients with evidence of active myocarditis
Arm Type
Experimental
Arm Description
Two blood draws 2 months apart.
Arm Title
Acute ST elevation myocardial infarction (STEMI)
Arm Type
Active Comparator
Arm Description
Three blood draws, baseline, 6 hours and 24 hours.
Arm Title
Healthy controls
Arm Type
Placebo Comparator
Arm Description
A single blood draw
Intervention Type
Diagnostic Test
Intervention Name(s)
cell free DNA
Intervention Description
All groups will have blood draws and cfDNA measured
Primary Outcome Measure Information:
Title
cfDNA level
Description
cfDNA level
Time Frame
cfDNA level at baseline and 2 months for sarcoidosis with heart disease compared to cfDNA levels at baseline for healthy controls and sarcoidosis without cardiac disease and cfDNA levels at baseline, 6 and 24 hours for STEMI patients.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Sarcoidosis patients without evidence of active myocarditis: Inclusion: Diagnosis of sarcoidosis based on the ATS/ERS criteria. Normal 12 lead ECG within the past one year. Non-smoker. No immunosuppressive therapy for at least one year. Exclusion: Known cardiac disease. Active smoker. On immunosuppressive therapy. Sarcoidosis patients with evidence of active myocarditis: Inclusion: Diagnosis of sarcoidosis based on the ATS/ERS criteria. Evidence of active myocarditis based on recent cMRI or cFDG-PET. Non-smoker. Exclusion: Known cardiac disease other than sarcoidosis. Active smoker. On immunosuppressive therapy. Acute ST elevation myocardial infarction (STEMI): Inclusion: Diagnosis STEMI based on 1mm ST elevation in 2 or more contiguous leads. Symptom onset within 12 hours. Undergoing cardiac intervention for acute coronary syndrome. Able to consent for blood draw. Exclusion: Active smoker. Hemodynamically unstable. Healthy controls: Inclusion: No known cardiac disease. No known cardiovascular risk factors: hypertension, diabetes. Non-smoker.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Brenda Werner, RN
Phone
319-353-8862
Email
brenda-r-werner@uiowa.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nabeel Hamzeh, MD
Organizational Affiliation
University of Iowa
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brenda Werner, RN
Phone
319-353-8862
Email
brenda-r-werner@uiowa.edu
First Name & Middle Initial & Last Name & Degree
Nabeel Hamzeh, MD
Phone
319-356-8343
Email
nabeel-hamzeh@uiowa.edu
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brenda Werner, RN
Phone
319-353-8862
Email
brenda-r-werner@uiowa.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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Cell Free DNA in Cardiac Sarcoidosis

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