Sarcoidosis is a heterogeneous disorder of unknown etiology whose signature lesions are granulomatous inflammatory infiltrates in involved tissues. Tissue commonly affected are lungs, skin, eyes, lymph nodes and the heart. In this latter case, cardiac sarcoidosis (CS) can lead to atrioventricular (AV) blocks, ventricular arrhythmias, heart failure (HF) and sudden cardiac death. Similar to other involved organs, cardiac disease generally progresses from areas of focal inflammation to scar. However, the natural history of CS is not well characterized complicating an immediate and definitive diagnosis. The management of CS often requires multidisciplinary care teams and is challenged by data limited to small observational studies and from the high likelihood of side effects of most of the treatments currently used (eg: corticosteroids, methotrexate and TNF-alfa inhibitors).
Interleukin-1 (IL-1) is the prototypical pro-inflammatory cytokine, also referred to as master regulator of the inflammatory response, involved in virtually every acute process. There is evidence that IL-1 plays a role in mouse model of sarcoidosis and human pulmonary lesions as the presence of the inflammasome in granulomas of the heart of patients with cardiac sarcoidosis, providing additional support for a role of IL-1 in the pathogenesis of CS. However, IL-1 blockade has never been evaluated as a potential therapeutic agent for cardiac sarcoidosis.
In the current study, researchers aim to evaluate the safety and efficacy of IL-1 blockade with anakinra (IL-1 receptor antagonist) in patients with cardiac sarcoidosis.
Condition or disease | Intervention/treatment | Phase |
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Cardiac Sarcoidosis | Drug: Anakinra | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 28 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis |
Actual Study Start Date : | October 23, 2020 |
Estimated Primary Completion Date : | August 2023 |
Estimated Study Completion Date : | December 2023 |
Arm | Intervention/treatment |
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Experimental: Anakinra
100 mg/0.67 mL daily subcutaneous injection for 4 weeks
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Drug: Anakinra
Active Treatment
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No Intervention: Standard of Care
Continue standard of care treatment
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Ages Eligible for Study: | 21 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
INCLUSION CRITERIA (all 3 criteria need to be met)
Heart Rhythm Society Diagnostic Criteria based on 2 diagnostic pathways:
Japanese Cardiac Sarcoidosis Diagnostic Criteria:
The patient is clinically diagnosed as having sarcoidosis:
TABLE 1. Clinical findings defining cardiac involvement Cardiac findings should be assess based on the major criteria and the minor criteria. Clinical findings that satisfy the following 1) or 2) strongly suggest the presence of cardiac involvement.
1. Major criteria
Table 2. Characteristic laboratory findings of sarcoidosis 6. Bilateral hilar lymphadenopathy 7. High serum angiotensin-converting (ACE) activity or elevated serum lysozyme levels 8. High serum soluble interleukin-2 receptor (sIL-2R) levels 9. Significant tracer accumulation in 67Ga citrate scintigraphy or 18F-FDG PET 10. A high percentage of lymphocytes with a CD4CD8 ration of >3.5 in BAL fluid. 11.
Diagnostic guidelines for isolated cardiac sarcoidosis based on New CS Guidelines in Japan Prerequisite
EXCLUSION CRITERIA (any of the following criteria would result in exclusion)
Contact: Jordana Kron, MD | 804-828-7565 | jordana.kron@vcuhealth.org | |
Contact: Antonio Abbate, ME, PhD | 804-828-0513 | aabbate@vcu.edu |
United States, Michigan | |
University of Michigan Sarcoidosis Clinic | Recruiting |
Ann Arbor, Michigan, United States, 48109 | |
Contact: Thomas Crawford, MD 734-936-6858 thomcraw@med.umich.edu | |
United States, Virginia | |
Virginia Commonwealth University | Recruiting |
Richmond, Virginia, United States, 23298 | |
Contact: Virginia Mihalick, MS 804-628-3981 virginia.mihalick@vcuhealth.org |
Principal Investigator: | Jordana Kron, MD | Virginia Commonwealth University |
Tracking Information | |||||||||
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First Submitted Date ICMJE | July 9, 2019 | ||||||||
First Posted Date ICMJE | July 12, 2019 | ||||||||
Last Update Posted Date | November 9, 2020 | ||||||||
Actual Study Start Date ICMJE | October 23, 2020 | ||||||||
Estimated Primary Completion Date | August 2023 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Change in inflammation marker [ Time Frame: Baseline to 28 days ] Change in c-reactive protein in participant plasma samples
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Original Primary Outcome Measures ICMJE |
Change in c-reactive protein [ Time Frame: Baseline to 28 days ] Change in c-reactive protein in participant plasma samples
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Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis | ||||||||
Official Title ICMJE | Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis | ||||||||
Brief Summary |
Sarcoidosis is a heterogeneous disorder of unknown etiology whose signature lesions are granulomatous inflammatory infiltrates in involved tissues. Tissue commonly affected are lungs, skin, eyes, lymph nodes and the heart. In this latter case, cardiac sarcoidosis (CS) can lead to atrioventricular (AV) blocks, ventricular arrhythmias, heart failure (HF) and sudden cardiac death. Similar to other involved organs, cardiac disease generally progresses from areas of focal inflammation to scar. However, the natural history of CS is not well characterized complicating an immediate and definitive diagnosis. The management of CS often requires multidisciplinary care teams and is challenged by data limited to small observational studies and from the high likelihood of side effects of most of the treatments currently used (eg: corticosteroids, methotrexate and TNF-alfa inhibitors). Interleukin-1 (IL-1) is the prototypical pro-inflammatory cytokine, also referred to as master regulator of the inflammatory response, involved in virtually every acute process. There is evidence that IL-1 plays a role in mouse model of sarcoidosis and human pulmonary lesions as the presence of the inflammasome in granulomas of the heart of patients with cardiac sarcoidosis, providing additional support for a role of IL-1 in the pathogenesis of CS. However, IL-1 blockade has never been evaluated as a potential therapeutic agent for cardiac sarcoidosis. In the current study, researchers aim to evaluate the safety and efficacy of IL-1 blockade with anakinra (IL-1 receptor antagonist) in patients with cardiac sarcoidosis. |
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Detailed Description | Researchers will perform an open label randomized clinical trial of anakinra (recombinant IL-1 receptor antagonist, Kineret, SOBI, Sweden) given for 4 weeks in 28 patients with cardiac sarcoidosis (defined using Heart Rhythm Society diagnostic criteria). | ||||||||
Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Cardiac Sarcoidosis | ||||||||
Intervention ICMJE | Drug: Anakinra
Active Treatment
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
28 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | December 2023 | ||||||||
Estimated Primary Completion Date | August 2023 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
INCLUSION CRITERIA (all 3 criteria need to be met)
The patient is clinically diagnosed as having sarcoidosis:
TABLE 1. Clinical findings defining cardiac involvement Cardiac findings should be assess based on the major criteria and the minor criteria. Clinical findings that satisfy the following 1) or 2) strongly suggest the presence of cardiac involvement.
1. Major criteria
Table 2. Characteristic laboratory findings of sarcoidosis 6. Bilateral hilar lymphadenopathy 7. High serum angiotensin-converting (ACE) activity or elevated serum lysozyme levels 8. High serum soluble interleukin-2 receptor (sIL-2R) levels 9. Significant tracer accumulation in 67Ga citrate scintigraphy or 18F-FDG PET 10. A high percentage of lymphocytes with a CD4CD8 ration of >3.5 in BAL fluid. 11.
EXCLUSION CRITERIA (any of the following criteria would result in exclusion)
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Sex/Gender ICMJE |
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Ages ICMJE | 21 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT04017936 | ||||||||
Other Study ID Numbers ICMJE | HM20015843 1R21TR003103 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Virginia Commonwealth University | ||||||||
Study Sponsor ICMJE | Virginia Commonwealth University | ||||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Virginia Commonwealth University | ||||||||
Verification Date | November 2020 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |