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Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis (MAGiC-ART)

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ClinicalTrials.gov Identifier: NCT04017936
Recruitment Status : Recruiting
First Posted : July 12, 2019
Last Update Posted : October 18, 2019
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Virginia Commonwealth University

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.


Condition or disease Intervention/treatment Phase
Cardiac Sarcoidosis Drug: Anakinra Drug: Placebos Phase 2

Detailed Description:

Researchers will perform a double-blind randomized placebo-controlled 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).

Specific Aim #1: To determine the effects of anakinra on systemic inflammation

Specific Aim #2: To determine the effects of anakinra on cardiac inflammation and fibrosis (scar tissue)


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blind, randomized, placebo-controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : May 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sarcoidosis
Drug Information available for: Anakinra

Arm Intervention/treatment
Experimental: Anakinra
100 mg/0.67 mL daily subcutaneous injection for 4 weeks
Drug: Anakinra
Active Treatment

Placebo Comparator: Placebo
0.67 mL daily subcutaneous injection for 4 weeks
Drug: Placebos
Placebo




Primary Outcome Measures :
  1. Change in inflammation marker [ Time Frame: Baseline to 28 days ]
    Change in c-reactive protein in participant plasma samples


Secondary Outcome Measures :
  1. Change in cardiac functioning [ Time Frame: Baseline to 28 ]
    Change in heart function as measured by tracer activity using positron emission tomography (PET) scans

  2. Change in cardiac damage [ Time Frame: Baseline to 28 ]
    Change in late gadolinium enhancement evident on magnetic resonance imaging (MRI) scan

  3. Number of serious cardiac events [ Time Frame: 28 days ]
    Sum of hospitalizations and deaths due to cardiac causes



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA (all 3 criteria need to be met)

  • Clinical diagnosis of cardiac sarcoidosis according to the Heart Rhythm Society based on one of the 2 diagnosis pathways:

    1. Histological diagnosis from myocardial tissue - cardiac sarcoidosis is diagnosed in the presence of non-caseating granuloma on histologic examination of myocardial tissue with no alternative cause identified (including negative stain for microorganisms - as applicable);
    2. Clinical diagnosis from invasive and/or non-invasive studies - it is probable that there is cardiac sarcoidosis if there is (a) histological diagnosis of extracardiac sarcoidosis and (b) one or more of the following: steroid +/- immunosuppressant responsive cardiomyopathy or heart block; unexplained reduction in LVEF (<40%); unexplained sustained (spontaneous or induced) ventricular tachycardia; Mobitz type II 2nd degree or 3rd degree AV block; patchy uptake on dedicated cardiac PET (in a pattern consistent with cardiac sarcoidosis); late gadolinium enhancement on cardiac magnetic resonance (in a pattern consistent with cardiac sarcoidosis); positive gallium uptake (in a pattern consistent with cardiac sarcoidosis) and (c) other causes for the cardiac manifestation(s) have been reasonable excluded.
  • Cardiac fluoro-deoxyglucose uptake on recent PET (performed within the prior month).
  • CRP high-sensitivity assay >2 mg/l.

Exclusion Criteria:

Age<21 years;

  • Pregnancy;
  • Inability to obtain consent from patient or legally authorized representative;
  • Contraindications to treatment with Anakinra (Kineret)(i.e. prior allergic reaction to the drug or to E. coli derived products or severe allergy to latex);
  • Severe anemia (Hgb>8 g/dl - due to the need of more frequent blood sampling with this study).
  • Acute or chronic active infections (not including treated/cured HCV with negative viral load).
  • Acute or chronic inflammatory disease or immunosuppressive therapies (including oral corticosteroids at a dose of prednisone equivalent of 0.5 mg/kg/day but not including inhaled or low dose oral corticosteroids or non-steroidal anti-inflammatory drugs).
  • Active acute or chronic psychiatric illness that in the opinion of the investigator may prevent from complying with study instructions;
  • Patients may be on stable doses of steroids or steroid-sparing agents including methotrexate but not other biologic agents including TNF-blockers.
  • Limited English Proficiency that in the opinion of the investigator may prevent participants from safely completing the study procedures.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04017936


Contacts
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Contact: Jordana Kron, MD 804-828-7565 jordana.kron@vcuhealth.org
Contact: Antonio Abbate, ME, PhD 804-828-0513 aabbate@vcu.edu

Locations
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United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Jennifer Jordan, PhD    804-628-6239    Jennifer.Jordan@vcuhealth.org   
Sponsors and Collaborators
Virginia Commonwealth University
American Heart Association
Investigators
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Principal Investigator: Jordana Kron, MD Virginia Commonwealth University

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Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT04017936     History of Changes
Other Study ID Numbers: HM20015843
First Posted: July 12, 2019    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: Yes
Additional relevant MeSH terms:
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Sarcoidosis
Lymphoproliferative Disorders
Lymphatic Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents