Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis (NCT04017936) | Clinical Trial Compass
CompletedPhase 2
Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis
United States17 participantsStarted 2020-10-23
Plain-language 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.
Who can participate
Age range21 Years
SexALL
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Inclusion criteria
✓. 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);
✓. 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.
✓. Histological diagnosis group (those with positive myocardial biopsy findings) Cardiac sarcoidosis is diagnosed histologically when endomyocardial biopsy or surgical specimens demonstrate non-caseating epithelioid granulomas.
✓. Clinical diagnosis group (those with negative myocardial biopsy findings or those not undergoing myocardial biopsy)
✓. When epithelioid granulomas are found in organs other than the heart and clinical findings strongly suggestive of the above-mentioned cardiac involvement are present (Table 1); or
✓. When the patient shows clinical findings strongly suggestive of pulmonary or ophthalmic sarcoidosis; at least 2 of the 5 characteristic laboratory findings of a sarcoidosis (Table 2); and clinical findings strongly suggest the above-mentioned cardiac involvement (Table 1)
✓. 2 or more of the 5 major criteria (a)-(e) are satisfied.
✓. 1 of the 5 major criteria (a)-(e) and 2 or more of the 3 minor criteria (f)-(h) are satisfied.
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 (excluding stable \[\>1 month\] oral corticosteroids at a dose of prednisone less than 0.5 mg/kg/day or methotrexate).
✕. Active acute or chronic psychiatric illness that in the opinion of the investigator may prevent from complying with study instructions;