Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis

Phase 2

Completed

• Conditions: Cardiac Sarcoidosis
• Interventions: Drug: Anakinra

• Registration Number: NCT04017936
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2019-07-09
• Study First Submitted QC: 2019-07-09
• Study First Posted: 2019-07-12
• Study Start: 2020-10-23
• Primary Completion: 2024-06-30
• Study Completion: 2024-06-30
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-09
• Last Update Posted: 2024-07-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anakinra	Anakinra	100 mg/0.67 mL daily subcutaneous injection for 4 weeks

Primary Outcome Measures

Name	Time	Method
Change in inflammation marker	Baseline to 28 days	Change in c-reactive protein in participant plasma samples

Secondary Outcome Measures

Name	Time	Method
Number of serious cardiac events	28 days	Sum of hospitalizations and deaths due to cardiac causes
Change in cardiac inflammation	Baseline to 28	Change in heart function as measured by tracer activity using positron emission tomography (PET) scans
Change in cardiac fibrosis	Baseline to 28	Change in late gadolinium enhancement evident on magnetic resonance imaging (MRI) scan

Trial Locations

Locations (2)

University of Michigan Sarcoidosis Clinic; 🇺🇸 Ann Arbor, Michigan, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States