Neutralizing Interleukin (IL)-6

The proposed study aims to establish the feasibility and safety of subcutaneous tocilizumab, a monoclonal antibody (mAb) against interleukin (IL)-6 receptor, in adults with Major Depressive Disorder (MDD) and evidence of peripheral immune activation. IL-6 is a pro-inflammatory cytokine implicated in the pathophysiology of depression. The investigators hypothesize that neutralizing peripheral immune signaling via IL-6 receptor blockade with tocilizumab will improve neural and behavioral measures of reward processing. This is an open-label, proof-of concept, trial in which up to N=20 adults with MDD meeting a specific immune enrichment criterion will receive open-label tocilizumab over 8 weeks. A healthy control (HC) group (N=20) will undergo baseline neuroimaging and blood-based biomarker assessment without receiving the study drug to aid interpretation of findings. Blood-based immune markers and brain MRI scans (including task-based reward activation and resting-state functional connectivity) will be assessed at baseline for all participants and again post treatment for the MDD group.

NCT Number	NCT07493317
Lead Sponsor	Icahn School of Medicine at Mount Sinai
Conditions	Major Depressive Disorder
Enrollment	60 participants
Start Date	2026-03-26
Primary Completion	2031-02-06 (estimated)
Study Completion	2031-02-06 (estimated)
Updated on ClinicalTrials.gov	2026-04-29