RecruitingPhase 2NCT07493317

Neutralizing Interleukin (IL)-6

Neutralizing Interleukin (IL)-6 Signaling to Reverse Immune Related Anhedonia in Patients With Major Depressive Disorder

Sponsor

Icahn School of Medicine at Mount Sinai

Enrollment

60 participants

Start Date

Mar 26, 2026

Study Type

INTERVENTIONAL

Conditions

Major Depressive Disorder

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 70 Years

Plain Language Summary

Simplified for easier understanding

This open-label proof-of-concept study tests whether tocilizumab — a drug that blocks a protein called IL-6 involved in immune signaling and inflammation — can improve reward processing in the brain and reduce anhedonia (the inability to feel pleasure) in adults with major depressive disorder (MDD) who show signs of immune activation. The study targets a specific subtype of depression that may be driven by inflammation, which standard antidepressants often fail to address. Adults aged 18–70 with a current MDD episode, elevated monocyte counts (a blood marker of immune activation), and a high score on an anhedonia scale are eligible; people with active infections, certain other psychiatric diagnoses, or contraindications to MRI are excluded. Participation involves five subcutaneous injections of tocilizumab over 8 weeks, brain MRI scans, and blood draws at the start and end of treatment; a healthy control group completes imaging only at one time point. This summary was generated with AI assistance and is intended to help patients understand the study in plain language.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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