NCT07493317

Neutralizing Interleukin (IL)-6

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Icahn School of Medicine at Mount Sinai · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

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.

Detailed description

This open-label, proof-of-concept interventional study is designed to evaluate the feasibility and safety of IL-6 receptor blockade using subcutaneous tocilizumab in adults with MDD and evidence of peripheral immune activation. Participants with MDD (N=20) meeting immune enrichment criteria (elevated monocyte count) will receive tocilizumab 162 mg administered subcutaneously every 2 weeks for 8 weeks (5 total doses). A comparison group of healthy volunteers (N=20) will undergo baseline neuroimaging and blood sampling but will not receive study drug. The primary objective is to assess change in neural reward circuitry function, measured by ventral striatal activation during reward processing tasks using functional MRI. Secondary objectives include evaluating changes in anhedonia and depressive symptoms using validated clinical scales (SHAPS, MADRS, TEPS), as well as changes in peripheral immune biomarkers.

Conditions

• Major Depressive Disorder

Interventions

Type	Name	Description
DRUG	Tocilizumab	One treatment condition in an open-label study design: subcutaneous injection of tocilizumab 162 mg at weeks 0, 2, 4, 6, and 8.

Timeline

• Start date: 2026-03-01
• Primary completion: 2031-02-06
• Completion: 2031-02-06
• First posted: 2026-03-25
• Last updated: 2026-03-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study