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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
One treatment condition in an open-label study design: subcutaneous injection of tocilizumab 162 mg at weeks 0, 2, 4, 6, and 8.
Icahn School of Medicine at Mount Sinai
New York, New York, United States
RECRUITINGChange in ventral stratal activation during reward processing (fMRI)
Change in ventral stratal activation (brain response) during reward processing (fMRI)
Time frame: at week 0 and week 10
Change in Snaith-Hamilton Pleasure Scale (SHAPS)
Changes in the following scales from baseline to end of treatment: Snaith-Hamilton Pleasure Scale (SHAPS): SHAPS total score ranges from 14 to 56, with higher scores indicating greater anhedonia.
Time frame: at week 0 and week 12
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
Changes in the following scales from baseline to end of treatment: Montgomery-Asberg Depression Rating Scale (MADRS): MADRS total score ranges from 0 to 60, with higher scores indicating greater depression severity.
Time frame: at week 0 and week 12
Change in Temporal Experience of Pleasure Scale (TEPS)
Changes in the following scales from baseline to end of treatment: Temporal Experience of Pleasure Scale (TEPS): TEPS total score ranges from 25 to 120, with lower scores indicating greater anhedonia severity.
Time frame: at week 0 and week 12
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