Neutralizing Interleukin (IL)-6 Signaling to Reverse Immune Related Anhedonia in Patients With Major Depressive Disorder
Icahn School of Medicine at Mount Sinai
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.
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…
Eligibility
- Age range
- 18–70 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: For MDD participants: * Written informed consent; * Ability to comply with the requirements of the study as determined by the PI; * Ages 18-70 years; * Any gender; * DSM-5 diagnosis of MDD in a current Major Depressive Episode; * Immune enrichment criterion: elevated monocyte count ≥ 500 cells/μL at screening; * If patient is on antidepressant medication, they must be on a stable dose for ≥4 weeks prior to treatment; * SHAPS score ≥20 * If female of childbearing potential, must agree to use of a medically accepted form of contraception, or else agree to abstinence until 6…
Interventions
- DrugTocilizumab
One treatment condition in an open-label study design: subcutaneous injection of tocilizumab 162 mg at weeks 0, 2, 4, 6, and 8.
Location
- Icahn School of Medicine at Mount SinaiNew York, New York