Neutralizing Interleukin (IL)-6

Recruiting now · Phase 2

Conditions studied: Major Depressive Disorder

In brief

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.

Key facts

Study ID: NCT07493317
Run by: Icahn School of Medicine at Mount Sinai
People needed: 60
Starts: 2026-03-26
Expected to finish: 2031-02-06
Last updated by the study team: 2026-04-29

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: accepted.

You may qualify if…

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 months after the last dose of study drug;
Male patients, if heterosexually active with a partner who is female of childbearing potential, pregnant, or breastfeeding, must agree to barrier contraception for the treatment period and for at least 6 months after the last dose of the study drug. Female partners of male participants must use at least one form of highly effective contraception starting at least one cycle prior to male patient study drug initiation until 6 months after the last dose of study drug.
Meet all MRI safety criteria.
For Healthy Volunteers:
Written informed consent;
Ability to comply with the requirements of the study as determined by the PI;
Ages 18-70
Any gender;
No current or past DSM-5 psychiatric disorder;
Meet all MRI safety criteria.

You may not qualify if…

For MDD Participants
A primary DSM-5 psychiatric diagnosis other than MDD, with the exception of comorbid anxiety disorders (including agoraphobia, generalized anxiety disorder, social anxiety disorder, panic disorder) and post-traumatic stress disorder, which are permitted.
History of schizophrenia, schizoaffective disorder, other psychotic disorder, MDD with psychotic features, or bipolar I or II disorder.
Diagnosis of a major neurocognitive disorder.
Moderate or severe substance use disorder within the past 6 months (excluding nicotine use disorder).
Positive urine toxicology screen for illicit substances at screening.
Serious or imminent risk of self-harm or violence, as determined by the PI, including:
Suicide attempt within the past 2 years, or
C-SSRS ideation score >2 within the past month.
Any contraindication to MRI, including claustrophobia, retained metallic foreign bodies, magnetic implants or pacemakers, or inability to tolerate MRI procedures.
Clinically significant abnormalities on physical examination or laboratory testing.
Unstable or clinically significant medical illness, including but not limited to hepatic, renal, gastrointestinal, respiratory, cardiovascular (including ischemic heart disease), endocrine, neurologic (including history of severe head injury), immunologic, or hematologic conditions.
Evidence of active or untreated infection, including
Active tuberculosis (TB) or untreated latent TB
Positive QuantiFERON-TB Gold test at screening
Known HIV infection
Active Hepatitis B or Hepatitis C infection
Current or recent (within an appropriate washout period) use of biologic therapies or other immunosuppressive agents (PRN NSAIDs permitted).
Known hypersensitivity to tocilizumab or its excipients.
Receipt of a live or live-attenuated vaccine within 30 days prior to first dose, or planned receipt during the study period.
Pregnancy, breastfeeding, or unwillingness to use effective contraception during the study and for 6 months after the last dose.
Any condition that, in the opinion of the PI, would compromise participant safety or data integrity.
For Healthy Volunteers
Any current or unstable medical illness, including hepatic, renal, gastrointestinal, respiratory, cardiovascular (including ischemic heart disease), endocrine, neurologic (including history of severe head injury), immunologic, or hematologic disease.
Use of biologic therapies or immunosuppressive agents (PRN NSAIDs permitted).

Where it is running

Icahn School of Medicine at Mount Sinai — New York, New York, United States (enrolling)

Full record on ClinicalTrials.gov

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