Neutralizing Interleukin (IL)-6
Neutralizing Interleukin (IL)-6 Signaling to Reverse Immune Related Anhedonia in Patients With Major Depressive Disorder
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years to 70 Years
- Sex
- All sexes
- Healthy volunteers
- Accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Time periods mentioned: 8 weeks
- Procedures mentioned: MRI scans
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "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."
- "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."
- "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)."
- "The primary objective is to assess change in neural reward circuitry function, measured by ventral striatal activation during reward processing tasks using functional MRI."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests whether tocilizumab shots under the skin are safe and practical for adults with major depression and signs of increased immune activity. Over 8 weeks, researchers will also study whether the drug changes how the brain responds to rewards. Healthy adults will have blood tests and brain MRI scans but will not get the drug.
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.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Everyone: Be 18–70 years old. Any gender may join.
- Everyone: Give written consent, be able to follow study rules, and safely have an MRI scan.
- Depression group: Have major depressive disorder and be having a depression episode now.
- Depression group: Have at least 500 monocytes, a type of immune cell, per microliter of blood.
- Depression group: Score at least 20 on the SHAPS, a survey about your ability to feel pleasure.
- Depression group: If taking an antidepressant, have taken the same dose for at least 4 weeks before treatment.
- Depression group: Follow birth control rules through 6 months after the last dose. Women who can become pregnant must use accepted birth control or avoid sex. Men with a female partner who can become pregnant, is pregnant, or is breastfeeding must use barrier birth control. Female partners must also use highly effective birth control starting at least one cycle before treatment.
- Healthy group: Have no current or past mental health disorder.
Who can't join
- Depression group: Another main mental health diagnosis, except allowed anxiety disorders or post-traumatic stress disorder; a history of psychosis or bipolar disorder; or a major disorder affecting memory and thinking.
- Depression group: Moderate or severe substance use disorder in the past 6 months, except nicotine use. Either group: A positive urine test for illegal drugs.
- Depression group: Serious risk of harming yourself or others, a suicide attempt in the past 2 years, or a score above 2 on the C-SSRS suicide-thought scale in the past month.
- Depression group: Unsafe or unable to have an MRI, important exam or blood test problems, serious or unstable illness, or another condition that could harm safety or study results. Healthy group: Any current or unstable medical illness.
- Depression group: Active or untreated infection, including active or untreated inactive tuberculosis (TB), a positive TB screening test, known HIV, or active hepatitis B or C.
- Depression group: Current or recent use of biologic drugs or medicines that weaken the immune system. Healthy group: Use of these medicines. Both groups may use anti-inflammatory pain medicines as needed.
- Depression group: Allergy to tocilizumab or its ingredients, or a live vaccine within 30 days before the first dose or planned during the study.
- Depression group: Pregnant, breastfeeding, or unwilling to follow birth control rules through 6 months after the last dose. Healthy group: Pregnant at the starting study tests.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
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 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. Exclusion Criteria: 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). * Positive urine toxicology screen for illicit substances at screening. * Pregnancy at the time of baseline assessments (e.g., MRI).
Study sites (1)
NY
- Icahn School of Medicine at Mount Sinai · New York, NY 10029Mackenzie Hargrove · Study contact · 332-243-7052 · mackenzie.brown@mssm.eduMatthew Dobbs · Study contact · 332-243-7055 · matthew.dobbs@mssm.eduJames Murrough · Principal investigatorMore trials in New York