Major Depressive DisorderPhase 2NCT07493317
Neutralizing Interleukin (IL)-6
A Phase 2 study testing Tocilizumab in people with Major Depressive Disorder, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Mar 2026to 6 Feb 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Mackenzie Hargrove, 332-243-7052, mackenzie.brown@mssm.edu
Matthew Dobbs, 332-243-7055, matthew.dobbs@mssm.edu
About this study
Official title: Neutralizing Interleukin (IL)-6 Signaling to Reverse Immune Related Anhedonia in Patients With Major Depressive Disorder
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.
Read the 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
- Being tested
- Tocilizumab
- Keywords
- Depression, Monoclonal antibody, Healthy Volunteer, Tocilizumab, Interleukin-6, Anhedonia, fMRI
- Medical subject headings
- Depressive Disorder, Major, Depression, Anhedonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
One treatment condition in an open-label study design: subcutaneous injection of tocilizumab 162 mg at weeks 0, 2, 4, 6, and 8.
| Study group | Role | What they receive |
|---|---|---|
| Participants with MDD | Experimental | MDD participants will receive 5 doses of tocilizumab 162 mg administered via subcutaneous injection every 2 weeks over an 8-week period. Receives: Drug: Tocilizumab |
| Healthy Control | No intervention | Healthy controls will serve as a baseline comparison group for neuroimaging and biomarker analyses only. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ventral stratal activation during reward processing (fMRI)
Change in ventral stratal activation (brain response) during reward processing (fMRI)
Measured: at week 0 and week 10
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: at week 0 and week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2026
- Study start26 Mar 2026
- Primary completion6 Feb 2031 (estimated)
- Study completion6 Feb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James Murrough, Icahn School of Medicine at Mount Sinai
- Investigators
- James Murrough, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07493317
- Sponsor's protocol ID
- STUDY-25-01000
- Status last verified
- Apr 2026
- First submitted
- 20 Mar 2026
- Last updated
- 29 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared due to privacy concerns related to sensitive psychiatric and neuroimaging data.
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neutralizing Interleukin (IL)-6 Signaling to Reverse Immune Related Anhedonia in Patients With Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT07493317
- Acronym / sponsor ID
- STUDY-25-01000
- Conditions
- Major Depressive Disorder
- Keywords
- Depression, Monoclonal antibody, Healthy Volunteer, Tocilizumab, Interleukin-6, Anhedonia, fMRI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- 26 Mar 2026 (actual)
- Primary completion
- 6 Feb 2031 (estimated)
- Study completion
- 6 Feb 2031 (estimated)
- First posted
- 25 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Participants with MDD | Experimental | Drug: TocilizumabMDD participants will receive 5 doses of tocilizumab 162 mg administered via subcutaneous injection every 2 weeks over an 8-week period. |
| Healthy Control | No intervention | –Healthy controls will serve as a baseline comparison group for neuroimaging and biomarker analyses only. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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;
Key exclusion criteria (27 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TocilizumabOne treatment condition in an open-label study design: subcutaneous injection of tocilizumab 162 mg at weeks 0, 2, 4, 6, and 8. | Drug | Participants with MDD |
Primary outcome
Change in ventral stratal activation during reward processing (fMRI)
Time frame: at week 0 and week 10
Change in ventral stratal activation (brain response) during reward processing (fMRI)
3 secondary outcomes
Change in Snaith-Hamilton Pleasure Scale (SHAPS)
Time frame: at week 0 and week 12
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: at week 0 and week 12
Change in Temporal Experience of Pleasure Scale (TEPS)
Time frame: at week 0 and week 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be shared due to privacy concerns related to sensitive psychiatric and neuroimaging data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
James Murrough principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tocilizumab in people with Major Depressive Disorder, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alexia Lizzano (3322437059, alexia.lizzano@mssm.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in ventral stratal activation during reward processing (fMRI) (time frame: at week 0 and week 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2026.