Tocilizumab for Depression

Overseen By Mackenzie Hargrove

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must be taking: Antidepressants

Must not be taking: Biologic therapies, Immunosuppressive agents

Disqualifiers: Schizophrenia, Bipolar, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 6

Duration: 8 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for Major Depressive Disorder (MDD) using a medication called tocilizumab. Tocilizumab targets interleukin-6, a protein linked to inflammation that may play a role in depression. The researchers aim to determine if this treatment can improve symptoms by reducing inflammation. Individuals diagnosed with MDD and a high monocyte count (a type of white blood cell) might be suitable for this trial. The study also includes a group of healthy volunteers to help compare results. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in depression treatment.

Is there any evidence suggesting that tocilizumab is likely to be safe for humans?

A previous study showed that patients with rheumatoid arthritis (RA) treated with tocilizumab had a lower chance of developing depression compared to those who did not receive the treatment. This suggests that tocilizumab might help improve mood. Another study found that tocilizumab was linked to noticeable improvements in depression symptoms for some patients.

However, the results are mixed. Some research found that tocilizumab could worsen depression symptoms in patients with other medical conditions. Despite this, in a larger group of patients, those taking tocilizumab reported better mental health and quality of life.

Overall, tocilizumab has been used for other conditions and is generally well-tolerated. However, like any medication, it can have side effects. It's important to talk to a healthcare provider about any concerns before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for MDD?

Most treatments for Major Depressive Disorder (MDD), like SSRIs or SNRIs, work by altering neurotransmitter levels in the brain. But tocilizumab works differently, targeting the immune system by neutralizing interleukin-6 (IL-6), an inflammatory molecule that may play a role in depression. Researchers are excited about tocilizumab because it offers a novel approach by addressing inflammation, which could be particularly beneficial for patients who don't respond well to traditional antidepressants. This new mechanism has the potential to change how we understand and treat depression, offering hope for more effective management of MDD symptoms.

What evidence suggests that tocilizumab might be an effective treatment for Major Depressive Disorder?

Research suggests that tocilizumab, a medication that blocks a specific protein involved in inflammation, may reduce the risk of depression. Studies with people who have rheumatoid arthritis show that those treated with tocilizumab were less likely to develop depression compared to those who were not. Another study found that depression symptoms decreased over time in people using this medication. Since this protein is linked to inflammation that can affect mood, blocking it with tocilizumab might help improve mental health. While these findings are promising, this trial will specifically evaluate the effects of tocilizumab on participants with major depressive disorder (MDD) to further understand its potential benefits. ^{1 3 6 7 8}

Who Is on the Research Team?

James Murrough

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

Inclusion Criteria

For MDD participants: Immune enrichment criterion: elevated monocyte count ≥ 500 cells/μL at screening

I am eligible regardless of my gender.

For MDD participants: 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

Exclusion Criteria

For MDD Participants: Moderate or severe substance use disorder within the past 6 months (excluding nicotine use disorder)

For MDD Participants: Any contraindication to MRI, including claustrophobia, retained metallic foreign bodies, magnetic implants or pacemakers, or inability to tolerate MRI procedures

I have a history of certain psychotic or bipolar disorders.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants with MDD receive 5 doses of tocilizumab 162 mg administered via subcutaneous injection every 2 weeks over an 8-week period

8 weeks

5 visits (in-person)

Follow-up

Participants are monitored for changes in neural reward circuitry function and depressive symptoms

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Tocilizumab

How Is the Trial Designed?

Group I: Participants with MDD Experimental Treatment 1 Intervention

MDD participants will receive 5 doses of tocilizumab 162 mg administered via subcutaneous injection every 2 weeks over an 8-week period.

Group II: Healthy Control Active Control 1 Intervention

Healthy controls will serve as a baseline comparison group for neuroimaging and biomarker analyses only.

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02660528

Study Details | NCT02660528 | Tocilizumab Augmentation ...

As there have been no published tocilizumab trials among patients with major depression, this pilot study will adopt a single-arm, open-label design. Due to the ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11460349/

Tocilizumab Reduces Depression Risk in Rheumatoid Arthritis ...

Tocilizumab monotherapy exhibited a promising beneficial effect on the risk of depression, indicated by the decreased risk in RA patients.

3.

tandfonline.com

tandfonline.com/doi/full/10.2147/PRBM.S482409

Tocilizumab Reduces Depression Risk in Rheumatoid ...

Tocilizumab monotherapy exhibited a promising beneficial effect on the risk of depression, indicated by the decreased risk in RA patients.

4.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/28/NCT02660528/Prot_SAP_000.pdf

Tocilizumab Augmentation in Treatment-Refractory Major ...

The results of this study also have potential to benefit larger clinical populations if it is identified that tocilizumab is an effective ...

5.

researchgate.net

researchgate.net/publication/384608426_Tocilizumab_Reduces_Depression_Risk_in_Rheumatoid_Arthritis_Patients_A_Systematic_Review_and_Meta-Analysis

(PDF) Tocilizumab Reduces Depression Risk in ...

Tocilizumab monotherapy exhibited a promising beneficial effect on the risk of depression, indicated by the decreased risk in RA patients ( ...

6.

nature.com

nature.com/articles/s41398-020-01164-y

The IL-6 antagonist tocilizumab is associated with worse ...

In that analysis, those treated with tocilizumab demonstrated statistically significant improvement in depressive symptoms; however, this meta- ...

7.

escholarship.org

escholarship.org/uc/item/6kc3r4rt

The IL-6 antagonist tocilizumab is associated with worse ...

Blockade of the IL-6 receptor with tocilizumab among medically ill patients resulted in significantly more-not less-depressive symptoms.

8.

clinexprheumatol.org

clinexprheumatol.org/article.asp?a=16554

Characterisation of depressive symptoms in rheumatoid ...

The aim of the current study was to assess whether tocilizumab was asso- ciated with changes in symptoms of depression during routine daily care ...