Tocilizumab Augmentation in Treatment-Refractory Major Depressive Disorder

Study Overview
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Brief Summary
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This proposed study sets out to examine the antidepressant effects of tocilizumab among patients with treatment-refractory major depression.

Detailed Description
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As the understanding of the complex relationship between pro-inflammatory cytokines (specifically interleukin-6 [IL-6]) and depression symptoms becomes clearer, clinical trials to evaluate effective and novel treatments are needed. 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 notion that inflammatory cytokines may play a role in a sub-type of depression, this study will recruit patients with treatment refractory major depressive disorder, for whom established depression treatments have not been effective. In conducting this trial, the investigators seek to examine the potential role of tocilizumab as an augmentation agent, with the hypothesis that it could reduce depression symptomatology in patients with major depression who have not experienced symptom reduction through more traditional antidepressant therapies.

Official Title
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Tocilizumab Augmentation in Treatment-Refractory Major Depressive Disorder: An Open-Label Trial

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current diagnosis of major depressive episode Hamilton Depression Rating Scale (HDRS) score of >20 In treatment for depression for a minimum of 8 weeks Exclusion criteria: Active drug or alcohol disorder in the last three months History of psychosis, mania or hypomania Acute suicide or homicide risk History of liver disease including HCV and HBV HIV History of heart disease or a heart attack Active or latent tuberculosis, a history of a positive tuberculosis test, or having received the Bacillus Calmette-Guérin (BCG) vaccine Epilepsy or a history of seizures Abnormal thyroid-stimulating hormone (TSH <0.4 or >5.0mlU/L) Abnormal liver function tests on screening (ALT>50 U/L or AST>50 U/L) Low absolute neutrophil count (ANC) on screening (<4000/mm3 Abnormal white blood cell count (<4,500 or > 10,000mcL) Low platelet count on screening (<150,000/mm3 Patients with an active or recent infection, for example cellulitis, bacteremia, pneumonia, and pyelonephritis. Recent exposure to uncommon infections (e.g. histoplasmosis, blastomycosis, coccidiomycosis) through recent travel to the Ohio and Mississippi River Valleys and the Southwest Pregnant women, breastfeeding women or women of child-bearing age not using contraception History of or current autoimmune disease, including multiple sclerosis and inflammatory bowel disease Diagnosis of chronic fatigue syndrome Temperature greater than 100.3F at the screening visit or any subsequent visits Dyslipidemia Currently taking oral steroids Currently taking statins Chronic aspirin or NSAID takers Currently taking any immunomodulating medications Inability to consent due to cognitive impairment

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tocilizumab<br>Tocilizumab 162 mg sc q2weeks x 4 doses | Drug: Tocilizumab<br>* Subcutaneous tocilizumab<br>* Other names: Actemra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change on Hamilton Depression Rating Scale (HDRS) | Absolute change on Hamilton Depression Rating Scale (HDRS) score | Baseline to 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Achieving Remission (HDRS Score < 7) | Proportion of Subjects with an HDRS score < 7 | 8 Weeks | 
| Proportion of Subjects Achieving Response (HDRS Score Decreased >50% From Baseline) | Proportion of Subjects with an HDRS score decreased >50% from baseline | 8 Weeks |