Clinical trial NCT02660528: Tocilizumab Augmentation in Treatment-Refractory Major Depressive Disorder
Official title: Tocilizumab Augmentation in Treatment-Refractory Major Depressive Disorder: An Open-Label Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Major Depressive Disorder
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2016-01-21
Enrollment: 3
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Absolute Change on Hamilton Depression Rating Scale (HDRS)
timeFrame: Baseline to 8 Weeks
Secondary outcomes:
measure: Proportion of Subjects Achieving Remission (HDRS Score < 7)
timeFrame: 8 Weeks
measure: Proportion of Subjects Achieving Response (HDRS Score Decreased >50% From Baseline)
timeFrame: 8 Weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Jessica Harder, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sukoff Rizzo SJ, Neal SJ, Hughes ZA, Beyna M, Rosenzweig-Lipson S, Moss SJ, Brandon NJ. Evidence for sustained elevation of IL-6 in the CNS as a key contributor of depressive-like phenotypes. Transl Psychiatry. 2012 Dec 4;2(12):e199. doi: 10.1038/tp.2012.120.
citation: Al-Hakeim HK, Al-Rammahi DA, Al-Dujaili AH. IL-6, IL-18, sIL-2R, and TNFalpha proinflammatory markers in depression and schizophrenia patients who are free of overt inflammation. J Affect Disord. 2015 Aug 15;182:106-14. doi: 10.1016/j.jad.2015.04.044. Epub 2015 May 5.
citation: Fonseka TM, McIntyre RS, Soczynska JK, Kennedy SH. Novel investigational drugs targeting IL-6 signaling for the treatment of depression. Expert Opin Investig Drugs. 2015 Apr;24(4):459-75. doi: 10.1517/13543784.2014.998334. Epub 2015 Jan 14.