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Tocilizumab Augmentation in Treatment-Refractory Major Depressive Disorder

Primary Purpose

Major Depressive Disorder

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tocilizumab
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder

Eligibility Criteria

30 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Brigham and Women's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tocilizumab

Arm Description

Tocilizumab 162 mg sc q2weeks x 4 doses

Outcomes

Primary Outcome Measures

Absolute Change on Hamilton Depression Rating Scale (HDRS)
Absolute change on Hamilton Depression Rating Scale (HDRS) score

Secondary Outcome Measures

Proportion of Subjects Achieving Remission (HDRS Score < 7)
Proportion of Subjects with an HDRS score < 7
Proportion of Subjects Achieving Response (HDRS Score Decreased >50% From Baseline)
Proportion of Subjects with an HDRS score decreased >50% from baseline

Full Information

First Posted
January 19, 2016
Last Updated
October 16, 2020
Sponsor
Brigham and Women's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02660528
Brief Title
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

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Terminated
Why Stopped
Study staff change.
Study Start Date
April 2016 (Actual)
Primary Completion Date
June 2020 (Actual)
Study Completion Date
June 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tocilizumab
Arm Type
Experimental
Arm Description
Tocilizumab 162 mg sc q2weeks x 4 doses
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
Actemra
Intervention Description
Subcutaneous tocilizumab
Primary Outcome Measure Information:
Title
Absolute Change on Hamilton Depression Rating Scale (HDRS)
Description
Absolute change on Hamilton Depression Rating Scale (HDRS) score
Time Frame
Baseline to 8 Weeks
Secondary Outcome Measure Information:
Title
Proportion of Subjects Achieving Remission (HDRS Score < 7)
Description
Proportion of Subjects with an HDRS score < 7
Time Frame
8 Weeks
Title
Proportion of Subjects Achieving Response (HDRS Score Decreased >50% From Baseline)
Description
Proportion of Subjects with an HDRS score decreased >50% from baseline
Time Frame
8 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jessica Harder, MD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23212583
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.
Results Reference
background
PubMed Identifier
25985379
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.
Results Reference
background
PubMed Identifier
25585966
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.
Results Reference
background

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Tocilizumab Augmentation in Treatment-Refractory Major Depressive Disorder

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