Major Depressive DisorderPhase 2NCT02660528
Tocilizumab Augmentation in Treatment-Refractory Major Depressive Disorder
A Phase 2 study testing Tocilizumab in people with Major Depressive Disorder, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
This proposed study sets out to examine the antidepressant effects of tocilizumab among patients with treatment-refractory major depression. Read more about this study
- Who is it for?
- Ages 30 to 60 years
- 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
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to Jun 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 30 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Current diagnosis of major depressive episode
- Hamilton Depression Rating Scale (HDRS) score of >20
- In treatment for depression for a minimum of 8 weeks
Who cannot join
- 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
Show all 25Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: Tocilizumab Augmentation in Treatment-Refractory Major Depressive Disorder: An Open-Label Trial
This proposed study sets out to examine the antidepressant effects of tocilizumab among patients with treatment-refractory major depression.
Read the 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.
- Conditions
- Major Depressive Disorder
- Being tested
- Tocilizumab
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called Actemra
Subcutaneous tocilizumab
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab | Experimental | Tocilizumab 162 mg sc q2weeks x 4 doses Receives: Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Change on Hamilton Depression Rating Scale (HDRS)
Absolute change on Hamilton Depression Rating Scale (HDRS) score
Measured: Baseline to 8 Weeks
Secondary outcomes (2)
Proportion of Subjects Achieving Remission (HDRS Score < 7)
Proportion of Subjects with an HDRS score < 7
Measured: 8 Weeks
Proportion of Subjects Achieving Response (HDRS Score Decreased >50% From Baseline)
Proportion of Subjects with an HDRS score decreased >50% from baseline
Measured: 8 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2016 (estimated)
- Study startApr 2016
- Primary completionJun 2020
- Study completionJun 2020
Why it stopped: Study staff change.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jessica Harder, Brigham and Women's Hospital
- Investigators
- Jessica Harder, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02660528
- Sponsor's protocol ID
- 2015P001263
- Status last verified
- Oct 2020
- First submitted
- 19 Jan 2016
- Last updated
- 20 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 23212583Al-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.
PubMed 25985379Fonseka 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.
PubMed 25585966
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tocilizumab Augmentation in Treatment-Refractory Major Depressive Disorder: An Open-Label Trial
- ClinicalTrials.gov ID
- NCT02660528
- Acronym / sponsor ID
- 2015P001263
- Conditions
- Major Depressive Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study staff change.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- Apr 2016 (actual)
- Primary completion
- Jun 2020 (actual)
- Study completion
- Jun 2020 (actual)
- First posted
- 21 Jan 2016 (estimated)
- Results
- Posted 20 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab | Experimental | Drug: TocilizumabTocilizumab 162 mg sc q2weeks x 4 doses |
Who may qualify
- Ages
- 30 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Current diagnosis of major depressive episode
- Hamilton Depression Rating Scale (HDRS) score of >20
- In treatment for depression for a minimum of 8 weeks
Key exclusion criteria (25 listed)
- 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
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 |
|---|---|---|
| TocilizumabAlso: ActemraSubcutaneous tocilizumab | Drug | Tocilizumab |
Primary outcome
Absolute Change on Hamilton Depression Rating Scale (HDRS)
Time frame: Baseline to 8 Weeks
Absolute change on Hamilton Depression Rating Scale (HDRS) score
2 secondary outcomes
Proportion of Subjects Achieving Remission (HDRS Score < 7)
Time frame: 8 Weeks
Proportion of Subjects Achieving Response (HDRS Score Decreased >50% From Baseline)
Time frame: 8 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23212583Sukoff 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.
- Background: PubMed 25985379Al-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.
- Background: PubMed 25585966Fonseka 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.
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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. This study is not recruiting at the moment.
Jessica Harder, MD principal investigator
Brigham and Women's Hospital
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 Brigham and Women's Hospital 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 3 inclusion and 25 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: stopped early, as of the sponsor's last update on 20 Oct 2020. 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?
Yes. Results are posted in the registry (first posted 20 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute Change on Hamilton Depression Rating Scale (HDRS) (time frame: Baseline to 8 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02660528, which also lists 3 linked publications.
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 20 Oct 2020.