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Bipolar DepressionPhase 2NCT02363738

12-Week Study Evaluating the Efficacy, Safety, and Tolerability of Adjunctive Infliximab for Bipolar I/II Depression

A Phase 2 study testing Infliximab and Saline in people with Bipolar Depression, run by University Health Network, Toronto at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Studies show the presence of immuno-inflammatory disturbances in individuals with Bipolar Disorders (BD). Increased levels of circulating proteins known as cytokines that promote inflammation have been consistently reported in individuals with bipolar disorders. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Bipolar Depression
What is being tested?
Infliximab and Saline
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
2 sitesin 2 countries
Study dates
Sep 2015to Apr 2017
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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Fifth edition of Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria for major depressive episode as part of bipolar I/II disorder and are able to provide written informed consent
  • HAMD-17 score >= 20
  • Young Mania Rating Scale score < 12
  • Previous failed trial (i.e., inefficacy) of quetiapine and one other Canadian Network for Mood and Anxiety Treatments (CANMAT) BD guideline/FDA approved first line treatment for the depressive phase of BD during the index episode and/or during a prior episode
  • Currently prescribed conventional mood stabilizer or atypical antipsychotic agent
  • Received conventional treatment for bipolar depression for a minimum of 4 weeks prior to randomization
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  • Females of childbearing potential must test negative for pregnancy and must be using adequate birth control measures throughout the study and must continue such precautions for 6 months after receiving the last study drug administration.
  • Participants will also need to meet one of the following inflammatory indicators:
  • Central Obesity (ethnicity-specific waist circumference - see table below for specific values) OR BMI ≥30 kg/m2.
  • AND
  • Raised triglycerides: ≥1.7 mmol/L (150 mg/dL) or specific treatment for this lipid abnormality OR
  • Reduced HDL-cholesterol: <1.03 mmol/L (40 mg/dL) in males; <1.29 mmol/L (50 mg/dL) in females or specific treatment for this lipid abnormality OR
  • Raised Blood Pressure: Raised blood pressure Systolic: ≥130 mm Hg or diastolic: ≥85 mm Hg or treatment of previously diagnosed hypertension.
  • Diabetes: 8-hour fasting plasma glucose ≥ 7.0 mmol/L or Hb-A1C test ≥ 6.5% (as per the 2013 CDA diagnostic criteria) or previously diagnosed type 1 or 2 diabetes (current prescription medication for diabetes acceptable of diagnosis). Participants with child onset of diabetes will be excluded.
  • Inflammatory bowel disorder (Ulcerative Colitis, Crohn's disease).
  • Rheumatological disorders (rheumatoid arthiristis); Psoriasis.
  • Smoking cigarettes (daily - minimum of ½ pack).
  • High sensitivity C-reactive protein level of ≥5 mg/L via blood test at screening

Who cannot join

  • Another concurrent psychiatric disorder that requires primary clinical attention
  • History of schizophrenia
  • Active psychotic symptoms
  • Substance abuse and/or dependence within past 6 months
  • Electroconvulsive therapy in the past 6 months
  • Actively suicidal or evaluated as being a suicide risk [HAMD-17 suicide item >= 3 or Montogomery Asberg Depression Rating Scale (MADRS) suicide item >= 4, or according to clinical judgement using the C-SSRS]
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  • Clinically significant unstable medical illness
  • Severe infections such as sepsis, abscess, tuberculosis and opportunistic infections
  • Viral hepatitis B
  • History of Hepatitis C ( documented or suspected)
  • Any autoimmune disorder
  • History of tuberculosis or a high risk of tuberculosis exposure
  • Human Immunodeficiency Virus confirmed by laboratory testing
  • Active fungal infection
  • History of recurrent viral or bacterial infections
  • Received within 3 months prior to screening or are expected to receive any live viral vaccine or live bacterial vaccinations during the trial or up to 3 months after the last administration of study agent
  • C. difficile infection within the past 4 months
  • History of lymphoproliferative disease
  • History of cancer, excluding basal cell or squamous cell carcinoma of the skin (fully excised with no recurrence)
  • Unstable cardiovascular, endocrinological, hematological, hepatic, renal or neurological disease determined by physical examination and laboratory testing
  • Concomitant diagnosis or any history of congestive heart failure
  • Concomitant treatment with non-steroidal and steroidal anti-inflammatory medications or other biologics
  • Current or past exposure to anti-TNF biologics
  • Previous immediate hypersensitivity response, including anaphylaxis to an immunoglobulin product (plasma-derived or recombinant, e.g. monoclonal antibody)
  • Known allergies, hypersensitivity or intolerance to infliximab or its excipients
  • Known allergy to murine proteins or other chimeric proteins
  • Currently on or have used any investigational drug within 30 days prior to screening, or within 5 half-lives of the investigational agent
  • Females who are pregnant or breastfeeding

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • VA Palo Alto Health Care System

    Palo Alto, California, 94304

Other trials in United States

Canada1 site

  • Toronto Western Hospital

    Toronto, Ontario, M5T2S8

Other trials in Canada

About this study

Official title: A Multisite, Fixed Dose, Randomized, Double-Blind, Placebo-Controlled 12-Week Study Evaluating the Efficacy, Safety, and Tolerability of Adjunctive Infliximab for the Treatment of Bipolar I/II Depression

Studies show the presence of immuno-inflammatory disturbances in individuals with Bipolar Disorders (BD). Increased levels of circulating proteins known as cytokines that promote inflammation have been consistently reported in individuals with bipolar disorders. A particular cytokine referred to as Tumor Necrosis Factor (TNF)-alpha is among those cytokines that have been consistently identified across depressive, manic, and euthymic periods. Disturbances in inflammation however, are not seen in all individual with bipolar disorder. Those individuals with signs of inflammation also often present with higher prevalence of medical disorders that are also associated with inflammation. Those individuals with significant signs of inflammation may respond to anti-inflammatory treatments. In this study, individuals with bipolar depression who exhibit signs of high inflammation will be enrolled and treated with either an anti-inflammatory biologic known as infliximab or placebo (saline).

Being tested
Infliximab, Saline
Keywords
Bipolar Disorder, Bipolar Depression, Inflammation, Bipolar
Medical subject headings
Bipolar Disorder, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • InfliximabDrug

    Also called Remicade

    Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation. Infliximab will be prescribed adjunctively to a conventional mood stabilizer or atypical antipsychotic agent.

  • SalineOther

    Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency and will be administered adjunctively to conventional mood stabilizer or atypical antipsychotic agent.

Study groups in NCT02363738
Study groupRoleWhat they receive
InfliximabExperimentalIntravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation
Receives: Drug: Infliximab
Saline (Placebo)Placebo comparatorIntravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency.
Receives: Other: Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Baseline and Week 12 Montgomery-Asberg Depression Rating Scale (MADRS) Scores

    Baseline and Week 12 Montgomery-Asberg Depression Rating Scale scores are provided, with the range of possible values on the scale from 0 to 60. The higher the score, the worse the overall depressive symptoms.

    Measured: Up to 12 weeks

  2. Baseline and Week 6 Montgomery-Asberg Depression Rating Scale (MADRS) Scores

    Baseline and Week 6 Montgomery-Asberg Depression Rating Scale (MADRS) scores, where the range of possible values on the scale is from 0 to 60. The higher the score, the worse the overall depressive symptoms.

    Measured: Up to 6 weeks

Secondary outcomes (2)

  1. Changes in Brain N-acetylaspartate Levels

    Changes in prefrontal metabolites concentration of N-acetylaspartate, using proton-magnetic resonance spectroscopy (1H-MRS), adjusted for age, sex, baseline values and % gray matter in the spectroscopic region of interest.

    Measured: Baseline to Week 12

  2. Changes in Anhedonia

    Change in the Snaith-Hamilton Pleasure Scale (SHAPS) total score. Total score range of 14 to 56, with greater scores indicative of greater hedonic capacity.

    Measured: Baseline to 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Feb 2015 (estimated)
  2. Study startSep 2015
  3. Primary completionApr 2017
  4. Study completionApr 2017

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02363738
Sponsor's protocol ID
Infliximab-BD
Status last verified
Jun 2021
First submitted
5 Jan 2015
Last updated
28 Jul 2021
Data monitoring committee
No

Publications

  • Lee Y, Mansur RB, Brietzke E, Carmona NE, Subramaniapillai M, Pan Z, Shekotikhina M, Rosenblat JD, Suppes T, Cosgrove VE, Kramer NE, McIntyre RS. Efficacy of adjunctive infliximab vs. placebo in the treatment of anhedonia in bipolar I/II depression. Brain Behav Immun. 2020 Aug;88:631-639. doi: 10.1016/j.bbi.2020.04.063. Epub 2020 May 4.

    PubMed 32380271

  • McIntyre RS, Subramaniapillai M, Lee Y, Pan Z, Carmona NE, Shekotikhina M, Rosenblat JD, Brietzke E, Soczynska JK, Cosgrove VE, Miller S, Fischer EG, Kramer NE, Dunlap K, Suppes T, Mansur RB. Efficacy of Adjunctive Infliximab vs Placebo in the Treatment of Adults With Bipolar I/II Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2019 Aug 1;76(8):783-790. doi: 10.1001/jamapsychiatry.2019.0779.

    PubMed 31066887

  • Lee Y, Subramaniapillai M, Brietzke E, Mansur RB, Ho RC, Yim SJ, McIntyre RS. Anti-cytokine agents for anhedonia: targeting inflammation and the immune system to treat dimensional disturbances in depression. Ther Adv Psychopharmacol. 2018 Nov 19;8(12):337-348. doi: 10.1177/2045125318791944. eCollection 2018 Dec.

    PubMed 30524702

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Infliximab and Saline in people with Bipolar Depression, run by University Health Network, Toronto at 2 sites in 2 countries.

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 18 inclusion and 28 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: finished, as of the sponsor's last update on 28 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Canada. 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. Some participants in this study may receive a placebo. 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 28 Jul 2021). 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?

Baseline and Week 12 Montgomery-Asberg Depression Rating Scale (MADRS) Scores (time frame: Up to 12 weeks). The study lists 2 primary outcomes in all. 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 NCT02363738, 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 28 Jul 2021.

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