NCT02363738

Brief 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. 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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Sep 2015

Geographic Reach
2 countries

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 5, 2015

Completed
1 month until next milestone

First Posted

Study publicly available on registry

February 16, 2015

Completed
7 months until next milestone

Study Start

First participant enrolled

September 1, 2015

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2017

Completed
4.3 years until next milestone

Results Posted

Study results publicly available

July 28, 2021

Completed
Last Updated

July 28, 2021

Status Verified

June 1, 2021

Enrollment Period

1.6 years

First QC Date

January 5, 2015

Results QC Date

June 14, 2021

Last Update Submit

July 7, 2021

Conditions

Bipolar Depression

Keywords

Bipolar DisorderBipolar DepressionInflammationBipolar

Outcome Measures

Primary Outcomes (2)

  • 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.

    Up to 12 weeks

  • 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.

    Up to 6 weeks

Secondary Outcomes (2)

  • Changes in Brain N-acetylaspartate Levels

    Baseline to Week 12

  • Changes in Anhedonia

    Baseline to 12 weeks

Study Arms (2)

Infliximab

EXPERIMENTAL

Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation

Drug: Infliximab

Saline (Placebo)

PLACEBO COMPARATOR

Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency.

Other: Saline

Interventions

InfliximabDRUG

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.

Also known as: Remicade
Infliximab
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.

Saline (Placebo)

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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).
  • +3 more criteria

You may not qualify if:

  • 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 \[HAMD-17 suicide item \>= 3 or Montogomery Asberg Depression Rating Scale (MADRS) suicide item \>= 4, or according to clinical judgement using the C-SSRS\]
  • 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
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

VA Palo Alto Health Care System

Palo Alto, California, 94304, United States

Location

Toronto Western Hospital

Toronto, Ontario, M5T2S8, Canada

Location

Related Publications (3)

  • 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.

    PMID: 32380271DERIVED

  • 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.

    PMID: 31066887DERIVED

  • 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.

    PMID: 30524702DERIVED

MeSH Terms

Conditions

Bipolar DisorderInflammation

Interventions

InfliximabSodium Chloride

Condition Hierarchy (Ancestors)

Bipolar and Related DisordersMood DisordersMental DisordersPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Results Point of Contact

Title
Dr. Roger McIntyre
Organization
University Health Network
roger.mcintyre@uhn.ca
416-603-5279

Study Officials

  • Roger S McIntyre, MD, FRCPC

    University of Toronto; University Health Network

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 5, 2015

First Posted

February 16, 2015

Study Start

September 1, 2015

Primary Completion

April 1, 2017

Study Completion

April 1, 2017

Last Updated

July 28, 2021

Results First Posted

July 28, 2021

Record last verified: 2021-06

Locations

US(1)CA(1)