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
Overview
- Phase
- Phase 2
- Intervention
- Infliximab
- Conditions
- Bipolar Depression
- Sponsor
- University Health Network, Toronto
- Enrollment
- 60
- Locations
- 2
- Primary Endpoint
- Baseline and Week 12 Montgomery-Asberg Depression Rating Scale (MADRS) Scores
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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/m
- •Raised triglycerides: ≥1.7 mmol/L (150 mg/dL) or specific treatment for this lipid abnormality OR
Exclusion Criteria
- •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)
Arms & Interventions
Infliximab
Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation
Intervention: Infliximab
Saline (Placebo)
Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency.
Intervention: Saline
Outcomes
Primary Outcomes
Baseline and Week 12 Montgomery-Asberg Depression Rating Scale (MADRS) Scores
Time Frame: Up to 12 weeks
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.
Baseline and Week 6 Montgomery-Asberg Depression Rating Scale (MADRS) Scores
Time Frame: Up to 6 weeks
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.
Secondary Outcomes
- Changes in Anhedonia(Baseline to 12 weeks)
- Changes in Brain N-acetylaspartate Levels(Baseline to Week 12)