Phase 2
N=60
12-Week Study Evaluating the Efficacy, Safety, and Tolerability of Adjunctive Infliximab for Bipolar I/II Depression
Bipolar Depression
Bottom Line
View on ClinicalTrials.gov: NCT02363738 ↗Enrolled (actual)
60
Serious AEs
5.0%
Results posted
Jul 2021
Primary outcome: Primary: Baseline and Week 12 Montgomery-Asberg Depression Rating Scale (MADRS) Scores — 29.61; 27.79; 18.64; 16.06 units on a scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Infliximab (Drug); Saline (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University Health Network, Toronto
- Primary completion
- Apr 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Baseline and Week 12 Montgomery-Asberg Depression Rating Scale (MADRS) Scores |
29.61; 27.79; 18.64; 16.06 | — |
| PRIMARY Baseline and Week 6 Montgomery-Asberg Depression Rating Scale (MADRS) Scores |
29.61; 27.79; 19.44; 20.94 | — |
| SECONDARY Changes in Brain N-acetylaspartate Levels |
5.67; 5.65; 5.71; 5.81 | — |
| SECONDARY Changes in Anhedonia |
34.04; 34.8; 37.17; 40.79 | — |
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).
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 = 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
- 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
Data sourced from ClinicalTrials.gov (NCT02363738). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.