Evaluating the Efficacy of Adjunctive Minocycline for the Treatment of Bipolar Depression
Recruitment status was: Recruiting
Bipolar I Depression
Bipolar II Depression
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot, Open-label, 8-Week Study Evaluating the Efficacy, Safety, and Tolerability of Adjunctive Minocycline for the Treatment of Bipolar Depression|
- Change from baseline to week 8 on the Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: Baseline, Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]The MADRS assesses depressive symptoms
- Change from baseline to week 8 on the Hamilton Depression Rating Scale 17-item (HAMD-17) [ Time Frame: Baseline, Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]The HAMD-17 assesses depressive symptoms
- Change from baseline to week 8 on the Somatic Symptom Inventory (SSI) [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]
- Change from baseline to week 8 on the Clinical Global Impression (CGI) Rating Scale [ Time Frame: Baseline, Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]
- Change from baseline to week 8 in the in neurocognitive function [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]California Verbal Learning Test- second edition (CVLT-II), Process Dissociation Task, Trail Making Test A and B, Verbal Fluency- Delis-Kaplan Executive Function System (D-KEFS,) Digit Symbol Substitution, Cognitive Failures Questionnaire
- Monitoring of Side-effects from baseline to week 8 with the Toronto Side Effect Scale (TSES) [ Time Frame: Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: Yes ]
- Monitoring of suicide severity from baseline to week 8 with the Columbia Suicide Severity Rating Scale (C-SSRS). [ Time Frame: Baseline, Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: Yes ]
- Change from baseline to week 8 in concentrations of pro-and anti-inflammatory cytokines (i.e. TNFα, IL-1β, IL-2, IL-6, IL8, IFNγ, IL-4, IL-5, IL-10) [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||August 2013|
|Estimated Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Minocycline (100 mg bid) will be administered as an adjunctive agent to conventional Health Canada-approved, or first-line CANMAT bipolar guideline-recommended, agents for bipolar disorder.
Other Name: Minocin
Bipolar disorder (BD) is associated with a high-rate of non-recovery, recurrence, and inter-episodic dysfunction. Depressive symptoms and episodes dominate the longitudinal course of BD and differentially account for overall illness burden. During the past decade, substantial developments have been made in the pharmacological and psychosocial treatment of bipolar mania and maintenance, with relatively few treatments proven efficacious for bipolar depression. The absence of an explanatory disease model in bipolar disorder has limited the development and evaluation of genuinely novel agents for bipolar disorder.
Several lines of evidence implicate the inflammatory system as consequential and causative to mood disorder. Bipolar disorder is marked by alterations in inflammatory cytokines (e.g. TNF-alpha, IL-6). Moreover, pro-inflammatory activation in both healthy and medically ill individuals is associated with disturbances in affective, cognitive, and somatic function.
The clinical use of cytokine-based therapy has been demonstrated to induce and/or intensify affective symptomatology in non-psychiatric medical patients. Conventional pharmacological treatments (e.g. lithium) for bipolar disorder affects the production of pro-inflammatory cytokines as well as their gene expression. The encompassing aim of the study herein is to develop a novel treatment for bipolar depression based on a model of disease pathophysiology. Minocycline is a semisynthetic second-generation tetracycline, which exerts anti-inflammatory effects that are distinct from its antimicrobial properties.
Minocycline is a potent inhibitor of microglial activation and decreases expression of pro-inflammatory cytokines, chemokines and their receptors and suppresses the activity of matrix metalloproteinases. Minocycline has been shown to exert antidepressant-like properties in preclinical studies. Rats treated with minocycline monotherapy as well as combination treatment with an antidepressant (desipramine) exhibited significantly improved performance on the forced swim test. Adjunctive minocycline has been shown to be efficacious for the treatment of schizophrenia in a double-blind, randomized, placebo-controlled study. Subjects receiving minocycline exhibited a significant improvement in negative symptoms as well as global improvement as measured with the Clinical Global Impression (CGI). Significant improvement was also noted on measures of executive function, including executive function composite score, spatial recognition memory, cognitive planning, and intradimensional/extradimensional set shifting.
A total of 40 individuals between the ages of 18 and 65 meeting DSM-IV-TR criteria for a current major depressive episode as part of bipolar I or II disorder will be enrolled into an 8-week, open-label study with adjunctive minocycline (100 mg every 12 hours).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01403662
|University Health Network|
|Toronto, Ontario, Canada, M5T 2S8|
|Principal Investigator:||Roger S McIntyre, MD, FRCPC||University Health Network, Toronto|