Evaluating the Efficacy of Adjunctive Minocycline for the Treatment of Bipolar Depression

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by University Health Network, Toronto.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01403662
First received: July 18, 2011
Last updated: July 25, 2011
Last verified: July 2011
  Purpose

Long-term studies have emphasized that depressive symptoms and episodes account for majority of the illness burden experienced by individuals with bipolar disorder (BD). Previous studies have shown that blood levels of proteins called pro-inflammatory cytokines are abnormal in individuals with bipolar depression. The investigators hypothesize that preventing the production or release of pro-inflammatory cytokines will result in improvement of depressive symptoms in individuals with bipolar depression. Minocycline is a medication that inhibits the activation of immune cells (i.e. microglia) in the brain and reduces the production of pro-inflammatory cytokines. Treatment with minocycline has been shown to have antidepressant-like effects in animal studies and improve symptoms of individuals with schizophrenia. In this study, minocycline (100 mg twice a day) will be administered for 8 weeks to determine if it is an efficacious antidepressant for individuals with bipolar depression.


Condition Intervention Phase
Bipolar Disorder
Bipolar Depression
Bipolar I Depression
Bipolar II Depression
Drug: Minocycline
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 40
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)
Arms Assigned Interventions
Experimental: Minocycline Drug: Minocycline
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

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of bipolar I or II disorder
  • Meets criteria for a current major depressive episode
  • A score of >= 20 on the HAMD-17 at the time of enrollment and at baseline
  • Episode duration will be greater than 4 weeks but not longer than 12 months.

Exclusion Criteria:

  • Insufficiently responding to >2 treatment strategies FDA/Health Canada-approved/guideline recommended for bipolar depression
  • Acute manic or mixed episode
  • An Axis I psychiatric disorder requiring primary clinical attention
  • Clinically significant medical illness
  • Treatment with minocycline or β-lactam antibiotics in the preceding 6 months
  • Hypersensitivity to minocycline or any other tetracycline
  • Physical injury requiring medical treatment or surgery in the last 6 months
  • Pregnant or breast-feeding
  • Inability to provide written informed consent.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01403662

Locations
Canada, Ontario
University Health Network Recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Joanna K Soczynska, HBSc, PhD Candidate    (416) 603-5800 ext 3726    joanna.soczynska@uhn.ca   
Contact: Hanna O Woldeyohannes, HBSc    (416) 603-5133    hanna.woldeyohannes@uhn.ca   
Principal Investigator: Roger S McIntyre, MD, FRCPC         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: Roger S McIntyre, MD, FRCPC University Health Network, Toronto
  More Information

Publications:
Responsible Party: Dr. Roger S. McIntyre, University Health Network and University of Toronto
ClinicalTrials.gov Identifier: NCT01403662     History of Changes
Other Study ID Numbers: 3420337
Study First Received: July 18, 2011
Last Updated: July 25, 2011
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
bipolar disorder
depression
major depression
bipolar I depression
bipolar II depression
bipolar I disorder
bipolar II disorder
minocycline
minocin

Additional relevant MeSH terms:
Depression
Depressive Disorder
Bipolar Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Affective Disorders, Psychotic
Minocycline
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014