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

December 15, 2016 updated by: Roger McIntyre, University Health Network, Toronto

A Pilot, Open-label, 8-Week Study Evaluating the Efficacy, Safety, and Tolerability of Adjunctive Minocycline for the Treatment of Bipolar Depression

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5T 2S8
        • University Health Network

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Minocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline to week 8 on the Montgomery Asberg Depression Rating Scale (MADRS)
Time Frame: Baseline, Week 1, 2, 4, 6, 8
The MADRS assesses depressive symptoms
Baseline, Week 1, 2, 4, 6, 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
The HAMD-17 assesses depressive symptoms
Baseline, Week 1, 2, 4, 6, 8
Change from baseline to week 8 on the Somatic Symptom Inventory (SSI)
Time Frame: Baseline, Week 8
Baseline, Week 8
Change from baseline to week 8 on the Clinical Global Impression (CGI) Rating Scale
Time Frame: Baseline, Week 1, 2, 4, 6, 8
Baseline, Week 1, 2, 4, 6, 8
Change from baseline to week 8 in the in neurocognitive function
Time Frame: Baseline, Week 8
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
Baseline, Week 8
Monitoring of Side-effects from baseline to week 8 with the Toronto Side Effect Scale (TSES)
Time Frame: Week 1, 2, 4, 6, 8
Week 1, 2, 4, 6, 8
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
Baseline, Week 1, 2, 4, 6, 8
Change from baseline to week 8 in concentrations of pro-and anti-inflammatory cytokines (e.g. TNFα, IL-1β, IL-2, IL-6, IL8, IFNγ, IL-4, IL-5, IL-10)
Time Frame: Baseline, Week 8
Baseline, Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Roger S McIntyre, MD, FRCPC, University Health Network, Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2011

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

July 18, 2011

First Submitted That Met QC Criteria

July 25, 2011

First Posted (Estimate)

July 27, 2011

Study Record Updates

Last Update Posted (Estimate)

December 19, 2016

Last Update Submitted That Met QC Criteria

December 15, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3420337

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Bipolar Disorder

Clinical Trials on Minocycline

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Moldova

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe