Minocycline and Aspirin in the Treatment of Bipolar Depression (Minocycline)

The purpose of this study is to determine whether minocycline and aspirin are effective in the treatment of depression in individuals with bipolar disorder.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder Depression
• Intervention / Treatment: Drug: placebo; Drug: Minocycline; Drug: Aspirin

Detailed Description

Abstract:

New medication classes are needed to improve treatment effectiveness in the depressed phase of bipolar disorder (BD). Extant evidence suggests that BD is not only characterized by reduced monoaminergic signaling, but also by neural changes such as dendritic remodeling, demyelination, and glial and neuronal cell loss. These changes have been hypothesized to result from chronic inflammation, based partly on convergent evidence that proinflammatory cytokines are elevated in depressed patients with BD. The principal aims of the proposed research is to evaluate the antidepressant efficacy in bipolar depression of minocycline, a drug with neuroprotective and immune-modulating properties, and of aspirin, at doses expected to selectively inhibit cyclooxygenase 1 (COX-1), within the context of a randomized, double-blind, placebo-controlled, parallel-group clinical trial following a 2 x 2 design.

Specific Aims Specific Aim 1: To evaluate the efficacy of augmentation therapy with minocycline and/or aspirin for bipolar depression.

The investigators will test the hypothesis that compared with placebo, participants receiving minocycline and/ or aspirin will show a greater treatment response rate (defined as a >50% increase on the MADRS for the final two consecutive visits).

Specific Aim 2: To investigate the relationship between the response to minocycline, aspirin and markers of inflammation (serum concentrations of IL-6 and CRP).

The investigators will test the hypotheses that: a) minocycline treatment will reduce inflammation to a greater extent than placebo; b) during minocycline treatment the change in inflammatory cytokine expression will correlate with the change in depression ratings; c) the baseline elevation of inflammatory markers will predict greater antidepressant response to minocycline.

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Wichita, Kansas, United States, 67207
      • University of Kansas Medical Center Research Institute
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74135
      • University of Oklahoma Department of Psychiatry
    • Tulsa, Oklahoma, United States, 74136-3326
      • Laureate Institute for Brain Research

Participation Criteria

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:

One hundred and twenty male or female outpatients between 18 and 65 years of age, who meet DSM-IV-TR criteria for BD (type I or II or NOS) and for a current major depressive episode will be recruited. The depressive syndrome must have been present for at least 4 weeks and the minimum threshold for depression severity will be set at a Quick Inventory of Depressive Symptomatology (QID-C16) score >10. Subjects will provide written informed consent as approved by the Western Institutional Review Board.

Exclusion Criteria:

(a) Illness onset after 40 years of age; (b) serious risk of suicide; (c) current delusions or hallucinations sufficient to interfere with the capacity to provide informed consent; (d) current manic symptoms of sufficient severity to pose a substantial risk of the development of a manic episode; (e) current treatment with more than four psychotropic medications; (f) medical illness including hepatic impairment, renal dysfunction, bleeding diatheses, cerebrovascular disease, hypertension or diabetes mellitus that is inadequately controlled by diet and/or medication, or known active peptic ulcer disease; (g) abuse of drugs or alcohol within the preceding 6 months, or substance dependence within the last year; (h) daily alcoholic beverage consumption equivalent to >3 oz. of alcohol; (i) known allergies or hypersensitivities to tetracycline antibiotics, aspirin or other NSAIDs; (j) current use of drugs that could increase the risks associated with aspirin or minocycline administration, (k) chronic infection, (l) use of antibiotics, (m) pregnant or nursing women, (n) asthma which in the opinion of the investigator would increase the likelihood of an asthmatic attack, and (o) regular use of steroidal or non-steroidal anti-inflammatory medications (occasional use of NSAIDS was allowed).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo & Placebo; Placebo for minocycline & placebo for aspirin	Drug: placebo; placebo for minocycline and/or aspirin
Active Comparator: minocycline & aspirin; Minocycline 100mg PO BID for 6 weeks & Aspirin 81 mg PO BID for 6 weeks	Drug: Minocycline; 100 mg po bid for 6 weeks; Drug: Aspirin; 81 mg po bid for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Response	Response to treatment defined as a >50% decrease in Montgomery-Asberg Depression Rating Scale scores for the final two consecutive visits.	Six weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission Rate	Remission defined as a score of <11 on Montgomery-Asberg Depression Rating Scale scores for the final two consecutive visits.	Six weeks

Collaborators and Investigators

• Sponsor: Laureate Institute for Brain Research, Inc.
• Collaborators: University of Oklahoma; Stanley Medical Research Institute
• Investigators: Principal Investigator: Sheldon Preskorn, MD, Laureate Institute for Brain Research, Inc.

Publications and helpful links

General Publications

• Savitz J, Preskorn S, Teague TK, Drevets D, Yates W, Drevets W. Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2x2 clinical trial. BMJ Open. 2012 Feb 22;2(1):e000643. doi: 10.1136/bmjopen-2011-000643. Print 2012.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: September 2, 2011
• First Submitted That Met QC Criteria: September 6, 2011
• First Posted (Estimate): September 7, 2011

Study Record Updates

• Last Update Posted (Actual): January 11, 2018
• Last Update Submitted That Met QC Criteria: December 13, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Bipolar Disorder; Minocycline
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Depression; Depressive Disorder; Bipolar Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Anti-Bacterial Agents; Aspirin; Minocycline
• Other Study ID Numbers: LIBR 2011-002