Minocycline and Aspirin in the Treatment of Bipolar Depression

NCT ID: NCT01429272

Last Updated: 2018-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2015-09-30

Brief Summary

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

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.

Conditions

Bipolar Disorder Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo & Placebo

Placebo for minocycline \& placebo for aspirin

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo for minocycline and/or aspirin

minocycline & aspirin

Minocycline 100mg PO BID for 6 weeks \& Aspirin 81 mg PO BID for 6 weeks

Group Type: ACTIVE_COMPARATOR

Minocycline

Intervention Type: DRUG

100 mg po bid for 6 weeks

Aspirin

Intervention Type: DRUG

81 mg po bid for 6 weeks

Interventions

Minocycline

100 mg po bid for 6 weeks

Intervention Type: DRUG

Aspirin

81 mg po bid for 6 weeks

Intervention Type: DRUG

placebo

placebo for minocycline and/or aspirin

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanley Medical Research Institute

OTHER

Sponsor Role: collaborator

University of Oklahoma

OTHER

Sponsor Role: collaborator

Laureate Institute for Brain Research, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sheldon Preskorn, MD

Role: PRINCIPAL_INVESTIGATOR

Laureate Institute for Brain Research, Inc.

Locations

University of Kansas Medical Center Research Institute

Wichita, Kansas, United States

University of Oklahoma Department of Psychiatry

Tulsa, Oklahoma, United States

Laureate Institute for Brain Research

Tulsa, Oklahoma, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 22357572 (View on PubMed)

Related Links

http://www.laureateinstitute.org/

Related Info

Other Identifiers

LIBR 2011-002

Identifier Type: -

Identifier Source: org_study_id