Clinical trial NCT01429272: Minocycline and Aspirin in the Treatment of Bipolar Depression
Official title: Minocycline and Aspirin in the Treatment of Bipolar Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar Disorder Depression
Keywords: Bipolar Disorder
Minocycline
Lead sponsor: Laureate Institute for Brain Research, Inc.
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
name: University of Oklahoma
First posted: 2011-09-07
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Treatment Response
timeFrame: Six weeks
Secondary outcomes:
measure: Remission Rate
timeFrame: Six weeks
Other outcomes:
Locations:
city: Wichita
country: United States
facility: University of Kansas Medical Center Research Institute
state: Kansas
city: Tulsa
country: United States
facility: University of Oklahoma Department of Psychiatry
state: Oklahoma
city: Tulsa
country: United States
facility: Laureate Institute for Brain Research
state: Oklahoma
Study officials:
affiliation: Laureate Institute for Brain Research, Inc.
name: Sheldon Preskorn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.