NCT01514682

Anti-Inflammatory Treatment of Schizophrenia

Anti-Inflammatory Combination Therapy for the Treatment of Schizophrenia

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: University of Maryland, Baltimore · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

Despite current antipsychotic treatment, the majority of people with schizophrenia continue to exhibit persistent positive and negative symptoms and cognitive impairments. An alternative approach to the use of psychotropic agents for the treatment of persistent symptoms is the use of anti-inflammatory agents to reverse the pro-inflammatory state hypothesized to underlie the symptom and sign manifestations of the illness. The investigators primary hypothesis is that add-on anti-inflammatory combination therapy will have significant beneficial effects on persistent positive symptoms and cognitive impairments. The investigators secondary hypotheses are: 1. add-on anti-inflammatory combination therapy will be associated with improvements in depressive and negative symptoms and a reduction in pro-inflammatory cytokines 2. add-on anti-inflammatory combination therapy compared to placebo will not be associated with elevated adverse risk.

Detailed description

Schizophrenia has been hypothesized to be due, in part, to disruptions of normal immune system and inflammatory responses to viral or bacterial infections or other stimuli of these systems. Epidemiological and clinical studies have provided extensive evidence that perinatal exposure to infection contributes to the etiology of schizophrenia. The recent reports of associations between markers of single nucleotide polymorphisms located within the major histocompatibility complex on chromosome 6p22.1 and schizophrenia provide further support for etiological hypotheses of immune system dysfunction in schizophrenia. There are a large number of reports that suggest that people with schizophrenia have altered cytokine levels, with one or more studies reporting elevated levels of the pro-inflammatory cytokines: IL-1β, IL-6, IL-12, CRP, IFN-γ, and TNF-α; and reduced levels of the anti-inflammatory cytokine: IL-10. In this study we examine the use of combination anti-inflammatory therapy as an intervention in patients with schizophrenia. We will use 1. Salsalate, 4 gm/day. Salsalate is a potent inhibitor of nuclear transcription factor NF-κB activation. NF-κB is activated by pro-inflammatory cytokines; 2. Omega-3-fatty acids eicosapentaenoic (EPA; 2 gm/day) and docosahexaenoic (DHA; 2 gm/day). Omega-3-fatty acids exert their anti-inflammatory effects through their oxygenation into resolvins or protectins, which are potent anti-inflammatory agents; 3. Fluvastatin, 40 mgs/day. Fluvastatin is a lipid-lowering drugs, which acts through the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA). Fluvastatin may also exert anti-inflammatory effects independent of its lipid-lowering effects via a mechanism involving HMG-CoA inhibition and decreased NF-κB activation. We have chosen to use combination therapy with three different classes of anti-inflammatory agents to address the potential benefit of this therapeutic approach for persistent positive symptoms and cognitive impairments. The three agents have unique anti-inflammatory mechanisms of action, which we believe offers the most robust evaluation of this therapeutic approach and maximizes the likelihood of eliciting pronounced therapeutic effects.

Conditions

• Schizophrenia

Interventions

Type	Name	Description
DRUG	Anti-inflammatory Combination Therapy	1. salsalate: target dose 4 gm/day, administered in two divided doses of 2 gm in the morning and 2 gm in the evening 2. fluvastatin: target dose 40 mg/day, administered in a single evening dose 3. combined omega-3-fatty acid preparation of EPA and DHA; target dose EPA 2 gm/day and DHA 2 gm/day administered in a single evening dose
DRUG	Placebo	Non-medication pills; To be taken in morning and evening intervals.

Timeline

• Start date: 2012-06-01
• Primary completion: 2017-04-17
• Completion: 2017-04-17
• First posted: 2012-01-23
• Last updated: 2022-03-03
• Results posted: 2018-03-29

Locations

1 site across 1 country: United States