Ignite Creation Date:
2024-05-06 @ 12:12 AM
Last Modification Date:
2024-10-26 @ 10:46 AM
Study NCT ID:
NCT01514682
Status:
COMPLETED
Last Update Posted:
2022-03-03
First Post:
2012-01-12
Brief Title:
Anti-Inflammatory Treatment of Schizophrenia
Sponsor:
University of Maryland Baltimore
Organization:
University of Maryland Baltimore
Study Overview
Official Title:
Anti-Inflammatory Combination Therapy for the Treatment of Schizophrenia
Status:
COMPLETED
Status Verified Date:
2022-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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 6p221 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 gmday 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 gmday and docosahexaenoic DHA 2 gmday 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 mgsday 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
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 gmday 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 gmday and docosahexaenoic DHA 2 gmday 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 mgsday 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None