Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
UNKNOWN
Clinical Phase
PHASE1/PHASE2
Total Enrollment
30 participants
Study Classification
INTERVENTIONAL
Study Start Date
2016-05-31
Study Completion Date
2023-12-31
Brief Summary
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This study is a Phase 1 clinical trial to determine the safety, tolerability, and efficacy of Siltuximab (Sylvant) as an adjunct to antipsychotic medications in stable outpatients with schizophrenia. Siltuximab (structural formula C6450H9932N1688O2016S50) is a recombinant chimeric (human-murine) anti-human interleukin-6 (IL-6) monoclonal antibody. Siltuximab is formulated as a concentrate for solution for infusion, and will be administered by intravenous infusion.
The investigators propose a 9-week randomized controlled trial of siltuximab, given in adjunct to antipsychotics, in N=30 stable outpatients with schizophrenia or schizoaffective disorder and evidence of increased inflammation in the peripheral blood (high-sensitivity C-reactive protein \[hsCRP\] \>0.5 mg/dL). The investigators hypothesize that adjunctive treatment with siltuximab will be associated with significant improvement in cognition compared to placebo in patients with schizophrenia, baseline IL-6 levels are higher in siltuximab-treated responders versus non-responders, and there will be greater decreases in hsCRP from baseline to week 6 in siltuximab-treated versus placebo-treated responders, with response defined as ≥0.5 SD improvement in cognition. Siltuximab is administered as an intravenous infusion every 3 weeks. Following a screening evaluation, participants will receive three infusions of siltuximab, one at baseline, another at week 3 of the study, and another at week 6. The investigators will measure changes in cognitive function and symptoms over a 9-week period. Complementing previous positive clinical trials of non-steroidal anti-inflammatory drugs, this would be a "proof-of-concept" study that targeting specific cytokines is a viable treatment for schizophrenia.
Interleukin 6 and its receptor were discovered and cloned at Osaka University, Japan, by Tadamitsu Kishimoto in the 1980s. Janssen Pharmaceuticals, Inc. began the clinical development of siltuximab for the treatment of multicentric Castleman's disease, a rare blood disorder. Other clinical studies with siltuximab have been conduced for patients with B-cell non-Hodgkin's lymphoma, multiple myeloma, and ovarian cancer.
In April 2014,siltuxiumab was approved by the U.S. Food and Drug Administration (US FDA) as Sylvant for human immunodeficiency virus (HIV)-negative and human herpesvirus-8 (HHV-8)-negative multicentric Castleman's disease.
The investigators propose a 9-week randomized controlled trial of siltuximab, given in adjunct to antipsychotics, in N=30 stable outpatients with schizophrenia or schizoaffective disorder and evidence of increased inflammation in the peripheral blood (high-sensitivity C-reactive protein \[hsCRP\] \>0.5 mg/dL). The investigators hypothesize that adjunctive treatment with siltuximab will be associated with significant improvement in cognition compared to placebo in patients with schizophrenia, baseline IL-6 levels are higher in siltuximab-treated responders versus non-responders, and there will be greater decreases in hsCRP from baseline to week 6 in siltuximab-treated versus placebo-treated responders, with response defined as ≥0.5 SD improvement in cognition. Siltuximab is administered as an intravenous infusion every 3 weeks. Following a screening evaluation, participants will receive three infusions of siltuximab, one at baseline, another at week 3 of the study, and another at week 6. The investigators will measure changes in cognitive function and symptoms over a 9-week period. Complementing previous positive clinical trials of non-steroidal anti-inflammatory drugs, this would be a "proof-of-concept" study that targeting specific cytokines is a viable treatment for schizophrenia.
Interleukin 6 and its receptor were discovered and cloned at Osaka University, Japan, by Tadamitsu Kishimoto in the 1980s. Janssen Pharmaceuticals, Inc. began the clinical development of siltuximab for the treatment of multicentric Castleman's disease, a rare blood disorder. Other clinical studies with siltuximab have been conduced for patients with B-cell non-Hodgkin's lymphoma, multiple myeloma, and ovarian cancer.
In April 2014,siltuxiumab was approved by the U.S. Food and Drug Administration (US FDA) as Sylvant for human immunodeficiency virus (HIV)-negative and human herpesvirus-8 (HHV-8)-negative multicentric Castleman's disease.
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Detailed Description
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A pathophysiological role for inflammation in schizophrenia has been one of the more enduring findings in the field. Recently, increased understanding of complex interactions between inflammation and the brain in other chronic diseases has better informed this relationship in schizophrenia. Several trials have found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs), in adjunct to antipsychotics, was associated with significant improvement in psychopathology in schizophrenia. Cytokines are key regulators of inflammation that exert effects in the periphery and the brain. Serum cytokine levels predicted response in two studies , and another study found a trend for improved cognition with adjunctive NSAID treatment. These findings provide important empirical support for a pathophysiological role for inflammation in some patients with schizophrenia. Two important limitations of these trials are that: a) the agents investigated have relevant off-target (i.e., non-immune) effects, and b) evidence of inflammation in the peripheral blood was not an inclusion criterion, which may have decreased the signal-to-noise ratio.
Schizophrenia is associated with impaired cognition, which persists despite current treatments, and is an important determinant of quality of life and overall function. Converging lines of evidence suggest that interleukin-6 (IL-6) is a promising therapeutic target for cognitive impairment in schizophrenia. IL-6 is a cytokine produced by peripheral blood leukocytes, and central nervous system (CNS) microglia and astrocytes. The IL-6 gene is a risk factor for schizophrenia and may impact on serum IL-6 levels. Blood and cerebrospinal fluid (CSF) IL-6 levels are altered in schizophrenia. IL-6 levels are associated with psychopathology and cognition in schizophrenia. Serum IL-6 levels are also increased in prodromal psychosis, drug-naïve first-episode psychosis (FEP) and first-degree relatives of patients with schizophrenia. In populations outside of schizophrenia, higher serum IL-6 levels are associated with poorer cognition, cognitive decline, and smaller hippocampal volume. In FEP and chronic schizophrenia, IL-6 levels are a significant predictor of smaller left hippocampal volume.
Evidence from animal studies also supports a putative role for IL-6 in the pathophysiology of schizophrenia. A single maternal injection of IL-6 during mouse pregnancy caused prepulse and latent inhibition deficits in the adult offspring. In rat prenatal immune activation models, adult offspring have increased serum IL-6 levels, at an age with homology to the usual age of onset of schizophrenia, that are modulated by antipsychotics. Ketamine-induced neuronal production of IL-6 is responsible for the activation of brain N=nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and dysfunction of fast-spiking parvalbumin-expressing interneurons.
Along with our other previous work, our preliminary studies provide strong evidence that IL-6 is a novel therapeutic target for cognitive impairment in schizophrenia, and demonstrate the feasibility of the proposed trial. Briefly, in 64 patients with schizophrenia, the investigators found higher blood IL-6 levels were a significant predictor of greater impairment on the Brief Assessment of Cognition in Schizophrenia (BACS) after controlling for multiple potential confounding factors. In an 8-week open-label trial in 6 subjects, tocilizumab (an anti-IL-6 receptor monoclonal antibody), given in adjunct to antipsychotics, was well tolerated and associated with significant improvement in BACS verbal fluency at 4 weeks, BACS digit symbol coding at 2, 4, and 8 weeks, and BACS composite score at 4 and 8 weeks.
In the first year following the submission, one clinical trial is planned. The investigators will conduct a 9-week randomized, double-blind, placebo-controlled trial to determine the safety, tolerability, and efficacy of siltuximab as an adjunct to antipsychotic medications in 30 stable outpatients with schizophrenia.
Siltuximab has not been used before in the treatment of schizophrenia, and using it this way is experimental. The risks that have been found in people with multicentric Castleman's disease are known, but there may be unknown risks when used in schizophrenia. Clinically significant adverse drug reactions include anaphylaxis, renal failure, and pneumonia. Known side effects of siltuximab that are common include: swelling of the extremities, fatigue, itching, rash, weight gain, diarrhea, abdominal pain, and joint or limb pain. The most common side effect of the drug is nasopharyngitis, which occurs in 63% of subjects with long-term exposure to Siltuximab.
Subjects with schizophrenia and schizoaffective disorder will be accessed from outpatient psychiatry clinic at Augusta University or other satellite collaborative sites. The study has 5 visits: screening, baseline, and weeks 3, 6, and 9. Subjects will be randomized equally to either siltuximab (n=15) or placebo (n=15), in adjunct to their current antipsychotic and other psychotropic medications. The study has 5 visits: screening, baseline, and weeks 3, 6, and 9. Subjects will be randomized equally to either siltuximab (n=15) or placebo (n=15), in adjunct to their current antipsychotic and other psychotropic medications. Subjects in the siltuximab group will receive an 11 mg/kg infusion at baseline, and weeks 3 and 6, as per the recommended dosing for multicentric Castleman's disease. Subjects in the placebo group will receive an infusion of normal saline (with the same packaging and volume as the siltuximab group) at baseline, and weeks 3 and 6. Subjects will be monitored for an additional 30 minutes following the completion of the infusion. Dr. Miller will monitor the subject throughout the infusion and the 30 minute post-infusion period. The investigators will contact the subjects by phone on days 1 and 7 after each infusion to assess for any infusion-related events. The investigators will assess cognition and psychopathology at baseline, and at weeks 3, 6, and 9. The investigators will also measure a multiplex panel of blood cytokines (including IL-6) and tryptophan catabolites at baseline, and at weeks 3, 6, and 9. At Screening, all subjects will be administered the evaluation to sign consent, informed consent, and the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders (DSM) psychosis and affective disorders modules. The investigators will perform a medical history and physical exam, fasting labs (complete blood count \[CBC\], complete metabolic profile \[CMP\], hsCRP, lipid panel, urinalysis, and urine drug screen (UDS), hepatitis panel, HIV, rapid plasma reagin \[RPR\], and human chorionic gonadotropin \[hCG\] in females), a tuberculin skin test, and a 12-lead electrocardiogram. At Baseline, the investigators will perform the Positive And Negative Syndrome Scale (PANSS), BACS, and Clinical Global Impressions scale (CGI), Calgary Depression Scale (CDS) and Short Form Health Survey (SF-36) and draw blood for IL-6 and high-sensitivity c-reactive protein (hsCRP). At Week 3, 6, and 9, the investigators will perform an interval history, physical exam, PANSS, BACS, CGI, CDS, SF-36, and obtain fasting labs (CBC, CMP, lipid panel, hsCRP, urinalysis, UDS, and hCG in females). Different versions of the BACS will be used to avoid practice effects. Patients will be withdrawn if they meet any exclusion criterion at any time point.
Schizophrenia is associated with impaired cognition, which persists despite current treatments, and is an important determinant of quality of life and overall function. Converging lines of evidence suggest that interleukin-6 (IL-6) is a promising therapeutic target for cognitive impairment in schizophrenia. IL-6 is a cytokine produced by peripheral blood leukocytes, and central nervous system (CNS) microglia and astrocytes. The IL-6 gene is a risk factor for schizophrenia and may impact on serum IL-6 levels. Blood and cerebrospinal fluid (CSF) IL-6 levels are altered in schizophrenia. IL-6 levels are associated with psychopathology and cognition in schizophrenia. Serum IL-6 levels are also increased in prodromal psychosis, drug-naïve first-episode psychosis (FEP) and first-degree relatives of patients with schizophrenia. In populations outside of schizophrenia, higher serum IL-6 levels are associated with poorer cognition, cognitive decline, and smaller hippocampal volume. In FEP and chronic schizophrenia, IL-6 levels are a significant predictor of smaller left hippocampal volume.
Evidence from animal studies also supports a putative role for IL-6 in the pathophysiology of schizophrenia. A single maternal injection of IL-6 during mouse pregnancy caused prepulse and latent inhibition deficits in the adult offspring. In rat prenatal immune activation models, adult offspring have increased serum IL-6 levels, at an age with homology to the usual age of onset of schizophrenia, that are modulated by antipsychotics. Ketamine-induced neuronal production of IL-6 is responsible for the activation of brain N=nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and dysfunction of fast-spiking parvalbumin-expressing interneurons.
Along with our other previous work, our preliminary studies provide strong evidence that IL-6 is a novel therapeutic target for cognitive impairment in schizophrenia, and demonstrate the feasibility of the proposed trial. Briefly, in 64 patients with schizophrenia, the investigators found higher blood IL-6 levels were a significant predictor of greater impairment on the Brief Assessment of Cognition in Schizophrenia (BACS) after controlling for multiple potential confounding factors. In an 8-week open-label trial in 6 subjects, tocilizumab (an anti-IL-6 receptor monoclonal antibody), given in adjunct to antipsychotics, was well tolerated and associated with significant improvement in BACS verbal fluency at 4 weeks, BACS digit symbol coding at 2, 4, and 8 weeks, and BACS composite score at 4 and 8 weeks.
In the first year following the submission, one clinical trial is planned. The investigators will conduct a 9-week randomized, double-blind, placebo-controlled trial to determine the safety, tolerability, and efficacy of siltuximab as an adjunct to antipsychotic medications in 30 stable outpatients with schizophrenia.
Siltuximab has not been used before in the treatment of schizophrenia, and using it this way is experimental. The risks that have been found in people with multicentric Castleman's disease are known, but there may be unknown risks when used in schizophrenia. Clinically significant adverse drug reactions include anaphylaxis, renal failure, and pneumonia. Known side effects of siltuximab that are common include: swelling of the extremities, fatigue, itching, rash, weight gain, diarrhea, abdominal pain, and joint or limb pain. The most common side effect of the drug is nasopharyngitis, which occurs in 63% of subjects with long-term exposure to Siltuximab.
Subjects with schizophrenia and schizoaffective disorder will be accessed from outpatient psychiatry clinic at Augusta University or other satellite collaborative sites. The study has 5 visits: screening, baseline, and weeks 3, 6, and 9. Subjects will be randomized equally to either siltuximab (n=15) or placebo (n=15), in adjunct to their current antipsychotic and other psychotropic medications. The study has 5 visits: screening, baseline, and weeks 3, 6, and 9. Subjects will be randomized equally to either siltuximab (n=15) or placebo (n=15), in adjunct to their current antipsychotic and other psychotropic medications. Subjects in the siltuximab group will receive an 11 mg/kg infusion at baseline, and weeks 3 and 6, as per the recommended dosing for multicentric Castleman's disease. Subjects in the placebo group will receive an infusion of normal saline (with the same packaging and volume as the siltuximab group) at baseline, and weeks 3 and 6. Subjects will be monitored for an additional 30 minutes following the completion of the infusion. Dr. Miller will monitor the subject throughout the infusion and the 30 minute post-infusion period. The investigators will contact the subjects by phone on days 1 and 7 after each infusion to assess for any infusion-related events. The investigators will assess cognition and psychopathology at baseline, and at weeks 3, 6, and 9. The investigators will also measure a multiplex panel of blood cytokines (including IL-6) and tryptophan catabolites at baseline, and at weeks 3, 6, and 9. At Screening, all subjects will be administered the evaluation to sign consent, informed consent, and the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders (DSM) psychosis and affective disorders modules. The investigators will perform a medical history and physical exam, fasting labs (complete blood count \[CBC\], complete metabolic profile \[CMP\], hsCRP, lipid panel, urinalysis, and urine drug screen (UDS), hepatitis panel, HIV, rapid plasma reagin \[RPR\], and human chorionic gonadotropin \[hCG\] in females), a tuberculin skin test, and a 12-lead electrocardiogram. At Baseline, the investigators will perform the Positive And Negative Syndrome Scale (PANSS), BACS, and Clinical Global Impressions scale (CGI), Calgary Depression Scale (CDS) and Short Form Health Survey (SF-36) and draw blood for IL-6 and high-sensitivity c-reactive protein (hsCRP). At Week 3, 6, and 9, the investigators will perform an interval history, physical exam, PANSS, BACS, CGI, CDS, SF-36, and obtain fasting labs (CBC, CMP, lipid panel, hsCRP, urinalysis, UDS, and hCG in females). Different versions of the BACS will be used to avoid practice effects. Patients will be withdrawn if they meet any exclusion criterion at any time point.
Conditions
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Schizophrenia
Psychotic Disorders
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
DOUBLE
Participants
Investigators
Study Groups
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Treatment Group
Subjects in the siltuximab group will receive an 11 mg/kg infusion at baseline, and weeks 3 and 6, as per the recommended dosing for multicentric Castleman's disease
Group Type
ACTIVE_COMPARATOR
Siltuximab
Intervention Type
DRUG
Investigational agent
Control Group
Subjects in the placebo group will receive an infusion of normal saline (with the same packaging and volume as the siltuximab group) at baseline, and weeks 3 and 6.
Group Type
PLACEBO_COMPARATOR
normal saline
Intervention Type
DRUG
Placebo
Interventions
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Siltuximab
Investigational agent
Intervention Type
DRUG
normal saline
Placebo
Intervention Type
DRUG
Other Intervention Names
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Sylvant
0.9% NS
Eligibility Criteria
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Inclusion Criteria
* capable of giving informed consent
* diagnosis of schizophrenia or schizoaffective disorder
* stable based on clinical judgment
* taking a non-clozapine antipsychotic
* on the same psychotropic medications for \>4 weeks
* hsCRP \>0.3 mg/dL at the screening visit
* diagnosis of schizophrenia or schizoaffective disorder
* stable based on clinical judgment
* taking a non-clozapine antipsychotic
* on the same psychotropic medications for \>4 weeks
* hsCRP \>0.3 mg/dL at the screening visit
Exclusion Criteria
* imminent danger to self/others
* antibiotic use in the past 2 weeks
* current scheduled use of immunomodulatory agents
* history of an immune disorder
* illicit drug use in the past 30 days
* any unstable or untreated medical condition
* history of gastrointestinal ulcers, diverticulitis, malignancy, CNS demyelinating disorder, seizure disorder, or exposure to tuberculosis
* low absolute neutrophil (\<2000) or platelet (\<100,000) count
* abnormal hepatic function (AST or ALT \>1.5 times the upper limit of normal) or renal function (BUN or creatinine \>1.5 times the upper limit of normal)
* any abnormal lab test result judged to be clinically significant
* active or chronic infections
* pregnancy, breast feeding, or female of child-bearing potential who is not using any contraception.
* antibiotic use in the past 2 weeks
* current scheduled use of immunomodulatory agents
* history of an immune disorder
* illicit drug use in the past 30 days
* any unstable or untreated medical condition
* history of gastrointestinal ulcers, diverticulitis, malignancy, CNS demyelinating disorder, seizure disorder, or exposure to tuberculosis
* low absolute neutrophil (\<2000) or platelet (\<100,000) count
* abnormal hepatic function (AST or ALT \>1.5 times the upper limit of normal) or renal function (BUN or creatinine \>1.5 times the upper limit of normal)
* any abnormal lab test result judged to be clinically significant
* active or chronic infections
* pregnancy, breast feeding, or female of child-bearing potential who is not using any contraception.
Minimum Eligible Age
18 Years
Maximum Eligible Age
55 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Stanley Medical Research Institute
OTHER
Sponsor Role
collaborator
Brian Miller
OTHER
Sponsor Role
lead
Responsible Party
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Brian Miller
Associate Professor
Responsibility Role
SPONSOR_INVESTIGATOR
Locations
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Augusta University
Augusta, Georgia, United States
Site Status
RECRUITING
Countries
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United States
Central Contacts
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Facility Contacts
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References
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Muller N. COX-2 inhibitors as antidepressants and antipsychotics: clinical evidence. Curr Opin Investig Drugs. 2010 Jan;11(1):31-42.
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Muller N, Riedel M, Schwarz MJ, Engel RR. Clinical effects of COX-2 inhibitors on cognition in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2005 Apr;255(2):149-51. doi: 10.1007/s00406-004-0548-4. Epub 2004 Nov 19.
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Paul-Samojedny M, Kowalczyk M, Suchanek R, Owczarek A, Fila-Danilow A, Szczygiel A, Kowalski J. Functional polymorphism in the interleukin-6 and interleukin-10 genes in patients with paranoid schizophrenia--a case-control study. J Mol Neurosci. 2010 Sep;42(1):112-9. doi: 10.1007/s12031-010-9365-6.
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BACKGROUND
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BACKGROUND
Sasayama D, Hattori K, Wakabayashi C, Teraishi T, Hori H, Ota M, Yoshida S, Arima K, Higuchi T, Amano N, Kunugi H. Increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and those with major depressive disorder. J Psychiatr Res. 2013 Mar;47(3):401-6. doi: 10.1016/j.jpsychires.2012.12.001. Epub 2013 Jan 3.
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BACKGROUND
Krause DL, Wagner JK, Wildenauer A, Matz J, Weidinger E, Riedel M, Obermeier M, Gruber R, Schwarz M, Muller N. Intracellular monocytic cytokine levels in schizophrenia show an alteration of IL-6. Eur Arch Psychiatry Clin Neurosci. 2012 Aug;262(5):393-401. doi: 10.1007/s00406-012-0290-2. Epub 2012 Jan 21.
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Frydecka D, Misiak B, Pawlak-Adamska E, Karabon L, Tomkiewicz A, Sedlaczek P, Kiejna A, Beszlej JA. Interleukin-6: the missing element of the neurocognitive deterioration in schizophrenia? The focus on genetic underpinnings, cognitive impairment and clinical manifestation. Eur Arch Psychiatry Clin Neurosci. 2015 Sep;265(6):449-59. doi: 10.1007/s00406-014-0533-5. Epub 2014 Sep 12.
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Miller B, Mellor A, Buckley PF. Interleukin-6 and Cognition in Non-Affective Psychosis. Schizophrenia Bulletin 2013(39): S242-S243.
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Stojanovic A, Martorell L, Montalvo I, Ortega L, Monseny R, Vilella E, Labad J. Increased serum interleukin-6 levels in early stages of psychosis: associations with at-risk mental states and the severity of psychotic symptoms. Psychoneuroendocrinology. 2014 Mar;41:23-32. doi: 10.1016/j.psyneuen.2013.12.005. Epub 2013 Dec 14.
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Sasayama D, Hori H, Teraishi T, Hattori K, Ota M, Matsuo J, Kawamoto Y, Kinoshita Y, Amano N, Kunugi H. Association of cognitive performance with interleukin-6 receptor Asp358Ala polymorphism in healthy adults. J Neural Transm (Vienna). 2012 Mar;119(3):313-8. doi: 10.1007/s00702-011-0709-3. Epub 2011 Aug 31.
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Frodl T, Carballedo A, Hughes MM, Saleh K, Fagan A, Skokauskas N, McLoughlin DM, Meaney J, O'Keane V, Connor TJ. Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder. Transl Psychiatry. 2012 Mar 13;2(3):e88. doi: 10.1038/tp.2012.14.
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Mondelli V, Cattaneo A, Murri MB, Di Forti M, Handley R, Hepgul N, Miorelli A, Navari S, Papadopoulos AS, Aitchison KJ, Morgan C, Murray RM, Dazzan P, Pariante CM. Stress and inflammation reduce brain-derived neurotrophic factor expression in first-episode psychosis: a pathway to smaller hippocampal volume. J Clin Psychiatry. 2011 Dec;72(12):1677-1684. doi: 10.4088/JCP.10m06745. Epub 2011 May 18.
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BACKGROUND
Romero E, Ali C, Molina-Holgado E, Castellano B, Guaza C, Borrell J. Neurobehavioral and immunological consequences of prenatal immune activation in rats. Influence of antipsychotics. Neuropsychopharmacology. 2007 Aug;32(8):1791-804. doi: 10.1038/sj.npp.1301292. Epub 2006 Dec 20.
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BACKGROUND
Romero E, Guaza C, Castellano B, Borrell J. Ontogeny of sensorimotor gating and immune impairment induced by prenatal immune challenge in rats: implications for the etiopathology of schizophrenia. Mol Psychiatry. 2010 Apr;15(4):372-83. doi: 10.1038/mp.2008.44. Epub 2008 Apr 15.
Reference Type
BACKGROUND
Behrens MM, Ali SS, Dugan LL. Interleukin-6 mediates the increase in NADPH-oxidase in the ketamine model of schizophrenia. J Neurosci. 2008 Dec 17;28(51):13957-66. doi: 10.1523/JNEUROSCI.4457-08.2008.
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BACKGROUND
Miller BJ, Culpepper N, Rapaport MH. C-reactive protein levels in schizophrenia: a review and meta-analysis. Clin Schizophr Relat Psychoses. 2014 Jan;7(4):223-30. doi: 10.3371/CSRP.MICU.020813.
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BACKGROUND
Miller BJ, Mellor A, Buckley P. Total and differential white blood cell counts, high-sensitivity C-reactive protein, and the metabolic syndrome in non-affective psychoses. Brain Behav Immun. 2013 Jul;31:82-9. doi: 10.1016/j.bbi.2012.08.016. Epub 2012 Sep 11.
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BACKGROUND
Miller BJ, Kandhal P, Rapaport MH, Mellor A, Buckley P. Total and differential white blood cell counts, high-sensitivity C-reactive protein, and cardiovascular risk in non-affective psychoses. Brain Behav Immun. 2015 Mar;45:28-35. doi: 10.1016/j.bbi.2014.12.005. Epub 2014 Dec 24.
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Miller BJ, Dias JK, Lemos HP, Buckley PF. An open-label, pilot trial of adjunctive tocilizumab in schizophrenia. J Clin Psychiatry. 2016 Feb;77(2):275-6. doi: 10.4088/JCP.15l09920. No abstract available.
Reference Type
BACKGROUND
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
15T-005
Identifier Type: -
Identifier Source: org_study_id
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