Study of the Activation of Proinflammatory Pathways of Toll-like Receptors in Schizophrenia Patients

NCT02897167 | Completed

• 1 other identifier: PAFIP_TLR
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The study of immune pathways involved in the etiopathogeny of schizophrenia would be an important advance to understand the mechanisms involved in the development of this disease and it would be a turning point in drug therapy. Until now, the mechanism of action of antipsychotics focused on the blockade or modulation of brain dopaminergic pathways. If immunological pathways responsible for neuroinflammation and neurodegeneration which involve alterations in different areas and brain pathways (including dopaminergic pathways) are discovered, investigators could develop new treatments that act on these new targets, allowing to delay the onset of the first psychotic episode and improve the evolution and impact of this disease.

Conditions

Schizophrenia; Mental Disorders; Psychotic Disorders

Keywords

Psychosis; Antipsychotic Agents; Immunology; Schizophrenia Spectrum and Other Psychotic Disorders

Outcome Measures

Primary Outcomes (1)

• Measure the expression of proinflammatory molecules of activation pathways of TLRs in patients and controls using the Luminex xMAP technology: a comparative effect of Risperidone vs Aripiprazole.

  The Milliplex Human High Sensitivity T Cell Magnetic Bead Kit will be used to analyze the proinflammatory molecules. This kit includes response cytokines (Th1, Th2, Th17 and regulatory) and cytokines secreted by macrophage cells and myeloid lineage. It allows a balance of pro and anti-inflammatory cytokines. Luminex is an automated flow cytometer with an open technology that allows various tests to measure different biological parameters, reducing time, handling and cost overruns compared to more traditional methods such as Western Blot, enzyme-linked immunosorbent assay (ELISA) or traditional protein arrays. The methodology uses tests in the microsphere surface or magnetic beads of 5.6 um diameter which emit fluorescence and it is detected in a compact analyzer (Luminex).

  3 months

Secondary Outcomes (2)

• Assessment the expression of genes encoding proinflammatory pathways of TLRs in patients and controls using the Luminex xMAP technology.

  3 months

• Measure the functionality of proinflammatory pathways of TLRs in patients and controls after direct cell stimulation.

  3 months

Other Outcomes (1)

• Compare the long-term evolution of patients with varying degrees of activation of immune system using the Luminex xMAP technology.

  3 years

Study Arms (3)

PAFIP patients (1)

Individuals included in the First Episode Psychosis Clinical Program (PAFIP) between June 2011 and February 2016. Retrospective study of frozen samples: samples at baseline and 3 months will be analyzed.

Genetic: Retrospective study of frozen samples

PAFIP patients (2)

Individuals included in the First Episode Psychosis Clinical Program (PAFIP) between September 2016 and September 2017. Prospective study of fresh samples: samples at baseline and 3 months will be analyzed.

Genetic: Prospective study of fresh samples

Controls

Healthy subjects without psychotic disorder.

Genetic: Retrospective study of frozen samples

Interventions

Retrospective study of frozen samples GENETIC

Frozen samples of serum and peripheral blood mononuclear cell (PBMC) stored in the Biobank Valdecilla will be selected.

Controls; PAFIP patients (1)

Prospective study of fresh samples GENETIC

Samples of serum and cells will be drawn.

PAFIP patients (2)

Eligibility Criteria

• Age: 15 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Individuals included in the First Episode Psychosis Clinical Program (PAFIP) at the University Hospital Marqués de Valdecilla (Santander - Cantabria, Spain) between June 2011 and September 2017.

You may qualify if:

• Patients included in the First Episode Psychosis Clinical Program (PAFIP) between June 2011 and September 2017.
• Living in the catchment area.
• Experiencing their first episode of psychosis before 40 years.
• Meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for a principal diagnosis of schizophreniform, schizophrenia, schizoaffective, brief reactive psychosis, or psychosis non otherwise specified.
• No prior treatment with antipsychotic medication or, if previously treated, a total life time of adequate antipsychotic treatment of less than 6 weeks.

You may not qualify if:

• Meeting DSM-V criteria for drug dependence.
• Meeting DSM-V criteria for mental retardation.
• Having a history of neurological disease or head injury.

Sponsors & Collaborators

• Fundación Marques de Valdecilla: lead
• Centro de Investigación Biomédica en Red de Salud Mental: collaborator
• Instituto de Investigación Marqués de Valdecilla: collaborator

Study Sites (1)

University Hospital Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Related Publications (1)

• Pardo-de-Santayana G, Juncal-Ruiz M, Vazquez-Bourgon J, Riesco-Davila L, Ortiz-Garcia de la Foz V, Pelayo-Teran JM, Lopez-Hoyos M, Crespo-Facorro B. Active psychosis and pro-inflammatory cytokines in first-episode of psychosis. J Psychiatr Res. 2021 Feb;134:150-157. doi: 10.1016/j.jpsychires.2020.12.060. Epub 2020 Dec 22.

  PMID: 33385633 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum and peripheral blood mononuclear cell (PBMC)

MeSH Terms

Conditions

Schizophrenia; Mental Disorders; Psychotic Disorders; Schizophrenia Spectrum and Other Psychotic Disorders

Study Officials

• Benedicto Crespo-Facorro, Professor

  University Hospital Marqués de Valdecilla, IDIVAL, Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain. CIBERSAM Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: September 7, 2016
• First Posted: September 13, 2016
• Study Start: August 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: March 1, 2019
• Last Updated: February 17, 2020

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)