Immuno-Genetic, Inflammation, Retro-Virus, Environment

Schizophrenia Clinical Trial

— I-Give  

Official title:

Immuno-Génétique, Inflammation, Retro-Virus, Environnement

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02878408
• Other study ID #: I-Give
• Secondary ID: IDRCB : 2013-A01
• Status: Recruiting
• Phase: N/A
• Start date: November 2014
• Est. completion date: November 2025

Study information

• Verified date: February 2024
• Source: Fondation FondaMental
• Contact: Marion Leboyer, Pr
• Phone: (33) 1 49 81 38 22
• Email: marion.leboyer[@]fondation-fondamental.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Immunology combined to neurobiology now offer prominent tools to yield biomarkers, so far missing in psychiatry, and to design innovative treatment approaches based on the discovery of new molecular and cellular targets. As Bipolar Disorder and Schizophrenia are now known to be significantly associated with neuro-inflammation, the project I-GIVE will combine multidisciplinary approaches (clinical, viral, immunological, genetic) to explore a global hypothesis placing the Human Endogenous Retro-Virus, HERV-W, at the crossroads between susceptibility to environmental factors (such as winter-spring births, infections, urbanicity…) and genetic factors controlling immune responses. Thus I-GIVE will allow identification of new biomarkers and their correlation with clinical profiles and immuno-inflammatory/immuno-genetic markers, and description of patho-physiological mechanisms of a psychiatric disorder. In addition, I-GIVE should help to design innovative treatments and foster personalized psychiatry tailored to the needs of each patient. Notably, monoclonal antibodies anti-HERV-W Env will be assessed in a preclinical model for their ability to slow, stop, or even reverse the progression of the psychosis in patients. I-GIVE project should thus lead to major results that will have strong impacts on the scientific community, pharmaceutical industries and, in a longer term, on improvement of patients suffering Bipolar Disorder or Schizophrenia and their family.

Description:

The investigators and others have been able to demonstrate that HERV-W envelope gene (Env) encodes a pro-inflammatory and neurotoxic protein after reactivation by environmental factors. In this context, the investigators have reported preliminary data showing an association between Human Endogenous Retroviruses type "W" family (HERV-W) and major psychotic disorder, bipolar disorder (BD) and schizophrenia (SZ) : In 2008, the investigators reported for the first time, the presence of ENV protein in the serum of 50 % of SZ patients associated with a chronic inflammatory status reflected by elevated serum level of C-Reactive Protein (CRP). The investigators have been able to confirm this finding and extend it to BD and showed an elevation of HERV-W RNA transcripts both in BD and SZ as compared to healthy controls. Furthermore, the investigators also observed for the first time that toxoplasma Gondii, known to be able to induce reactivation of HERV-W, is associated with an increased risk to develop BD (OR: 2.3) close to the one previously observed in SZ (OR= 2.17) The present project I-GIVE aims to extend and refine such findings and to obtain a proof of concept of the involvement of Human Endogenous Retrovirus elements in bipolar disorder and schizophrenia. I-GIVE is divided into four complementary scientific tasks: 1. assessing the systemic HERV-W (ENV and GAG) antigen serum levels and the RNA and DNA copy number variants of stabilized and acutely ill patients, 2. measuring the systemic associated immuno-inflammatory cascade in BD patients at different stages of the disorder and occurrence of medical comorbidities, 3. identifying the clinical characteristics of patients according to HERV-W expression and immuno-inflammatory profiles, 4. exploring the gene (immuno-genetic) x environment interactions that may modulate the immuno-inflammatory response Clinical and biological data from acute BP and SZ patients will be compared first with themselves at two different times. They will be compared also to healthy control's data, and third to stabilised BP and SZ patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1100
• Est. completion date: November 2025
• Est. primary completion date: November 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Bipolar disorder or Schizophrenia (according to Diagnostic and Statistical Manual of Mental Disorders IV)

Exclusion Criteria:

• pregnant women
• Vaccination within 4 precedent weeks
• Severe neurologic illness
• Immunosuppressing or immuno-modulating treatment.
• Infectious disease within 4 precedent weeks (including HIV 1 et 2, Hepatite B, C)
• Refuse to have HIV and hepatite B et C tests or to be informed of their results

Related Conditions & MeSH terms

• Bipolar Disorder
• Inflammation
• Schizophrenia

Intervention

Genetic:
• Blood sampling
supplementary blood sampling for analysis of: immuno-genetic, inflammatory process, retro-viruses activity, Questionaries about environment risk factors

Locations

Country	Name	City	State
France	Psychiatry Department of Perrens Hospital	Bordeaux
France	Clinical Investigations Center of Mondor Hospital	Créteil
France	Psychiatry Department of Mondor Hospital	Créteil
France	EPS Maison Blanche	Paris
France	Psychiatry Department of Widal Hospital	Paris
France	Psychiatry Department of R. Dubos Hospital	Pontoise

Sponsors (3)

Lead Sponsor	Collaborator
Pr. Marion Leboyer	Assistance Publique - Hôpitaux de Paris, National Research Agency, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HERV-W	measure of HERV retroviral DNA, RNA and envelop proteins	inclusion

External Links

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