Clinical trial NCT02878408: Immuno-Genetic, Inflammation, Retro-Virus, Environment
Official title: Immuno-Génétique, Inflammation, Retro-Virus, Environnement
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bipolar Disorder
Schizophrenia
Lead sponsor: Fondation FondaMental
Sponsor class: OTHER
Collaborators: name: National Research Agency, France
name: Assistance Publique - Hôpitaux de Paris
First posted: 2016-08-25
Enrollment: 1100
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: HERV-W
timeFrame: inclusion
Secondary outcomes:
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Psychiatry Department of Perrens Hospital
city: Créteil
country: France
facility: Clinical Investigations Center of Mondor Hospital
city: Créteil
country: France
facility: Psychiatry Department of Mondor Hospital
city: Paris
country: France
facility: Psychiatry Department of Widal Hospital
city: Paris
country: France
facility: EPS Maison Blanche
city: Pontoise
country: France
facility: Psychiatry Department of R. Dubos Hospital
Study officials:
References: