Ocrelizumab for Psychosis by Autoimmunity

Study Overview
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Brief Summary
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Some people who have what doctors currently call schizophrenia or bipolar disease may actually have a brain disease caused by auto-antibodies. Auto-antibodies are produced when the normal defense mechanism of the body goes wrong and begins to attack the body, similar to friendly fire. Auto-antibodies attack brain receptors and then the person who has this problem begins to have hallucinations and other manifestations of schizophrenia, like feeling that people can see what they are thinking and also feeling that other people do not like them. If this disease is caused by auto-antibodies, typically the person is well until they are 15 years of age or older, but seldom older than 35 years. Then, in a matter of a few months they begin to have hallucinations and the other symptoms. Doctors still do not know whether some people with schizophrenia or bipolar disease have auto-antibodies attacking their brain. For this reason, in this study some of these patients will receive a treatment that suppresses the auto-antibodies and their symptoms after treatment will be compared with the symptoms of a group of similar patients who are given a preparation that looks like the real treatment, but it is not.

Official Title
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Ocrelizumab for Psychoses Possibly Caused by Synaptic Autoimmunity

Conditions
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Schizo-Affective Type of Psychosis, Schizophrenia

Intervention / Treatment
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* Behavioral: Psychosis and cognitive assessments
* Behavioral: Physical and neuro-cognitive evaluations
* Diagnostic Test: Safety labs and electrocardiogram
* Biological: Ocrelizumab infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals of either sex, 18-35 years of age. Having an active psychotic disorder meeting DSM-5 criteria, including a duration of at least six months, for Schizophrenia Spectrum Disorder, as defined by the Mini International Neuropsychiatric Interview (MINI). A total PANSS ≥ 60 and a score ≥ 4 on at least 2 of the PANSS positive symptoms. Normal academic performance at least until the age of 15 years and absence of psychiatric symptoms before the same age. Ability to assent or consent to the performance of the study and participate in testing procedures. Exclusion Criteria: The dose of antipsychotic medication (if they are on one) has been changed less than two weeks prior to baseline PANSS testing (Visit 2, see below). Patient treated with a medication designed to suppress the immune system, other than standard analgesics or antipyretics, in the six months prior to randomization. Vaccinated with a live-attenuated vaccine less than 4 weeks before ocrelizumab infusion or with a non-live vaccine less than 2 weeks before infusion. Active infection, or history of or known presence of recurrent or chronic infection (for example, hepatitis B or C, Human Immunodeficiency Virus, syphilis, tuberculosis, PML). History of brain tumor, stroke, severe head trauma or multiple sclerosis. Active cancer, metabolic encephalopathy, severe cardiovascular or renal disease. In the judgment of the PI, psychosis related to substance abuse or metabolic disorders. Pregnancy or lactation. Requirement for chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study. History of or currently active primary or secondary immunodeficiency. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Contraindications to or intolerance of oral or IV corticosteroids.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized placebo-controlled therapeutic trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ocrelizumab<br>Two doses of 300 mg of ocrelizumab will be administered as an intravenous infusion two weeks apart. | Behavioral: Psychosis and cognitive assessments<br>* Administration of MINI, PANSS and Quality of Living scales<br>Behavioral: Physical and neuro-cognitive evaluations<br>* Physical, neurological and cognitive evaluations.<br>Diagnostic Test: Safety labs and electrocardiogram<br>* Metabolic panel, CBC and differential, urinalysis, ECG, recreational drugs. CD19+ B-cell count.<br>Biological: Ocrelizumab infusion<br>* Two IV infusions of 300 mg of ocrelizumab 2 weeks apart<br>|
| Placebo Comparator: Placebo<br>Two placebo intravenous infusions will be administered two weeks apart. | Behavioral: Psychosis and cognitive assessments<br>* Administration of MINI, PANSS and Quality of Living scales<br>Behavioral: Physical and neuro-cognitive evaluations<br>* Physical, neurological and cognitive evaluations.<br>Diagnostic Test: Safety labs and electrocardiogram<br>* Metabolic panel, CBC and differential, urinalysis, ECG, recreational drugs. CD19+ B-cell count.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score on the Positive and Negative Syndrome Scale (PANSS) | It measures symptoms of psychosis | Six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score on quality of life scales for psychiatric patients | (modified to include input by caregivers) | Six months | 
| Score on NIH Cognitive Toolbox | Tablet-implemented tool testing cognitive abilities, including working memory | Six months | 
| Antipsychotic-equivalent medication ordered by patient's psychiatrist | Dose of medications for psychosis transformed to a standard equivalent | Six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizo-affective psychosis, schizophrenia