Clinical trial NCT03971487: Ocrelizumab for Psychosis by Autoimmunity
Official title: Ocrelizumab for Psychoses Possibly Caused by Synaptic Autoimmunity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Schizo-Affective Type of Psychosis
Schizophrenia
Keywords: schizo-affective psychosis
schizophrenia
Lead sponsor: The Methodist Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2019-06-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized placebo-controlled therapeutic trial
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Score on the Positive and Negative Syndrome Scale (PANSS)
timeFrame: Six months
Secondary outcomes:
measure: Score on quality of life scales for psychiatric patients
timeFrame: Six months
measure: Score on NIH Cognitive Toolbox
timeFrame: Six months
measure: Antipsychotic-equivalent medication ordered by patient's psychiatrist
timeFrame: Six months
Other outcomes:
Locations:
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
Study officials:
affiliation: HOUSTON METHODIST NEUROLOGICAL INSTITUTE
name: Joseph C Masdeu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Masdeu JC, Dalmau J, Berman KF. NMDA Receptor Internalization by Autoantibodies: A Reversible Mechanism Underlying Psychosis? Trends Neurosci. 2016 May;39(5):300-310. doi: 10.1016/j.tins.2016.02.006. Epub 2016 Apr 26.
citation: Masdeu JC. Detecting synaptic autoantibodies in psychoses: need for more sensitive methods. Curr Opin Neurol. 2017 Jun;30(3):317-326. doi: 10.1097/WCO.0000000000000447.