Ocrelizumab for Psychosis by Autoimmunity

Официальное название

Ocrelizumab for Psychoses Possibly Caused by Synaptic Autoimmunity

Обзор

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.

Вмешательства

• Поведенческое Psychosis and cognitive assessments
  Administration of MINI, PANSS and Quality of Living scales
• Поведенческое Physical and neuro-cognitive evaluations
  Physical, neurological and cognitive evaluations.
• Диагностический тест Safety labs and electrocardiogram
  Metabolic panel, CBC and differential, urinalysis, ECG, recreational drugs. CD19+ B-cell count.
• Биопрепарат Ocrelizumab infusion
  Two IV infusions of 300 mg of ocrelizumab 2 weeks apart

Первичные конечные точки

• Score on the Positive and Negative Syndrome Scale (PANSS) [Срок оценки: Six months]

Вторичные конечные точки (3)

• Score on quality of life scales for psychiatric patients [Срок оценки: Six months]
• Score on NIH Cognitive Toolbox [Срок оценки: Six months]
• Antipsychotic-equivalent medication ordered by patient's psychiatrist [Срок оценки: Six months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Houston Methodist Research Institute — Houston

Публикации

• 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. PMID 27130657
• 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. PMID 28234799

Идентификаторы

NCT: NCT03971487 · Pro00021901

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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