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出境医 / 临床实验 / Ocrelizumab for Psychosis by Autoimmunity (OPA)

Ocrelizumab for Psychosis by Autoimmunity (OPA)

Study Description
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.

Condition or disease Intervention/treatment Phase
Schizo-Affective Type of Psychosis Schizophrenia Behavioral: Psychosis and cognitive assessments Behavioral: Physical and neuro-cognitive evaluations Diagnostic Test: Safety labs and electrocardiogram Biological: Ocrelizumab infusion Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized placebo-controlled therapeutic trial
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Ocrelizumab for Psychoses Possibly Caused by Synaptic Autoimmunity
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : September 2021
Arms and Interventions
Arm Intervention/treatment
Active Comparator: Ocrelizumab
Two doses of 300 mg of ocrelizumab will be administered as an intravenous infusion two weeks apart.
 Behavioral: Psychosis and cognitive assessments
Administration of MINI, PANSS and Quality of Living scales

Behavioral: Physical and neuro-cognitive evaluations
Physical, neurological and cognitive evaluations.

Diagnostic Test: Safety labs and electrocardiogram
Metabolic panel, CBC and differential, urinalysis, ECG, recreational drugs. CD19+ B-cell count.

Biological: Ocrelizumab infusion
Two IV infusions of 300 mg of ocrelizumab 2 weeks apart
Placebo Comparator: Placebo
Two placebo intravenous infusions will be administered two weeks apart.
 Behavioral: Psychosis and cognitive assessments
Administration of MINI, PANSS and Quality of Living scales

Behavioral: Physical and neuro-cognitive evaluations
Physical, neurological and cognitive evaluations.

Diagnostic Test: Safety labs and electrocardiogram
Metabolic panel, CBC and differential, urinalysis, ECG, recreational drugs. CD19+ B-cell count.
Outcome Measures
Primary Outcome Measures :
  1. Score on the Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Six months ]
    It measures symptoms of psychosis


Secondary Outcome Measures :
  1. Score on quality of life scales for psychiatric patients [ Time Frame: Six months ]
    (modified to include input by caregivers)

  2. Score on NIH Cognitive Toolbox [ Time Frame: Six months ]
    Tablet-implemented tool testing cognitive abilities, including working memory

  3. Antipsychotic-equivalent medication ordered by patient's psychiatrist [ Time Frame: Six months ]
    Dose of medications for psychosis transformed to a standard equivalent


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations

Contacts
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Contact: Joseph C Masdeu, MD, PhD 202-255-7899 jcmasdeu@houstonmethodist.org
Contact: Haroon Shahid, MD 713-441-1150 mhshahid@houstonmethodist.org

Locations
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United States, Texas
Houston Methodist Research Institute Recruiting
Houston, Texas, United States, 77030
Contact: Jennifer M Garrett, RN, CCRP    281-222-9983    jmgarrett@houstonmethodist.org   
Contact: Rejani Nair, RN, CCRP    713-441-1150 ext Masdeu    jcmasdeu@houstonmethodist.org   
Principal Investigator: Joseph C Masdeu, MD, PhD         
Sponsors and Collaborators
The Methodist Hospital System
Genentech, Inc.
Investigators
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Principal Investigator: Joseph C Masdeu, MD, PhD HOUSTON METHODIST NEUROLOGICAL INSTITUTE
Tracking Information
First Submitted Date  ICMJE May 30, 2019
First Posted Date  ICMJE June 3, 2019
Last Update Posted Date December 13, 2019
Actual Study Start Date  ICMJE October 1, 2019
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2019) 		Score on the Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Six months ]
It measures symptoms of psychosis
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2019)
  • Score on quality of life scales for psychiatric patients [ Time Frame: Six months ]
    (modified to include input by caregivers)
  • Score on NIH Cognitive Toolbox [ Time Frame: Six months ]
    Tablet-implemented tool testing cognitive abilities, including working memory
  • Antipsychotic-equivalent medication ordered by patient's psychiatrist [ Time Frame: Six months ]
    Dose of medications for psychosis transformed to a standard equivalent
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ocrelizumab for Psychosis by Autoimmunity
Official Title  ICMJE Ocrelizumab for Psychoses Possibly Caused by Synaptic Autoimmunity
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized placebo-controlled therapeutic trial
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Schizo-Affective Type of Psychosis
  • Schizophrenia
Intervention  ICMJE
  • Behavioral: Psychosis and cognitive assessments
    Administration of MINI, PANSS and Quality of Living scales
  • Behavioral: Physical and neuro-cognitive evaluations
    Physical, neurological and cognitive evaluations.
  • Diagnostic Test: Safety labs and electrocardiogram
    Metabolic panel, CBC and differential, urinalysis, ECG, recreational drugs. CD19+ B-cell count.
  • Biological: Ocrelizumab infusion
    Two IV infusions of 300 mg of ocrelizumab 2 weeks apart
Study Arms  ICMJE
  • Active Comparator: Ocrelizumab
    Two doses of 300 mg of ocrelizumab will be administered as an intravenous infusion two weeks apart.
    Interventions:
    • Behavioral: Psychosis and cognitive assessments
    • Behavioral: Physical and neuro-cognitive evaluations
    • Diagnostic Test: Safety labs and electrocardiogram
    • Biological: Ocrelizumab infusion
  • Placebo Comparator: Placebo
    Two placebo intravenous infusions will be administered two weeks apart.
    Interventions:
    • Behavioral: Psychosis and cognitive assessments
    • Behavioral: Physical and neuro-cognitive evaluations
    • Diagnostic Test: Safety labs and electrocardiogram
Publications *
  • 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. Review.
  • 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. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 30, 2019) 		40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2021
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 35 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Joseph C Masdeu, MD, PhD 202-255-7899 jcmasdeu@houstonmethodist.org
Contact: Haroon Shahid, MD 713-441-1150 mhshahid@houstonmethodist.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03971487
Other Study ID Numbers  ICMJE Pro00021901
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: It is possible that anonymized data could be shared with other researchers at the conclusion of the study.
Responsible Party The Methodist Hospital System
Study Sponsor  ICMJE The Methodist Hospital System
Collaborators  ICMJE Genentech, Inc.
Investigators  ICMJE
Principal Investigator: Joseph C Masdeu, MD, PhD HOUSTON METHODIST NEUROLOGICAL INSTITUTE
PRS Account The Methodist Hospital System
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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