Back to resultsRituximab for Schizophrenia Spectrum Disorder (RITS-PS-2019)
Primary Purpose
Schizophrenia Spectrum and Other Psychotic Disorders, Treatment-resistant Schizophrenia
Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia Spectrum and Other Psychotic Disorders focused on measuring Immunopsychiatry, Schizophrenia spectrum disorder, treatment-resistant
Eligibility Criteria
Inclusion Criteria (Swedish citizens):
- patient ages 18 to 40 years
- a duration of illness exceeding 2 years
- correspond to "Markedly ill", "Severely ill" or "Among the most extremely ill patients" on the Clinical Global Impression - Severity scale (CGI-S)
- Global Assessment of Functioning below 50
- Schizophrenia spectrum disorder according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
- treatment resistance, i.e. failing to remit despite adequate treatments
- if female and with any risk for pregnancy, willing to use contraceptives
- if antipsychotic treatment is prescribed the plasma concentrations of the drug must be tested and shown to be within therapeutic interval.
- subjects should be judged by the investigator to be lucid and oriented to person, place, time, and situation when giving the informed consent.
- immunoglobulin levels within the normal range
Exclusion Criteria:
- on-going immunomodulatory treatment
- pregnancy or breast-feeding
- weight below 40 kg
- clinically relevant on-going infection
- chronic infections
- positive screening test for hepatitis B, C, HIV or tuberculosis
- any change of psychotropic medication within the previous 4 weeks
- "much" or "very much improved" already at baseline according to CGI-I i.e. scores of 1 or 2 by the clinician
- severe heart failure (NYHA grade IV) or other severe heart disease or history of cardiac arrhythmia or myocardial infarction
- unable to make an informed decision to consent to the trial
- in compulsory treatment
- treatment with clozapine within the last 2 months
- previous treatments with immunosuppressive agents
- malignancy currently or within 2 years prior to inclusion
Sites / Locations
- Region Örebro Län
Outcomes
Primary Outcome Measures
Positive and Negative Syndrome Scale (PANSS)
Change in symptoms measured as change in Positive and Negative Syndrome Scale (PANSS) score from baseline. PANSS measures symptom severity of patients with schizophrenia and is a clinically based interview. PANSS measures positive symptoms (7 items, range 7-49), which refer to e.g. hallucinations and delusions; negative symptoms (e.g. loss of normal functions) (7 items, range 1-7) and general disability (16 Items, range 16 -112) separately. Higher scores denote more symptoms and disability. PANSS total score range from 30-210. At least 40 % reduction in PANSS total score is regarded as response.
Secondary Outcome Measures
Personal and Social Performance Scale (PSP)
Personal and Social Performance Scale (PSP) gives a score for disability. The PSP is a 100-point single-item rating scale (range 1-100), subdivided into 10 equal intervals. Lower scores denote lower functioning. The ratings are based mainly on the assessment of patient's functioning in four main areas: 1) socially useful activities; 2) personal and social relationships; 3) self-care; and 4) disturbing and aggressive behaviours. Change in score between enrolment and week 20 will be measured.
Clinical Global Impression-Severity (CGI-S) scale
CGI-S is a clinician rated measure of overall clinical severity that is rated on a scale between 1 and 7. A person with no clinical complaints or problems will get a score of 1. The score 7 indicates the highest level of severity is phrased as "Among the most extremely ill patients".
Clinical Global Impression-Improvement (CGI-I) in relation to inflammatory markers
Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7 point Likert scale. A CGI-I score of 1 or 2 corresponds to be much or very much improved. Change in inflammatory markers in blood (gene expression and proteins) towards normality, in relation to clinical response will be measured.
Clinical Global Impression-Improvement (CGI-I). Proportion of responders.
Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7 point Likert scale. A CGI-I score of 1 or 2 corresponds to be much or very much improved. Three different informants base their CGI-I evaluations on independent assessments: a) The treating clinician, b) The patient's self-assessment and c) A next of kin. If the mean value of these three is below 2.5 then the patient will be regarded as a responder (representing much or very much improved since baseline).
Clinical Global Impression-Improvement (CGI-I).
Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7 point Likert scale. A CGI-I score of 1 or 2 corresponds to be much or very much improved. Three different informants base their CGI-I evaluations on independent assessments: a) The treating clinician, b) The patient's self-assessment and c) A next of kin. Range 3-21. A lower score depicts larger improvement.
Adverse event: Any Adverse Reactions (AAR). Safety and tolerability of rituximab
Any Adverse reactions (AAR) is a rating scale developed for this study and is not a validated questionnaire. It consists of a list of 26 symptoms. AAR maps adverse events related to rituximab treatment. These items are assessed for severity on a Likert scale (4 levels: none; mild; moderate; severe) and frequency (3 levels: occasionally; daily; several times daily). AAR is assessed by the clinician. An adverse event scale was required as an outcome measure by the Swedish Medical Products Agency.
Full Information
NCT ID
NCT03983018
First Posted
May 30, 2019
Last Updated
May 9, 2022
Sponsor
Region Örebro County
Collaborators
Örebro University, Sweden
1. Study Identification
Unique Protocol Identification Number
NCT03983018
Brief Title
Rituximab for Schizophrenia Spectrum Disorder (RITS-PS-2019)
Official Title
Rituximab - Immunotherapy for Schizophrenia Spectrum Disorder in Adults: An Open Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
August 7, 2019 (Actual)
Primary Completion Date
March 31, 2022 (Actual)
Study Completion Date
March 31, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Region Örebro County
Collaborators
Örebro University, Sweden
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study evaluates the addition of rituximab to 12 patients diagnosed with treatment resistant schizophrenia spectrum disorder in an open trial.
Detailed Description
Immunological factors may be determinants for some psychiatric disorders, thus immunomodulation may be helpful. Rituximab (antibodies against CD20, cluster of differentiation), a standard treatment for multiple sclerosis, is an anti-inflammatory drug, hitherto not tested for psychiatric disorders.
The aim of this study is to investigate whether the psychiatric symptoms of treatment-resistant adult psychiatric patients, diagnosed with schizophrenia spectrum disorder (SSD), are significantly improved after treatment with rituximab. Our purpose is to implement recent insights from "Immunopsychiatry" to find efficacious, but still tolerable treatment for these patients.
This is a single-site, 20-week, open pilot, add-on treatment as usual, trial, where the patients will be followed for 1 year.
Rituximab will be administered with one single dose of 1000 mg. Investigators will analyse inflammatory and metabolic biomarkers in relation to the primary outcome, treatment response (defined as clinically relevant reduction in the validated measure PANSS). Other outcomes are "much" or "very much improved" on Clinical Global Impression - Improvement scale (CGI-I) and change in Personal and Social Performance Scale measuring overall disability.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia Spectrum and Other Psychotic Disorders, Treatment-resistant Schizophrenia
Keywords
Immunopsychiatry, Schizophrenia spectrum disorder, treatment-resistant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
Outcomes Assessor
Masking Description
Each patient will be video recorded at base line, week 12, 20 and 40 in order to enable blinded assessment by an independent rater, and for the patient's own evaluation.
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Infusion
Primary Outcome Measure Information:
Title
Positive and Negative Syndrome Scale (PANSS)
Description
Change in symptoms measured as change in Positive and Negative Syndrome Scale (PANSS) score from baseline. PANSS measures symptom severity of patients with schizophrenia and is a clinically based interview. PANSS measures positive symptoms (7 items, range 7-49), which refer to e.g. hallucinations and delusions; negative symptoms (e.g. loss of normal functions) (7 items, range 1-7) and general disability (16 Items, range 16 -112) separately. Higher scores denote more symptoms and disability. PANSS total score range from 30-210. At least 40 % reduction in PANSS total score is regarded as response.
Time Frame
week 20
Secondary Outcome Measure Information:
Title
Personal and Social Performance Scale (PSP)
Description
Personal and Social Performance Scale (PSP) gives a score for disability. The PSP is a 100-point single-item rating scale (range 1-100), subdivided into 10 equal intervals. Lower scores denote lower functioning. The ratings are based mainly on the assessment of patient's functioning in four main areas: 1) socially useful activities; 2) personal and social relationships; 3) self-care; and 4) disturbing and aggressive behaviours. Change in score between enrolment and week 20 will be measured.
Time Frame
week 20
Title
Clinical Global Impression-Severity (CGI-S) scale
Description
CGI-S is a clinician rated measure of overall clinical severity that is rated on a scale between 1 and 7. A person with no clinical complaints or problems will get a score of 1. The score 7 indicates the highest level of severity is phrased as "Among the most extremely ill patients".
Time Frame
week 20
Title
Clinical Global Impression-Improvement (CGI-I) in relation to inflammatory markers
Description
Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7 point Likert scale. A CGI-I score of 1 or 2 corresponds to be much or very much improved. Change in inflammatory markers in blood (gene expression and proteins) towards normality, in relation to clinical response will be measured.
Time Frame
week 20
Title
Clinical Global Impression-Improvement (CGI-I). Proportion of responders.
Description
Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7 point Likert scale. A CGI-I score of 1 or 2 corresponds to be much or very much improved. Three different informants base their CGI-I evaluations on independent assessments: a) The treating clinician, b) The patient's self-assessment and c) A next of kin. If the mean value of these three is below 2.5 then the patient will be regarded as a responder (representing much or very much improved since baseline).
Time Frame
week 20
Title
Clinical Global Impression-Improvement (CGI-I).
Description
Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7 point Likert scale. A CGI-I score of 1 or 2 corresponds to be much or very much improved. Three different informants base their CGI-I evaluations on independent assessments: a) The treating clinician, b) The patient's self-assessment and c) A next of kin. Range 3-21. A lower score depicts larger improvement.
Time Frame
week 20
Title
Adverse event: Any Adverse Reactions (AAR). Safety and tolerability of rituximab
Description
Any Adverse reactions (AAR) is a rating scale developed for this study and is not a validated questionnaire. It consists of a list of 26 symptoms. AAR maps adverse events related to rituximab treatment. These items are assessed for severity on a Likert scale (4 levels: none; mild; moderate; severe) and frequency (3 levels: occasionally; daily; several times daily). AAR is assessed by the clinician. An adverse event scale was required as an outcome measure by the Swedish Medical Products Agency.
Time Frame
week 20
Other Pre-specified Outcome Measures:
Title
Positive and Negative Syndrome Scale (PANSS)
Description
Change in symptoms measured as change in Positive and Negative Syndrome Scale (PANSS) score from baseline. PANSS measures symptom severity of patients with schizophrenia and is a clinically based interview. PANSS measures positive symptoms (7 items, range 7-49), which refer to e.g. hallucinations and delusions; negative symptoms (e.g. loss of normal functions) (7 items, range 1-7) and general disability (16 Items, range 16 -112) separately. Higher scores denote more symptoms and disability. PANSS total score range from 30-210. At least 40 % reduction in PANSS total score is regarded as response.
Time Frame
week 40
Title
Personal and Social Performance Scale (PSP)
Description
Personal and Social Performance Scale (PSP) gives a score for disability. The PSP is a 100-point single-item rating scale (range 1-100), subdivided into 10 equal intervals. Lower scores denote lower functioning. The ratings are based mainly on the assessment of patient's functioning in four main areas: 1) socially useful activities; 2) personal and social relationships; 3) self-care; and 4) disturbing and aggressive behaviours. Change in score between enrolment and week 40 will be measured.
Time Frame
week 40
Title
Clinical Global Impression-Severity (CGI-S) scale
Description
Clinical Global Impression-Severity (CGI-S) scale is a clinician rated measure of overall clinical severity that is rated on a scale between 1 and 7. A person with no clinical complaints or problems will get a score of 1. The score 7 indicates the highest level of severity is phrased as "Among the most extremely ill patients".
Time Frame
week 40
Title
Clinical Global Impression-Improvement (CGI-I) in relation to inflammatory markers
Description
Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7 point Likert scale. A CGI-I score of 1 or 2 corresponds to be much or very much improved. Change in inflammatory markers in blood (gene expression and proteins) towards normality, in relationship to clinical response Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7 point Likert scale. A CGI-I score of 1 or 2 corresponds to be much or very much improved. Change in inflammatory markers in blood (gene expression and proteins) towards normality, in relation to clinical response (assessed by the clinician) will be measured.
Time Frame
week 40
Title
Changes in cognitive functioning
Description
The clinical assessment includes four sections of the Wechsler intelligence scales for adults (WAIS-IV); block design (range 1-19), letter number sequencing (range 1-19), digit symbol coding (range 1-19), and digit span (range 1-19). A full scale IQ of each participant will be estimated using the mean of the four scaled scores available and multiplying them by 11. A higher score denotes a cognitive improvement.
Time Frame
week 20
Title
Clinical Global Impression-Improvement (CGI-I).
Description
Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7 point Likert scale. A CGI-I score of 1 or 2 corresponds to be much or very much improved. Three different informants base their CGI-I evaluations on independent assessments: a) The treating clinician, b) The patient's self-assessment and c) A next of kin. If the mean value of these three is below 2.5 then the patient will be regarded as a responder (representing much or very much improved since baseline). Range 3-21. A lower score depicts larger improvement.
Time Frame
week 40
Title
B-cell subpopulations in relation to clinical response
Description
B-cell depletion at week 5, and B-cell subpopulations at week 20 in relation to clinical response (CGI-I) (assessed by the clinician) and baseline levels of B-cells.
Time Frame
week 20
Title
Life quality measured with Brunnsviken Brief Quality of Life Scale (BBQ)
Description
BBQ is a 12-item self-rated measurement of life satisfaction. BBQ is a Likert scale, range 0-48. Higher scores denote higher life satisfaction.
Time Frame
week 40
Title
Clinical Global Impression-Improvement (CGI-I). Proportion of responders.
Description
Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7 point Likert scale. A CGI-I score of 1 or 2 corresponds to be much or very much improved. Three different informants base their CGI-I evaluations on independent assessments: a) The treating clinician, b) The patient's self-assessment and c) A next of kin. If the mean value of these three is below 2.5 then the patient will be regarded as a responder (representing much or very much improved since baseline).
Time Frame
week 40
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria (Swedish citizens):
patient ages 18 to 40 years
a duration of illness exceeding 2 years
correspond to "Markedly ill", "Severely ill" or "Among the most extremely ill patients" on the Clinical Global Impression - Severity scale (CGI-S)
Global Assessment of Functioning below 50
Schizophrenia spectrum disorder according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
treatment resistance, i.e. failing to remit despite adequate treatments
if female and with any risk for pregnancy, willing to use contraceptives
if antipsychotic treatment is prescribed the plasma concentrations of the drug must be tested and shown to be within therapeutic interval.
subjects should be judged by the investigator to be lucid and oriented to person, place, time, and situation when giving the informed consent.
immunoglobulin levels within the normal range
Exclusion Criteria:
on-going immunomodulatory treatment
pregnancy or breast-feeding
weight below 40 kg
clinically relevant on-going infection
chronic infections
positive screening test for hepatitis B, C, HIV or tuberculosis
any change of psychotropic medication within the previous 4 weeks
"much" or "very much improved" already at baseline according to CGI-I i.e. scores of 1 or 2 by the clinician
severe heart failure (NYHA grade IV) or other severe heart disease or history of cardiac arrhythmia or myocardial infarction
unable to make an informed decision to consent to the trial
in compulsory treatment
treatment with clozapine within the last 2 months
previous treatments with immunosuppressive agents
malignancy currently or within 2 years prior to inclusion
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susanne Bejerot
Organizational Affiliation
Region Orebro lan
Official's Role
Principal Investigator
Facility Information:
Facility Name
Region Örebro Län
City
Örebro
ZIP/Postal Code
70116
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Details that can identify the patients will not be shared.
Learn more about this trial
Rituximab for Schizophrenia Spectrum Disorder (RITS-PS-2019)
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