Rituximab for Schizophrenia Spectrum Disorder (RITS-PS-2019)

Rituximab - Immunotherapy for Schizophrenia Spectrum Disorder in Adults: An Open Pilot Study

This study evaluates the addition of rituximab to 12 patients diagnosed with treatment resistant schizophrenia spectrum disorder in an open trial.

Study Overview

• Status: Completed
• Conditions: Schizophrenia Spectrum and Other Psychotic Disorders; Treatment-resistant Schizophrenia
• Intervention / Treatment: Drug: Rituximab

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Örebro, Sweden, 70116
    • Region Örebro Län

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria (Swedish citizens):

1. patient ages 18 to 40 years
2. a duration of illness exceeding 2 years
3. correspond to "Markedly ill", "Severely ill" or "Among the most extremely ill patients" on the Clinical Global Impression - Severity scale (CGI-S)
4. Global Assessment of Functioning below 50
5. Schizophrenia spectrum disorder according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
6. treatment resistance, i.e. failing to remit despite adequate treatments
7. if female and with any risk for pregnancy, willing to use contraceptives
8. if antipsychotic treatment is prescribed the plasma concentrations of the drug must be tested and shown to be within therapeutic interval.
9. subjects should be judged by the investigator to be lucid and oriented to person, place, time, and situation when giving the informed consent.
10. immunoglobulin levels within the normal range

Exclusion Criteria:

1. on-going immunomodulatory treatment
2. pregnancy or breast-feeding
3. weight below 40 kg
4. clinically relevant on-going infection
5. chronic infections
6. positive screening test for hepatitis B, C, HIV or tuberculosis
7. any change of psychotropic medication within the previous 4 weeks
8. "much" or "very much improved" already at baseline according to CGI-I i.e. scores of 1 or 2 by the clinician
9. severe heart failure (NYHA grade IV) or other severe heart disease or history of cardiac arrhythmia or myocardial infarction
10. unable to make an informed decision to consent to the trial
11. in compulsory treatment
12. treatment with clozapine within the last 2 months
13. previous treatments with immunosuppressive agents
14. malignancy currently or within 2 years prior to inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	week 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	week 20
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".	week 20
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.	week 20
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).	week 20
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.	week 20
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.	week 20

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	week 40
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 40 will be measured.	week 40
Clinical Global Impression-Severity (CGI-S) scale	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".	week 40
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 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.	week 40
Changes in cognitive functioning	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.	week 20
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. 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.	week 40
B-cell subpopulations in relation to clinical response	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.	week 20
Life quality measured with Brunnsviken Brief Quality of Life Scale (BBQ)	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.	week 40
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).	week 40

Collaborators and Investigators

• Sponsor: Region Örebro County
• Collaborators: Örebro University, Sweden
• Investigators: Principal Investigator: Susanne Bejerot, Region Örebro Län

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2019
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): March 31, 2022

Study Registration Dates

• First Submitted: May 30, 2019
• First Submitted That Met QC Criteria: June 11, 2019
• First Posted (Actual): June 12, 2019

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: treatment-resistant; Immunopsychiatry; Schizophrenia spectrum disorder
• Additional Relevant MeSH Terms: Pathologic Processes; Schizophrenia; Disease; Psychotic Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: EudraCT Number: 2018-004618-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Details that can identify the patients will not be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No