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

Phase 1

Completed

• Conditions: Treatment-resistant Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders

• Registration Number: NCT03983018
• Lead Sponsor: Region Örebro County

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-05-30
• Study First Submitted QC: 2019-06-11
• Study First Posted: 2019-06-12
• Study Start: 2019-08-07
• Primary Completion: 2022-03-31
• Study Completion: 2022-03-31
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-09
• Last Update Posted: 2022-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

Not provided

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Positive and Negative Syndrome Scale (PANSS)	week 20	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

Name	Time	Method
Personal and Social Performance Scale (PSP)	week 20	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-Improvement (CGI-I). Proportion of responders.	week 20	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-Severity (CGI-S) scale	week 20	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	week 20	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).	week 20	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	week 20	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.

Trial Locations

Locations (1)

Region Örebro Län; 🇸🇪 Örebro, Sweden