Clinical trial NCT03983018: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia Spectrum and Other Psychotic Disorders
Treatment-resistant Schizophrenia
Keywords: Immunopsychiatry
Schizophrenia spectrum disorder
treatment-resistant
Lead sponsor: Region Örebro County
Sponsor class: OTHER
Collaborators: name: Örebro University, Sweden
First posted: 2019-06-12
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Positive and Negative Syndrome Scale (PANSS)
timeFrame: week 20
Secondary outcomes:
measure: Personal and Social Performance Scale (PSP)
timeFrame: week 20
measure: Clinical Global Impression-Severity (CGI-S) Scale
timeFrame: week 20
measure: Clinical Global Impression-Improvement (CGI-I) in Relation to Inflammatory Markers
timeFrame: week 20
measure: Clinical Global Impression-Improvement (CGI-I). Proportion of Responders.
timeFrame: week 20
measure: Clinical Global Impression-Improvement (CGI-I).
timeFrame: week 20
measure: Adverse Event: Any Adverse Reactions (AAR). Safety and Tolerability of Rituximab
timeFrame: week 20
Other outcomes:
measure: Positive and Negative Syndrome Scale (PANSS)
timeFrame: week 40
measure: Personal and Social Performance Scale (PSP)
timeFrame: week 40
measure: Clinical Global Impression-Severity (CGI-S) Scale
timeFrame: week 40
measure: Clinical Global Impression-Improvement (CGI-I) in Relation to Inflammatory Markers
timeFrame: week 40
measure: Changes in Cognitive Functioning
timeFrame: week 20
measure: Clinical Global Impression-Improvement (CGI-I).
timeFrame: week 40
measure: B-cell Subpopulations in Relation to Clinical Response
timeFrame: week 20
measure: Life Quality Measured With Brunnsviken Brief Quality of Life Scale (BBQ)
timeFrame: week 40
measure: Clinical Global Impression-Improvement (CGI-I). Proportion of Responders.
timeFrame: week 40
Locations:
city: Örebro
country: Sweden
facility: Region Örebro Län
Study officials:
affiliation: Region Orebro lan
name: Susanne Bejerot
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bejerot S, Sigra Stein S, Welin E, Eklund D, Hylen U, Humble MB. Rituximab as an adjunctive treatment for schizophrenia spectrum disorder or obsessive-compulsive disorder: Two open-label pilot studies on treatment-resistant patients. J Psychiatr Res. 2023 Feb;158:319-329. doi: 10.1016/j.jpsychires.2022.12.003. Epub 2022 Dec 20.
citation: Thunberg P, Fresnais D, Hamilton P, Bejerot S, Humble MB. Immunomodulatory treatment may change functional and structural brain imaging in severe mental disorders. Brain Behav Immun Health. 2024 Sep 16;41:100864. doi: 10.1016/j.bbih.2024.100864. eCollection 2024 Nov.