Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits).
Clinical trials
Immunology
Inflammation
Magnetic resonance imaging
Monoclonal antibodies
Schizophrenia & psychotic disorders
Journal
BMC psychiatry
ISSN: 1471-244X
Titre abrégé: BMC Psychiatry
Pays: England
ID NLM: 100968559
Informations de publication
Date de publication:
23 10 2023
23 10 2023
Historique:
received:
22
09
2023
accepted:
03
10
2023
medline:
27
10
2023
pubmed:
24
10
2023
entrez:
23
10
2023
Statut:
epublish
Résumé
The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture. A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research. This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma. NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14
Sections du résumé
BACKGROUND
The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture.
METHODS
A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research.
DISCUSSION
This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma.
TRIAL REGISTRATION
NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14
Identifiants
pubmed: 37872497
doi: 10.1186/s12888-023-05250-5
pii: 10.1186/s12888-023-05250-5
pmc: PMC10594806
doi:
Substances chimiques
Rituximab
4F4X42SYQ6
Banques de données
ClinicalTrials.gov
['NCT05622201']
Types de publication
Clinical Trial Protocol
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
771Investigateurs
Peter Asellus
(P)
Lise Bergman-Nordgren
(L)
Simon Bylund
(S)
Jonas Eberhard
(J)
Clara Figueras Diaz
(C)
Karin Jacobson
(K)
Erica Lindeborg
(E)
Yvonne Lowert
(Y)
Erik Nordström
(E)
David Terstad Ollén
(D)
Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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