Treatment-resistant patients with schizophrenia spectrum disorder (SSD)
Conditions
Sponsors
Region Örebro län
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age: 18 to 40 years 2) Duration of psychiatric illness: exceeding 2 years 3) Rated “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) Current diagnosis according to Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5) of SSD (schizophrenia spectrum disorder) 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 the 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether severely ill, treatment resistant, psychiatric patients with schizophrenia spectrum disorder (SSD) are significantly improved after treatment with the immunomodulatory drug rituximab (anti-CD20 antibodies) compared to baseline.;Secondary Objective: - To examine whether baseline levels of inflammatory markers predict treatment response. - To examine whether changes in inflammatory markers and B-cell depletion correlate with treatment response. - To examine metabolic mediators prior and after treatment and if they correlate with treatment response. - To examine whether there is a change in gut permeability after treatment. - To examine whether there is a change in cognition after treatment. - To investigate if there is a change in brain activity after treatment. - To investigate the patients’ experiences of the novel treatment with a qualitative content analysis. - To assess safety and tolerability of rituximab during treatment for SSD ;Primary end point(s): The primary outcome measure is change in symptoms measured as change in PANSS score. ;Timepoint(s) of evaluation of this end point: Week 20, 40 and 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Global improvement at week 20, according to a balanced assessment (mean value of three independent assessors: 1) The treating clinician, 2) The patient’s self-assessment and 3) A next-of-kin) using the Clinical Global Impression-Improvement (CGI-I) scale (range 1-7; 1 representing “Very much improved”). • Change in Personal and Social Performance Scale (PCP) measuring overall disability • Change from baseline up to week 20 of illness severity (CGI-S) assessed by the clinician • Difference from baseline up to week 20 in inflammatory markers in blood (gene expression and proteins) in relationship to clinical response (CGI-I) • Proportion of responders to treatment, i.e. rated as much or very much improved since baseline according to CGI-I assessed by three different informants: 1) The treating clinician, 2) The patient’s self-assessment and 3) 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). • Safety and tolerability of rituximab during treatment for SSD measured with the questionnaire Any Adverse Reactions (AAR). ;Timepoint(s) of evaluation of this end point: Week 20, 40 and 52 | — |
Countries
Sweden
Contacts
Public ContactPsykiatriska kliniken USÖ
Region Örebro län
Outcome results
None listed