Clinical trial NCT05622201: A Randomized Controlled Trial With Rituximab for Psychotic Disorder in Adults
Official title: A Randomized Controlled Trial With Rituximab for Psychotic Disorder in Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Schizophrenia Spectrum and Other Psychotic Disorders
Keywords: RCT
immunomodulatory treatment
psychosis
rituximab
CD20 antibodies
Lead sponsor: Region Örebro County
Sponsor class: OTHER
First posted: 2022-11-18
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A proof-of-concept study: a multicenter, placebo-controlled, double-blinded, add-on intervention study
Primary purpose: TREATMENT

Brief summary: Immunological factors are assumed to be determinants for some psychiatric disorders, thus anti-inflammatory drugs may be helpful. However, studies on such treatments are scarce. An inflammatory modulating drug rituximab, cluster of differentiation antigen 20 antibodies (anti-CD20 antibodies), is a standard treatment for e.g. multiple sclerosis.

The investigators aim to test rituximab in a randomised placebo-controlled double-blinded, add-on treatment trial in 120 participants (18-55 years) with schizophrenia spectrum disorder. Sampling from blood for analyses of inflammatory mediators are investigated at gene and protein levels and resting state functional magnetic resonance imaging (rsfMRI) and lumbar puncture are optional. Biomarkers will be investigated in relation to treatment response.

Family member(s) to the patient and the patient (separate) will be asked to participate in a qualitative interview by an independent researcher after 3 months.

Detailed description: Immunological factors are assumed to be determinants for some psychiatric disorders, thus anti-inflammatory drugs may be helpful. However, studies on such treatments are scarce. Rituximab (anti-CD20 antibodies), a standard treatment for multiple sclerosis in Sweden, is an inflammatory modulating drug. In a small open pilot trial, markedly ill, treatment-resistant participants with schizophrenia spectrum disorder were treated with a single- dose rituximab (1000 mg), as add-on treatment to antipsychotics in Örebro, Sweden (2019-2022). Large improvements in all types of psychotic symptoms were evident, with long-lasting effects and few side-effects in most of the participants.

This is a proof-of-concept study based on our earlier findings. The investigators will conduct a multicenter, placebo-controlled, double-blinded, add-on intervention study for 120 participants with schizophrenia spectrum disorder (18-55 years). Sampling from blood for analyses of inflammatory mediators are investigated at gene and protein levels and rsfMRI and lumbar puncture are optional at baseline and endpoints. Biomarkers will be investigated in relation to treatment response.

Participants are assessed at five time-points; week 0, 2, 7, 12 (endpoint I) and 24 (endpoint II).

Research questions:

I Does the addition of rituximab to standard psychiatric treatment improve psychotic symptoms in SSD?

II Does overall disability improve with the addition of rituximab?

III Are clinical or biological markers related to treatment response?

IV Is rituximab safe and well tolerated by participants with SSD?

V Is rituximab effective for treatment resistant SSD?

In addition family member(s) to the patient will be asked to participate in a qualitative interview by a researcher after 3 months on changes in the patient's mood and anxiety level, general functioning, behaviours, energy level, psychotic symptoms, motivation, emotional reciprocity and insight to enable a qualitative analysis. We will also ask them about their general thoughts on the study. In addition we will interview the patient after 3 months using qualitative methods.

We also aim study changes in negative symptoms with the Motivation and pleasure- self report (MAP-SR) in addition to the Positive and Negative Syndrome Scale (PANSS) scale and Self-evaluation of Negative Symptoms (SNS). Childhood onset neuropsychiatric symptoms will be investigated retrospectively by the use of Five-to-Fifteen Brief (FTF-Brief).

Eligibility criteria: Inclusion Criteria:

1. ages 18 to 55 years
2. duration of illness exceeding 1 year
3. diagnosed with Schizophrenia spectrum disorder (SSD) according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
4. if female and with any risk for pregnancy, willing to use contraceptives or abstinence if normal and preferred lifestyle.
5. participants should be judged by the investigator to be lucid and oriented to person, place, time, and situation when giving the informed consent.
6. insufficiently recovered from previous antipsychotic treatments.
7. a minimum score of 4 (moderately ill) in Clinical global impression - severity (CGI-S) at baseline.

Exclusion Criteria:

1. pregnancy or breast-feeding
2. weight below 40 kg
3. clinically relevant ongoing infection at the discretion of the physician
4. chronic infections
5. positive test for hepatitis B, hepatitis C, HIV, or tuberculosis
6. malignancy currently or within 2 years prior to inclusion
7. current severe heart failure (NYHA grade IV) or any other severe heart disease (e.g. or history of cardiac arrhythmia or myocardial infarction)
8. any change of antipsychotic medication within the previous 4 weeks
9. unable to make an informed decision to consent to the trial
10. ongoing clozapine treatment
11. ongoing immunomodulatory treatment
12. treatments with monoclonal antibodies within 1 year before the inclusion

Primary outcomes:
measure: Proportion of responders to treatment, rated as much or very much improved with CGI-I
timeFrame: Baseline up to week 12
Secondary outcomes:
measure: Improvement in functioning
timeFrame: Baseline up to week 12 and 24
measure: Change in psychotic symptoms
timeFrame: Baseline up to 12 weeks
measure: Proportion of responders to treatment, rated as much or very much improved with CGI-I
timeFrame: Baseline up to week 24
measure: Improvement since baseline
timeFrame: Baseline up to week 12 and 24
measure: Change in severity since baseline
timeFrame: Baseline up to week 12 and 24
measure: Improvement in psychotic symptoms since baseline
timeFrame: Baseline up to week 24
measure: Change in self-rated overall health
timeFrame: Baseline up to week 12 and 24
measure: Patient-rated improvement
timeFrame: Baseline up to week 12 and 24
measure: Inflammatory markers in blood and/or cerebro spinal fluid (CSF)
timeFrame: Baseline up to week 12 and 24
measure: Safety and tolerability of rituximab
timeFrame: Baseline up to week 12 and 24
measure: fMRI
timeFrame: Baseline up to week 12 and 24
measure: Patient-rated change in psychiatric symptoms
timeFrame: Baseline up to week 12 and 24
Other outcomes:
measure: Depression
timeFrame: Baseline up to week 12 and 24
measure: Negative symptoms
timeFrame: Baseline week 12 and week 24
measure: Qualitative assessment
timeFrame: 12-18 weeks after infusion
Locations:
city: Örebro
country: Sweden
facility: Örebro university hospital
Study officials:
affiliation: Region Örebro län
name: Susanne Bejerot, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: