A Randomized Controlled Trial With Rituximab for Psychotic Disorder in Adults (RCT-RITS)

Region Örebro County

Status and phase: Enrolling; Phase 2

Conditions: Schizophrenia Spectrum and Other Psychotic Disorders

Treatments: Drug: Rituximab

Study type: Interventional

Funder types: Other

Identifiers

NCT05622201

278825

Details and patient eligibility

About

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.

Full 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).

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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120 participants in 2 patient groups, including a placebo group

Rituximab

Experimental group

Description:

Rituximab 1000 mg, infusion

Treatment:

Drug: Rituximab

Placebo

Placebo Comparator group

Description:

Saline infusion

Treatment:

Drug: Rituximab