A Randomized Controlled Trial With Rituximab for Psychotic Disorder in Adults

NCT ID: NCT05622201

Last Updated: 2024-12-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-21
• Study Completion Date: 2026-12-31

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).

Conditions

Schizophrenia Spectrum and Other Psychotic Disorders

Keywords

RCT; immunomodulatory treatment; psychosis; rituximab; CD20 antibodies

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Rituximab

Rituximab 1000 mg, infusion

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

Infusion

Placebo

Saline infusion

Group Type: PLACEBO_COMPARATOR

Rituximab

Intervention Type: DRUG

Infusion

Interventions

Rituximab

Infusion

Intervention Type: DRUG

Other Intervention Names

Saline

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Region Örebro County

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susanne Bejerot, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Region Örebro län

Locations

Örebro university hospital

Örebro, , Sweden

Site Status: RECRUITING

Countries

Sweden

Central Contacts

Susanne Bejerot, MD,PhD

Role: CONTACT

Phone: 0701655102

Email: susanne.bejerot@oru.se

Facility Contacts

Susanne Bejerot, MD

Role: primary

Axel Nordenskjöld, MD

Role: backup

References

Bejerot S, Eklund D, Hesser H, Hietala MA, Kariis T, Lange N, Lebedev A, Montgomery S, Nordenskjold A, Petrovic P, Soderbergh A, Thunberg P, Wikstrom S, Humble MB; RCT-Rits study collaboration group. Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits). BMC Psychiatry. 2023 Oct 23;23(1):771. doi: 10.1186/s12888-023-05250-5.

Reference Type: DERIVED

PMID: 37872497 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

278825

Identifier Type: -

Identifier Source: org_study_id