search
Back to results

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

Primary Purpose

Schizophrenia Spectrum and Other Psychotic Disorders

Status
Recruiting
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
Rituximab
Sponsored by
Region Örebro County
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia Spectrum and Other Psychotic Disorders focused on measuring RCT, immunomodulatory treatment, psychosis, rituximab, CD20 antibodies

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: ages 18 to 55 years duration of illness exceeding 1 year diagnosed with Schizophrenia spectrum disorder (SSD) according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). if female and with any risk for pregnancy, willing to use contraceptives or abstinence if normal and preferred lifestyle. participants should be judged by the investigator to be lucid and oriented to person, place, time, and situation when giving the informed consent. insufficiently recovered from previous antipsychotic treatments. a minimum score of 4 (moderately ill) in Clinical global impression - severity (CGI-S) at baseline. Exclusion Criteria: pregnancy or breast-feeding weight below 40 kg clinically relevant ongoing infection at the discretion of the physician chronic infections positive test for hepatitis B, hepatitis C, HIV, or tuberculosis malignancy currently or within 2 years prior to inclusion current severe heart failure (NYHA grade IV) or any other severe heart disease (e.g. or history of cardiac arrhythmia or myocardial infarction) any change of antipsychotic medication within the previous 4 weeks unable to make an informed decision to consent to the trial ongoing clozapine treatment ongoing immunomodulatory treatment treatments with monoclonal antibodies within 1 year before the inclusion

Sites / Locations

  • Örebro university hospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Rituximab

Placebo

Arm Description

Rituximab 1000 mg, infusion

Saline infusion

Outcomes

Primary Outcome Measures

Change in psychotic symptoms
Change in scores in the measure for psychotic symptoms "the Positive and Negative Syndrome Scale (PANSS)"

Secondary Outcome Measures

Improvement in functioning
Measuring overall disability with Personal and Social Performance Scale (PSP)
Proportion of responders to treatment, rated as much or very much improved with CGI-I
Improvement according to clinical rated Clinical Global Impression-Improvement (CGI-I)
Improvement since baseline
Improvement according to clinical rated Clinical Global Impression-Improvement (CGI-I)
Change in severity since baseline
Improvement according to clinical rated Clinical Global Impression-Severity (CGI-S)
Improvement in psychotic symptoms since baseline
Change in scores in the measure for psychotic symptoms "the Positive and Negative Syndrome Scale (PANSS)".
Change in self-rated overall health
Differences in patient self-rated health (VAS-health)
Patient-rated improvement
Patient's Global Evaluation of improvement (PGE) corresponding to the CGI-I scores
Inflammatory markers in blood and/or cerebro spinal fluid (CSF)
Baseline levels of inflammatory markers in relation to treatment response (optional)
Safety and tolerability of rituximab
Open questions and a questionnaire (AAR-Revised)
fMRI
Change in brain morphology and/or activity in fMRI (optional)
Patient-rated change in psychiatric symptoms
Mental health symptom domains (Level 1 Cross-cutting symptom measure of global symptom severity) in relationship to response.

Full Information

First Posted
November 14, 2022
Last Updated
October 9, 2023
Sponsor
Region Örebro County
search

1. Study Identification

Unique Protocol Identification Number
NCT05622201
Brief Title
A Randomized Controlled Trial With Rituximab for Psychotic Disorder in Adults
Acronym
RCT-RITS
Official Title
A Randomized Controlled Trial With Rituximab for Psychotic Disorder in Adults
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 21, 2023 (Actual)
Primary Completion Date
June 30, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Region Örebro County

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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? 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia Spectrum and Other Psychotic Disorders
Keywords
RCT, immunomodulatory treatment, psychosis, rituximab, CD20 antibodies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
A proof-of-concept study: a multicenter, placebo-controlled, double-blinded, add-on intervention study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Rituximab
Arm Type
Experimental
Arm Description
Rituximab 1000 mg, infusion
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Saline infusion
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Saline
Intervention Description
Infusion
Primary Outcome Measure Information:
Title
Change in psychotic symptoms
Description
Change in scores in the measure for psychotic symptoms "the Positive and Negative Syndrome Scale (PANSS)"
Time Frame
Baseline up to 12 weeks
Secondary Outcome Measure Information:
Title
Improvement in functioning
Description
Measuring overall disability with Personal and Social Performance Scale (PSP)
Time Frame
Baseline up to week 12 and 24
Title
Proportion of responders to treatment, rated as much or very much improved with CGI-I
Description
Improvement according to clinical rated Clinical Global Impression-Improvement (CGI-I)
Time Frame
Baseline up to week 12 and 24
Title
Improvement since baseline
Description
Improvement according to clinical rated Clinical Global Impression-Improvement (CGI-I)
Time Frame
Baseline up to week 12 and 24
Title
Change in severity since baseline
Description
Improvement according to clinical rated Clinical Global Impression-Severity (CGI-S)
Time Frame
Baseline up to week 12 and 24
Title
Improvement in psychotic symptoms since baseline
Description
Change in scores in the measure for psychotic symptoms "the Positive and Negative Syndrome Scale (PANSS)".
Time Frame
Baseline up to week 24
Title
Change in self-rated overall health
Description
Differences in patient self-rated health (VAS-health)
Time Frame
Baseline up to week 12 and 24
Title
Patient-rated improvement
Description
Patient's Global Evaluation of improvement (PGE) corresponding to the CGI-I scores
Time Frame
Baseline up to week 12 and 24
Title
Inflammatory markers in blood and/or cerebro spinal fluid (CSF)
Description
Baseline levels of inflammatory markers in relation to treatment response (optional)
Time Frame
Baseline up to week 12 and 24
Title
Safety and tolerability of rituximab
Description
Open questions and a questionnaire (AAR-Revised)
Time Frame
Baseline up to week 12 and 24
Title
fMRI
Description
Change in brain morphology and/or activity in fMRI (optional)
Time Frame
Baseline up to week 12 and 24
Title
Patient-rated change in psychiatric symptoms
Description
Mental health symptom domains (Level 1 Cross-cutting symptom measure of global symptom severity) in relationship to response.
Time Frame
Baseline up to week 12 and 24
Other Pre-specified Outcome Measures:
Title
Depression
Description
The depression item A6 in PANSS will be investigated separately
Time Frame
Baseline up to week 12 and 24
Title
Negative symptoms
Description
The Negative Syndrome Scale assessed by the clinician will be compared to self-rated negative symptoms measured with the Motivation and pleasure- self report (MAP-SR) in order to study how well they are correlated.
Time Frame
Baseline week 12 and week 24
Title
Qualitative assessment
Description
An informant will be interviewed on whether they can see changes in patients and patient will be interviewed separately on symptoms after 12 weeks
Time Frame
12-18 weeks after infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ages 18 to 55 years duration of illness exceeding 1 year diagnosed with Schizophrenia spectrum disorder (SSD) according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). if female and with any risk for pregnancy, willing to use contraceptives or abstinence if normal and preferred lifestyle. participants should be judged by the investigator to be lucid and oriented to person, place, time, and situation when giving the informed consent. insufficiently recovered from previous antipsychotic treatments. a minimum score of 4 (moderately ill) in Clinical global impression - severity (CGI-S) at baseline. Exclusion Criteria: pregnancy or breast-feeding weight below 40 kg clinically relevant ongoing infection at the discretion of the physician chronic infections positive test for hepatitis B, hepatitis C, HIV, or tuberculosis malignancy currently or within 2 years prior to inclusion current severe heart failure (NYHA grade IV) or any other severe heart disease (e.g. or history of cardiac arrhythmia or myocardial infarction) any change of antipsychotic medication within the previous 4 weeks unable to make an informed decision to consent to the trial ongoing clozapine treatment ongoing immunomodulatory treatment treatments with monoclonal antibodies within 1 year before the inclusion
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Susanne Bejerot, MD,PhD
Phone
0701655102
Ext
46
Email
susanne.bejerot@oru.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susanne Bejerot, MD, PhD
Organizational Affiliation
Region Örebro län
Official's Role
Principal Investigator
Facility Information:
Facility Name
Örebro university hospital
City
Örebro
ZIP/Postal Code
701 85
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susanne Bejerot, MD
Phone
0701655102
Email
susanne.bejerot@oru.se
First Name & Middle Initial & Last Name & Degree
Axel Nordenskjöld, MD
Phone
070-6049589
Email
axel.nordenskjold@oru.se

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Randomized Controlled Trial With Rituximab for Psychotic Disorder in Adults

We'll reach out to this number within 24 hrs