Rituximab for Schizophrenia spectrum disorder

Inclusion criteria

• {"criterion_text":"- Age: 18 to 55 years"}
• {"criterion_text":"- Duration of psychiatric illness: exceeding 1 year"}
• {"criterion_text":"- Diagnosed with Schizophrenia spectrum disorder (SSD) according to Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5)"}
• {"criterion_text":"- If female and with any risk for pregnancy: willing to use contraceptives* or abstinence if normal and preferred lifestyle"}
• {"criterion_text":"- Subjects should be judged by the investigator to be lucid and oriented to person, place, time, and situation when giving the informed consent"}
• {"criterion_text":"- Insufficiently recovered from previous antipsychotic treatments"}
• {"criterion_text":"- A minimum score of 4 in CGI-Severity at baseline"}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- Positive and Negative Syndrome Scale (PANSS) is a measure for severity in patients with schizophrenia (Kay et al. 1987). It is widely used in the study of antipsychotic therapy and is known as the “gold standard” for the assessment of schizophrenia. To assess a patient using PANSS, an approximately 45-minute clinical interview is conducted. The patient is rated from 1 to 7 on 30 different symptoms based on the interview as well as reports from family members or caretaking healthcare workers...","definition_or_measurement_approach":"PANSS administered via ~45-minute clinical interview; 30 items each rated 1–7; total score used to assess severity and change from baseline."}
• {"endpoint_text":"- ... The time span considered is the week before the rating. Seven items measure “positive” symptoms, 7 items “negative” symptoms, and 16 items general psychopathology. Each item is graded between 1 and 7 resulting in a total score between 30 which correspond to no symptoms and a maximum of 210 points. We will evaluate the item A6 for depression separately at baseline and endpoints in order to assess depressive symptoms.","definition_or_measurement_approach":"PANSS scoring considers symptoms during the week before rating; subscales (positive/negative/general) and total score (30–210); item A6 analyzed separately for depressive symptoms."}

Secondary endpoints

• {"endpoint_text":"- Personal and Social Performance Scale (PSP) (Morosini et al., 2000) is a 100-point single-item rating scale, subdivided into 10 equal intervals. The ratings are based on the assessment of patient’s functioning in four main areas: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behaviors. In responders, we expect a 25 % reduction or more in the PSP score.","definition_or_measurement_approach":"PSP 0–100 single-item scale across four domains; response defined as ≥25% reduction from baseline."}
• {"endpoint_text":"- Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7-point Likert scale. CGI-I will also be administered to the next-of-kin. In both the clinical and next-of-kin assessment, clinical response in this study is regarded as a score of 1 or 2 corresponding to very much improved or much improved. Investigators may score CGI-I into half points, but those will be transformed into whole numbers in the analyses of the data.","definition_or_measurement_approach":"CGI-I 7-point scale; response = score of 1 or 2; assessments by clinician and next-of-kin; half points rounded to whole numbers for analysis."}
• {"endpoint_text":"- Clinical Global Impression-Severity scale (CGI-S) is a clinician rated measure of overall clinical severity in the context of the diagnostic group. A person with no clinical complaints or problems will get a score of 1. The score 7, which indicates the highest level of severity is phrased as “Among the most extremely ill patients”.","definition_or_measurement_approach":"CGI-S clinician-rated severity scale (1–7) used to assess change from baseline."}
• {"endpoint_text":"- Positive and Negative Syndrome Scale (PANSS) is a measure for severity in patients with schizophrenia. Improvements will be calculated by reducing the baseline scores with 30 points (which equals no symptoms) to reach a PANSS 0 score.","definition_or_measurement_approach":"Change in PANSS from baseline; improvements calculated relative to baseline using specified transformations (baseline minus 30 equals PANSS 0 reference)."}
• {"endpoint_text":"- VAS-health is a patient self-evaluated health measure using a horizontal visual analogue scale ranging from 0 (= worst imaginable health) to 100 (= best imaginable health) the day of the visit. A 25 % reduction from baseline will be regarded as a self-reported treatment response measure.","definition_or_measurement_approach":"Patient-reported VAS-health 0–100; response defined as ≥25% improvement from baseline."}
• {"endpoint_text":"- Patient’s Global Evaluation (PGE) provides a self-administered global measure of improvement on a 7-point Likert scale identical to the CGI-I scoring system. In this study minimal improvement, i.e. a score of 3 (or below) is regarded as treatment response as individuals with SSD frequently tend to lack ability to observe improvements.","definition_or_measurement_approach":"PGE self-rated 7-point scale; response defined as score ≤3 (minimal improvement or better)."}
• {"endpoint_text":"- Baseline levels of inflammatory markers in relation to treatment response (i.e. a PANSS reduction of 30% or more) will be examined at both endpoints. Change in inflammatory markers in relation to response will also be investigated. Severity and frequencies of adverse events according to Any Adverse Reactions-Revised (AAR-R).","definition_or_measurement_approach":"Laboratory inflammatory markers measured at baseline and endpoints; correlated with response (PANSS reduction ≥30%); adverse events recorded and graded using AAR-R."}
• {"endpoint_text":"- Severity and frequencies of adverse events according to Any Adverse Reactions-Revised (AAR-R).","definition_or_measurement_approach":"Safety endpoint: AEs summarized by severity and frequency per AAR-R."}
• {"endpoint_text":"- Change in brain activity (e.g. blood flow and Default mode network) and morphology before and after treatment and in relation to response.","definition_or_measurement_approach":"Neuroimaging (e.g., fMRI) measures of brain activity and morphology pre- and post-treatment; analyzed in relation to clinical response."}
• {"endpoint_text":"- Level 1 Cross-cutting symptom measure of global symptom severity (APA, 2013) is a patient rated measure included in the DSM-5, which assesses mental health domains that are important across psychiatric diagnoses. It includes 13 domains and each of the items are rated 0-4 on a Likert scale. We will investigate if each endorsed domain is associated with response.","definition_or_measurement_approach":"Patient-rated Level 1 cross-cutting measure (13 domains, items 0–4); association of endorsed domains with clinical response will be analyzed."}

Sweden

Earliest CTIS Part Ii Submission Date

04-03-2024

Latest Decision Or Authorization Date

11-12-2024

Processing Time Days

282

Number Of Sites

8

Number Of Participants

120

Primary sponsor

Full Name

Region Oerebro Laen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Sweden