Rituximab for Schizophrenia Spectrum Disorder (RITS-PS-2019)

Overview

This study evaluates the addition of rituximab to 12 patients diagnosed with treatment resistant schizophrenia spectrum disorder in an open trial.

Full Title of Study: “Rituximab – Immunotherapy for Schizophrenia Spectrum Disorder in Adults: An Open Pilot Study”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: June 2021

Detailed Description

Immunological factors may be determinants for some psychiatric disorders, thus immunomodulation may be helpful. Rituximab (antibodies against CD20, cluster of differentiation), a standard treatment for multiple sclerosis, is an anti-inflammatory drug, hitherto not tested for psychiatric disorders.

The aim of this study is to investigate whether the psychiatric symptoms of treatment-resistant adult psychiatric patients, diagnosed with schizophrenia spectrum disorder (SSD), are significantly improved after treatment with rituximab. Our purpose is to implement recent insights from "Immunopsychiatry" to find efficacious, but still tolerable treatment for these patients.

This is a single-site, 20-week, open pilot, add-on treatment as usual, trial, where the patients will be followed for 1 year.

Rituximab will be administered with one single dose of 1000 mg. Investigators will analyse inflammatory and metabolic biomarkers in relation to the primary outcome, treatment response (defined as clinically relevant reduction in the validated measure PANSS). Other outcomes are "much" or "very much improved" on Clinical Global Impression – Improvement scale (CGI-I) and change in Personal and Social Performance Scale measuring overall disability.

Interventions

  • Drug: Rituximab
    • Infusion

Clinical Trial Outcome Measures

Primary Measures

  • Positive and Negative Syndrome Scale (PANSS)
    • Time Frame: week 20
    • Change in symptoms measured as change in Positive and Negative Syndrome Scale (PANSS) score from baseline. PANSS measures symptom severity of patients with schizophrenia and is a clinically based interview. PANSS measures positive symptoms (7 items, range 7-49), which refer to e.g. hallucinations and delusions; negative symptoms (e.g. loss of normal functions) (7 items, range 1-7) and general disability (16 Items, range 16 -112) separately. Higher scores denote more symptoms and disability. PANSS total score range from 30-210. At least 40 % reduction in PANSS total score is regarded as response.

Secondary Measures

  • Personal and Social Performance Scale (PSP)
    • Time Frame: week 20
    • Personal and Social Performance Scale (PSP) gives a score for disability. The PSP is a 100-point single-item rating scale (range 1-100), subdivided into 10 equal intervals. Lower scores denote lower functioning. The ratings are based mainly 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 behaviours. Change in score between enrolment and week 20 will be measured.
  • Clinical Global Impression-Severity (CGI-S) scale
    • Time Frame: week 20
    • CGI-S is a clinician rated measure of overall clinical severity that is rated on a scale between 1 and 7. A person with no clinical complaints or problems will get a score of 1. The score 7 indicates the highest level of severity is phrased as “Among the most extremely ill patients”.
  • Clinical Global Impression-Improvement (CGI-I) in relation to inflammatory markers
    • Time Frame: week 20
    • Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7 point Likert scale. A CGI-I score of 1 or 2 corresponds to be much or very much improved. Change in inflammatory markers in blood (gene expression and proteins) towards normality, in relation to clinical response will be measured.
  • Clinical Global Impression-Improvement (CGI-I). Proportion of responders.
    • Time Frame: week 20
    • Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7 point Likert scale. A CGI-I score of 1 or 2 corresponds to be much or very much improved. Three different informants base their CGI-I evaluations on independent assessments: a) The treating clinician, b) The patient’s self-assessment and c) A next of kin. If the mean value of these three is below 2.5 then the patient will be regarded as a responder (representing much or very much improved since baseline).
  • Clinical Global Impression-Improvement (CGI-I).
    • Time Frame: week 20
    • Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7 point Likert scale. A CGI-I score of 1 or 2 corresponds to be much or very much improved. Three different informants base their CGI-I evaluations on independent assessments: a) The treating clinician, b) The patient’s self-assessment and c) A next of kin. Range 3-21. A lower score depicts larger improvement.
  • Adverse event: Any Adverse Reactions (AAR). Safety and tolerability of rituximab
    • Time Frame: week 20
    • Any Adverse reactions (AAR) is a rating scale developed for this study and is not a validated questionnaire. It consists of a list of 26 symptoms. AAR maps adverse events related to rituximab treatment. These items are assessed for severity on a Likert scale (4 levels: none; mild; moderate; severe) and frequency (3 levels: occasionally; daily; several times daily). AAR is assessed by the clinician. An adverse event scale was required as an outcome measure by the Swedish Medical Products Agency.

Participating in This Clinical Trial

Inclusion Criteria (Swedish citizens):

1. patient ages 18 to 40 years

2. a duration of illness exceeding 2 years

3. correspond to "Markedly ill", "Severely ill" or "Among the most extremely ill patients" on the Clinical Global Impression – Severity scale (CGI-S)

4. Global Assessment of Functioning below 50

5. Schizophrenia spectrum disorder according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).

6. treatment resistance, i.e. failing to remit despite adequate treatments

7. if female and with any risk for pregnancy, willing to use contraceptives

8. if antipsychotic treatment is prescribed the plasma concentrations of the drug must be tested and shown to be within therapeutic interval.

9. subjects should be judged by the investigator to be lucid and oriented to person, place, time, and situation when giving the informed consent.

10. immunoglobulin levels within the normal range

Exclusion Criteria

1. on-going immunomodulatory treatment

2. pregnancy or breast-feeding

3. weight below 40 kg

4. clinically relevant on-going infection

5. chronic infections

6. positive screening test for hepatitis B, C, HIV or tuberculosis

7. any change of psychotropic medication within the previous 4 weeks

8. "much" or "very much improved" already at baseline according to CGI-I i.e. scores of 1 or 2 by the clinician

9. severe heart failure (NYHA grade IV) or other severe heart disease or history of cardiac arrhythmia or myocardial infarction

10. unable to make an informed decision to consent to the trial

11. in compulsory treatment

12. treatment with clozapine within the last 2 months

13. previous treatments with immunosuppressive agents

14. malignancy currently or within 2 years prior to inclusion

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 40 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Region Örebro County
  • Collaborator
    • Örebro University, Sweden
  • Provider of Information About this Clinical Study
    • Principal Investigator: Susanne Bejerot, Professor – Region Örebro County
  • Overall Official(s)
    • Susanne Bejerot, Principal Investigator, Region Orebro lan
  • Overall Contact(s)
    • Susanne Bejerot, (0)70 1655102, susanne.bejerot@oru.se

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