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

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ClinicalTrials.gov Identifier: NCT03983018
Recruitment Status : Recruiting
First Posted : June 12, 2019
Last Update Posted : August 12, 2019
Sponsor:
Collaborator:
Örebro University
Information provided by (Responsible Party):
Susanne Bejerot, Region Örebro County

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

Condition or disease Intervention/treatment Phase
Schizophrenia Spectrum and Other Psychotic Disorders Treatment-resistant Schizophrenia Drug: Rituximab Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Masking Description: Each patient will be video recorded at base line, week 12, 20 and 40 in order to enable blinded assessment by an independent rater, and for the patient's own evaluation.
Primary Purpose: Treatment
Official Title: Rituximab - Immunotherapy for Schizophrenia Spectrum Disorder in Adults: An Open Pilot Study
Actual Study Start Date : August 7, 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
Drug Information available for: Rituximab


Intervention Details:
  • Drug: Rituximab
    Infusion


Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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.

  2. 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".

  3. 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.

  4. 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).

  5. 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.

  6. 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.


Other Outcome Measures:
  1. Positive and Negative Syndrome Scale (PANSS) [ Time Frame: week 40 ]
    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.

  2. Personal and Social Performance Scale (PSP) [ Time Frame: week 40 ]
    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 40 will be measured.

  3. Clinical Global Impression-Severity (CGI-S) scale [ Time Frame: week 40 ]
    Clinical Global Impression-Severity (CGI-S) scale 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".

  4. Clinical Global Impression-Improvement (CGI-I) in relation to inflammatory markers [ Time Frame: week 40 ]
    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 relationship to clinical response 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 (assessed by the clinician) will be measured.

  5. Changes in cognitive functioning [ Time Frame: week 20 ]
    The clinical assessment includes four sections of the Wechsler intelligence scales for adults (WAIS-IV); block design (range 1-19), letter number sequencing (range 1-19), digit symbol coding (range 1-19), and digit span (range 1-19). A full scale IQ of each participant will be estimated using the mean of the four scaled scores available and multiplying them by 11. A higher score denotes a cognitive improvement.

  6. Clinical Global Impression-Improvement (CGI-I). [ Time Frame: week 40 ]
    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). Range 3-21. A lower score depicts larger improvement.

  7. B-cell subpopulations in relation to clinical response [ Time Frame: week 20 ]
    B-cell depletion at week 5, and B-cell subpopulations at week 20 in relation to clinical response (CGI-I) (assessed by the clinician) and baseline levels of B-cells.

  8. Life quality measured with Brunnsviken Brief Quality of Life Scale (BBQ) [ Time Frame: week 40 ]
    BBQ is a 12-item self-rated measurement of life satisfaction. BBQ is a Likert scale, range 0-48. Higher scores denote higher life satisfaction.

  9. Clinical Global Impression-Improvement (CGI-I). Proportion of responders. [ Time Frame: week 40 ]
    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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03983018


Contacts
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Contact: Susanne Bejerot (0)70 1655102 ext +46 susanne.bejerot@oru.se
Contact: Ulrika Hylén, nurse ulrika.hylen@regionorebrolan.se

Locations
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Sweden
Region Örebro Län Recruiting
Örebro, Sweden, 70116
Contact: Susanne Bejerot, MD         
Contact: Ulrika Hylen       ulrika.hylen@regionorebrolan.se   
Sub-Investigator: Daniel Eklund, PhD         
Sub-Investigator: Eva Särndahl, PhD         
Sub-Investigator: Sofia Sigra, PhD student         
Sub-Investigator: Eva Hesselmark, PhD         
Sub-Investigator: Mats Humble, PhD         
Sponsors and Collaborators
Region Örebro County
Örebro University
Investigators
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Principal Investigator: Susanne Bejerot Region Orebro lan

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Responsible Party: Susanne Bejerot, Professor, Region Örebro County
ClinicalTrials.gov Identifier: NCT03983018     History of Changes
Other Study ID Numbers: EudraCT Number: 2018-004618-17
First Posted: June 12, 2019    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Details that can identify the patients will not be shared.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Susanne Bejerot, Region Örebro County:
Immunopsychiatry
Schizophrenia spectrum disorder
treatment-resistant
Additional relevant MeSH terms:
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Disease
Schizophrenia
Mental Disorders
Psychotic Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Pathologic Processes
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents