Rituximab for Obsessive-compulsive Disorder. (RITS-PO-2019)

Rituximab - Immunotherapy for Obsessive-compulsive Disorder: An Open Pilot Study

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

Study Overview

• Status: Completed
• Conditions: Obsessive-Compulsive Disorder; Treatment Resistant Disorders
• Intervention / Treatment: Drug: Rituximab

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 obsessive-compulsive disorder (OCD), are significantly improved after treatment with rituximab. The investigator's 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 Y-BOCS). 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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Örebro, Sweden, 70116
    • Region Örebro Län
  • Örebro, Sweden, 70356
    • Region Örebro Län

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 (GAF) below 50.
5. obsessive-compulsive 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 psychotropic 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.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: SINGLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yale-Brown obsessive- compulsive scale (Y-BOCS)	Y-BOCS maps symptoms and measures severity of obsessive-compulsive symptoms by a clinician. Y-BOCS has a range between 0 and 40 points, higher scores denotes worse symptoms. Outcome is measured as change in Y-BOCS score from baseline. At least 35% reduction in the score since baseline is defined as a response.	week 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Personal and Social Performance Scale (PSP)	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.	week 20
Clinical Global Impression-Improvement (CGI-I). Proportion of responders.	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).	week 20
Clinical Global Impression-Improvement (CGI-I).	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.	week 20
Clinical Global Impression-severity (CGI-S) scale	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".	week 20
Clinical Global Impression-Improvement (CGI-I) in relation to inflammatory markers	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.	week 20
Adverse event: Any Adverse Reactions (AAR). Safety and tolerability of Rituximab	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.	week 20

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Personal and Social Performance Scale (PSP)	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.	week 40
Clinical Global Impression-Improvement (CGI-I). Proportion of responders.	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).	week 40
Yale-Brown obsessive- compulsive scale (Y-BOCS)	Y-BOCS maps symptoms and measures severity of obsessive-compulsive symptoms by a clinician. Y-BOCS has a range between 0 and 40 points, higher scores denotes worse symptoms. Outcome is measured as change in Y-BOCS score from baseline. At least 35% reduction in the score since baseline is defined as a response.	week 40
Clinical Global Impression-severity (CGI-S) scale	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".	week 40
Clinical Global Impression-Improvement (CGI-I) in relation to inflammatory markers	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.	week 40
Changes in cognitive functioning	Improvement in cognitive tests using a subset of tests included in Wechsler Adult Intelligence Scale (WAIS) (i.e. Block design, digit span, letter number sequencing and digit symbol coding, visuospatial test).	week 20
CGI-I in relation to treatment and evaluated by the treating clinician, the patient's self-assessment and a next of kin	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.	week 40
B cell subpopulations in relation to clinical response	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.	week 20
Life quality measured with Brunnsviken Brief Quality of Life Scale (BBQ)	BBQ is a 12-item self-rated measurement of life satisfaction, it is a likert scale, range 0-48. Higher scores denote higher life satisfaction.	week 40

Collaborators and Investigators

• Sponsor: Region Örebro County
• Collaborators: Örebro University, Sweden
• Investigators: Principal Investigator: Susanne Bejerot, MD, Region Örebro Län

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 8, 2019
• Primary Completion (ACTUAL): March 31, 2022
• Study Completion (ACTUAL): March 31, 2022

Study Registration Dates

• First Submitted: May 30, 2019
• First Submitted That Met QC Criteria: June 11, 2019
• First Posted (ACTUAL): June 12, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 10, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Immunopsychiatry; pediatric acute-onset neuropsychiatric syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Personality Disorders; Anxiety Disorders; Disease; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: EudraCT Number: 2018-004619-28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Details that can identify the patients will not be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No