Rituximab Treatment for Psychosis and/or Obsessive Compulsive Disorder With Probable Immune System Involvement

• Status: Not yet recruiting
• Trial end date: 2025-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective for this study is to evaluate whether Rituximab as compared to placebo is a clinically effective treatment for a subgroup of patients suffering from psychosis and/or obsessive-compulsive disorder (OCD) or -behavior (OCB) where there is an indication of immune system involvement.

The secondary objectives of this study are

1. To assess whether Rituximab treatment (with the doses and timing described below) as compared to placebo is associated with amelioration in psychiatric symptomatology

2. To assess whether Rituximab treatment as compared to placebo is associated with improvement in executive functions

3. To assess whether Rituximab treatment as compared to placebo is associated with amelioration in neurological symptoms

4. To evaluate the longevity of psychiatric, neurological and executive improvements associated with Rituximab treatment for up to 16 months after the first infusion (i.e. 12 months after the last infusion)

5. To evaluate whether Rituximab treatment as described is safe for these patients.

The exploratory objectives of this study are

1. To assess changes in blood and cerebrospinal fluid (CSF) markers for immune activity associated with Rituximab treatment compared to placebo

2. To assess statistical associations between biological markers in blood or CSF and clinical response

3. To describe changes in somatic symptoms associated with treatment with Rituximab vs placebo for patients with initial symptoms in the questionnaires

4. To describe changes on MR and EEG associated with treatment with Rituximab vs placebo for patients with initial pathology in these examination

5. To study immune mechanisms coupled with psychiatric symptoms, possibly identifying novel biomarkers with potential for subtyping encephalopathies with immune engagement, using biobank cells, blood and CSF samples collected from the participants.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Uppsala University Hospital
• Collaborator: Uppsala University
• Treatments: Rituximab

Criteria

INCLUSION CRITERIA

General criteria

1. Diagnostic criteria: ICD 10 at least one of the following ICD 10 diagnoses:

1. Obsessive-compulsive disorder ICD F42 or

2. Obsessive-compulsive behavior ICD R46.81 AND/OR

3. Schizophrenia, delusional, and other non-mood psychotic disorders, namely

F20 Schizophrenia

F22 Delusional disorders

F23 Brief psychotic disorder

F25 Schizoaffective disorders

F28 Other psychotic disorder not due to a substance or known physiological condition

F29 Unspecified psychosis not due to a substance or known physiological condition

2. Age: 18-55

3. Severity: Clinical Global impression (CGI): Minimum score of "4 = Moderately ill"

4. Swedish or English proficiency

5. The patient has tried at least 2 standard psychiatric medications at maximal tolerable or maximal recommended dosage for his/her current condition over a period of 6 months, but has not improved significantly

6. Medication has been unchanged for at least one month prior to study start

7. Signed informed consent

8. Use of adequate contraception

9. Radiological evidence of brain atrophy and scarring are absent

10. The clinical picture indicates active inflammatory activity (see specific criteria below), potential for rehabilitation and time from disease and/or episode debut is no longer than 10 years.

Specific criteria

11. Acute (<12 weeks) or atypical debut, or episodes of any of the following:

1. Symptoms of encephalopathy:

psychotic symptoms, including hallucinations, delusions, paranoia, disorganized speech, disorganized behavior

agitation, confusion

sudden change in personality as perceived by the social environment

drowsiness

loss of functions in daily Life

cognitive problems (memory, speech, learning)

emotional dysregulation

2. Focal neurological symptoms, e.g. ataxia, dystonia, myoclonus, sensory losses, paresthesia

3. Psychomotor anomaly, e.g.retardation, catatonic symptoms, parkinsonism

4. Loss of drive (sleep, appetite, libido, motivation)

5. Obsessions, compulsions (OCD/OCB),

6. Hypo- or hypervigilance (for e.g sounds, emotions, other peoples´ or own behavior)

7. Sleeping disorders,

AND

12. At least one of the following criteria:

1. Prodromal phase with infection or symptoms of infection (fever, malaise, etc)

2. Clinical improvement of psychiatric symptoms after treatment with anti-inflammatory medications other than antibody therapy (such as steroids, NSAIDs IVIG, plasmaphereses), or antibiotics

3. Radiological evidence of neuroinflammation (MR)

4. EEG pathology or witnessed epileptic seizure

5. Biochemical evidence of inflammation, autoimmunity or blood-brain barrier dysfunction in blood or CSF samples, such as one of the following:

presence of oligoclonal bands

elevated CSF cell count

elevated albumin quotient, or elevated albumin in CSF

elevated Immunoglobulin G (IgG) ratio

elevated levels of neurofilament

6. Patient history of autoimmune disorder not associated with neuroinflammation, such as type 1 diabetes, rheumatoid arthritis, Sjögren´s syndrome, inflammatory bowel disease (IBD, comprising Crohn´s disease and ulcerative colitis), celiac disease, Grave´s disease, Hashimoto's thyroiditis

7. Biochemical indication of autoimmunity such as elevated serum anti-thyroid peroxidase (TPO) antibody, antinuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), rheumatoid factor (RF) or glutamic acid decarboxylase (GAD) antibodies, PANDAS panel with relationship to symptom development.

EXCLUSION CRITERIA

13. Concomitant malignancies or previous malignancies within the last five years

14. Cannot comply with vaccination recommendations

15. History of severe allergic or anaphylactic reactions in conjunction with prior treatment with monoclonal antibodies

16. Prior antibody therapy including Rituximab (MabThera®/Rituxan®)

17. Patient has been treated with clozapine (which may have immunosuppressant effect), systemic corticosteroids or IVIG within 60 days prior to screening visit

18. Prior treatment with immunosuppressant medications (not including systemic corticosteroids and IVIG) for other medical condition

19. History of or positive screening for HIV, Tuberculosis, Hepatitis B and/or Hepatitis C (ever)

20. Heart disease such as previous heart attack, arrhythmia or heart failure, coronary insufficiency

21. Current drug, alcohol, or chemical abuse

22. Pregnancy at any time during the study

23. Known chronical significant bacterial/viral/fungal infections at infusion date

24. Diagnosis of well-established neuroinflammatory disease such as Multiple Sclerosis (MS) (ICD codes G00-G09, G35-G37) or systemic lupus erythematosus (SLE) (M32)

25. Tested positive for autoantibodies in serum or CSF associated to known and treatable neuroinflammatory disease (such as neuroborreliosis, treatable autoimmune encephalitis). Patients having completed recommended treatment without significant improvement may still be included in this study.

26. History of any illness that in the opinion of the investigator may jeopardize the ability of the patient to participate in the study.

27. Patient is enrolled in another medical trial.