Psychosis-Associated Neuroinflammation in Schizophrenia

NCT ID: NCT02009826

Last Updated: 2017-08-31

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 106 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2017-02-28

Brief Summary

Previous research has suggested central nervous system inflammatory activity to be critically involved in disease development and progression in schizophrenia, with a complex interplay of inflammatory mechanisms leading to the development of brain abnormalities and medical symptoms related to schizophrenia. However, the mutual interactions of different inflammatory pathways and their relation to disease course have not been sufficiently studied. This study therefore aims to explore the interaction of neuroinflammatory mechanisms in patients with schizophrenia and to assess whether the inflammatory activity in schizophrenia is state-dependent and occurs mainly during psychotic episodes.

Conditions

Schizophrenia; Psychosis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Healthy controls

Healthy age- and sex-matched controls

[18F]-PBR111 Positron Emission Tomography (PET)

Intervention Type: RADIATION

\[18F\]-PBR111 radioligand to assess binding to TSPO

Cognitive and psychomotor tasks

Intervention Type: BEHAVIORAL

Cognitive and psychomotor tasks on digitizing tablet

Blood sampling

Intervention Type: BIOLOGICAL

Blood sampling for peripheral inflammatory and neurotoxicity markers

Schizophrenia patients

Young schizophrenia patients 18-40y

[18F]-PBR111 Positron Emission Tomography (PET)

Intervention Type: RADIATION

\[18F\]-PBR111 radioligand to assess binding to TSPO

Cognitive and psychomotor tasks

Intervention Type: BEHAVIORAL

Cognitive and psychomotor tasks on digitizing tablet

Blood sampling

Intervention Type: BIOLOGICAL

Blood sampling for peripheral inflammatory and neurotoxicity markers

Interventions

[18F]-PBR111 Positron Emission Tomography (PET)

\[18F\]-PBR111 radioligand to assess binding to TSPO

Intervention Type: RADIATION

Cognitive and psychomotor tasks

Cognitive and psychomotor tasks on digitizing tablet

Intervention Type: BEHAVIORAL

Blood sampling

Blood sampling for peripheral inflammatory and neurotoxicity markers

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Be a man or woman between 18 and 40 years of age, inclusive.
• Have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in this study.
• Be medically stable on the basis of physical examination and vital signs performed at Screening.
• Be medically stable on the basis of clinical laboratory tests performed at Screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study.
• Be willing and able to adhere to the prohibitions and restrictions specified in the protocol.

Schizophrenia subjects:

• Fulfill DSM-V criteria for the schizophrenia spectrum (DSM-V #295.1-295.6, 295.9, 298.9)
• Be admitted to hospital for first-episode psychosis or acute relapse of psychosis, as defined by:

total score of ≥14 on the positive scale of the "Positive and Negative Syndrome Scale" (PANSS) and at least a score of 5 on 1 item or a score of 4 on 2 "psychotic" PANSS items P2, P3, P5 or G9 at Screening.

Exclusion Criteria

• Use of nonsteroidal antiinflammatory drugs, paracetamol, immunosuppressant or immunostimulating drugs within 21 days of screening.
• Use of systemic corticosteroids within 21 days of screening.
• Has a history of drug or alcohol dependence according to DSM-V criteria, except nicotine or caffeine, within 6 months before screening.
• Has history of (co-morbid) somatization or mood disorder according to DSM-V criteria within 6 months before screening.
• Has a positive test result for drugs of abuse or for alcohol at screening or test day.
• Female subjects only: is pregnant or breastfeeding
• Has a history of chronic or acute physical illness associated with abnormal immune changes within the 2 weeks before the study.
• Leukocytosis (i.e., white blood cell count ≤ 11 x109 /L) on screening and test days.
• Serology positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies, or HIV antibodies at screening.
• Has a medical history of any auto-immune disorder or chronic inflammatory disease.
• Has received electroconvulsive therapy in the last 6 months.
• Is currently enrolled in a study with an investigational study drug.
• Worsening or first time occurrence of significant suicidality
• Has donated blood within 3 months before screening.
• Has any condition that, in the opinion of the investigator, would compromise the wellbeing of the subject or the study or prevent the subject from meeting or performing study requirements.
• Low affinity binder of the TSPO, as determined by rs6971 polymorphism genotyping at Screening
• Use of benzodiazepines for 3x the half-life prior to PET-scan
• Presence of irremovable magnetic materials in or on the body
• Has a medical history of organic brain disease
• Has a medical history of traumatic brain injury
• Has a medical history of allergic reaction to any of the substances in the tracer fluid.
• Unwillingness or inability of subject to undergo PET and/or MRI scan (for example due to claustrophobia or lack of cooperation)

Healthy volunteers:

• Personal history of psychotic disorder
• Family history of psychotic or bipolar disorder in first-degree relatives
• Family history of auto-immune disorder in first-degree relatives

Schizophrenia patients:

• Calgary Depression Scale for Schizophrenia (CDSS) score >6 at screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Agentschap voor Innovatie door Wetenschap en Technologie

OTHER

Sponsor Role: collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: collaborator

Universiteit Antwerpen

OTHER

Sponsor Role: lead

Responsible Party

Dr Livia De Picker

Medical Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bernard Sabbe, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Universiteit Antwerpen

Locations

Psychiatrisch Ziekenhuis Broeders Alexianen

Boechout, Antwerpen, Belgium

Psychiatrisch Ziekenhuis St Norbertus

Duffel, Antwerpen, Belgium

Psychiatrisch Ziekenhuis Sint-Amedeus

Mortsel, Antwerp, Belgium

Countries

Belgium

Other Identifiers

B300201318710

Identifier Type: OTHER

Identifier Source: secondary_id

CAPRI13/37/348

Identifier Type: -

Identifier Source: org_study_id