Psychosis-Associated Neuroinflammation in Schizophrenia (PANS)

Phase 0 Clinical Protocol: A Longitudinal and Multimodal Exploratory Study to Evaluate a Neuroinflammatory Hypothesis in Patients With Schizophrenia Compared to Young Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Psychosis
• Intervention / Treatment: Radiation: [18F]-PBR111 Positron Emission Tomography (PET); Behavioral: Cognitive and psychomotor tasks; Biological: Blood sampling

• Study Type: Observational
• Enrollment (Actual): 106

Contacts and Locations

Study Locations

• Belgium
  • Antwerp
    • Mortsel, Antwerp, Belgium, 2640
      • Psychiatrisch Ziekenhuis Sint-Amedeus
  • Antwerpen
    • Boechout, Antwerpen, Belgium, 2530
      • Psychiatrisch Ziekenhuis Broeders Alexianen
    • Duffel, Antwerpen, Belgium, 2570
      • Psychiatrisch Ziekenhuis St Norbertus

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Young schizophrenia patients admitted to psychiatric hospital for acute relapse or first-episode of psychosis

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy controls; Healthy age- and sex-matched controls	Radiation: [18F]-PBR111 Positron Emission Tomography (PET); [18F]-PBR111 radioligand to assess binding to TSPO; Behavioral: Cognitive and psychomotor tasks; Cognitive and psychomotor tasks on digitizing tablet; Biological: Blood sampling; Blood sampling for peripheral inflammatory and neurotoxicity markers
Schizophrenia patients; Young schizophrenia patients 18-40y	Radiation: [18F]-PBR111 Positron Emission Tomography (PET); [18F]-PBR111 radioligand to assess binding to TSPO; Behavioral: Cognitive and psychomotor tasks; Cognitive and psychomotor tasks on digitizing tablet; Biological: Blood sampling; Blood sampling for peripheral inflammatory and neurotoxicity markers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regional VT of [18F]PBR111	Regional distribution volume in tissue (VT) of 2-(6-chloro-2-(4-(3-fluoropropoxy)phenyl)imidazo(1,2-a)pyridin-3-yl)-N,N-diethylacetamide (PBR111) labelled with fluorine-18 (18F) in schizophrenia patients and age- , gender-, and translocator protein (TSPO) binding profile- matched healthy controls	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral markers	Levels and ratios of inflammatory and neurotoxicity markers in blood samples of schizophrenia patients compared to healthy age- and gender-matched healthy controls.	2 years

Collaborators and Investigators

• Sponsor: Universiteit Antwerpen
• Collaborators: Janssen Research & Development, LLC; Agentschap voor Innovatie door Wetenschap en Technologie
• Investigators: Principal Investigator: Bernard Sabbe, MD PhD, Universiteit Antwerpen

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: December 9, 2013
• First Submitted That Met QC Criteria: December 9, 2013
• First Posted (Estimate): December 12, 2013

Study Record Updates

• Last Update Posted (Actual): August 31, 2017
• Last Update Submitted That Met QC Criteria: August 30, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Schizophrenia; Psychosis; Neuroinflammation; Microglial activation
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mental Disorders
• Other Study ID Numbers: CAPRI13/37/348; B300201318710 (Other Identifier: Belgian Study Registration Number)