Tracking Outcomes in Psychosis

• Conditions: Schizophrenia

• Registration Number: NCT02882204
• Lead Sponsor: Lawson Health Research Institute

Brief Summary

The investigators propose to study the brain processes that result in thought and language disorder and influence outcomes seen in patients with schizophrenia using a combination of brain scans and clinical assessments. The project will assess patients at various stages of psychosis (Clinical high risk, first episode and chronic stage \>3 years of illness) referred to the Prevention and Early Intervention in Psychosis Programme using Magnetic Resonance Imaging (MRI scans). To track the outcome of this illness, investigators will follow-up patients over 3 years and collect MRI scans over four sessions for each first episode patient, and two sessions for clinical high risk patients, chronic patients, and healthy controls. Participants will also complete a clinical assessment examining symptoms and functioning as per the current clinical practice within the PEPP program at each scanning session.

Detailed Description

OBJECTIVES: The objective of this study is to investigate the pathophysiology of Formal Thought Disorder and variable outcomes in the early stages of schizophrenia. In particular, investigators aim to test the hypothesis that 1. Anatomical abnormalities involving the grey matter of the Anterior Insula and Medial Prefrontal Cortex in first episode schizophrenia predicts FTD that persists by 6 months of illness 2. An excess of glutamine/glutamate, or reduction in glutathione, in Medial Prefrontal Cortex at index episode will be associated with persistent FTD 3.Aberrant connectivity between Anterior Insula and Medial Prefrontal Cortex will specifically predict the severity of persistent FTD irrespective of the stage of illness; the change in this connectivity will track the variable 3-year outcome among patients with first episode of psychosis.

METHODS: This study will employ a cross-sectional design recruiting n=126 participants from the Prevention \& Early Intervention Program for Psychoses (PEPP). Four groups of participants will be assessed: patients at a later stage of schizophrenia (chronic illness group) (n=42), newly referred first episode group of PEPP patients (n=84), Clinical High Risk patients (n=60) and healthy Controls (n=45). Measurements: Patients will be diagnosed using the criteria for schizophrenia according to DSM-V(34). Demographic variables such as age, gender and parental socioeconomic status will be recorded to adjust for potential confounding effects. Patients will undergo baseline assessments to assess seven features of FTD (poverty of speech, weakening of goal, perseveration, looseness, peculiar word usage, peculiar sentence usage and peculiar logic) in line with the validated procedure for administering Thought Language Index \[TLI\](17). First episode patients will undergo four 7T MRI scanning sessions over the course of 2.5 years (baseline, 6 months, 18 months, 30 months)lasting for 60 minutes each, as described in our previous work (15). During this time, researchers will perform MR spectroscopy (MPFC voxel (31)), T1 weighted structural scan and eyes-closed, task-free, 6 minutes resting-state functional MRI. 6 months after the onset of first episode, the clinical assessment will be repeated using TLI. Patients with persistent FTD will be identified (from previous studies, 40% of patients are expected to have persistent FTD (9)) and separated from patients who have no FTD at 6-months time point. Patients with established illness will undergo only 2 scans: baseline and 1 year later.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2016-03-01
• Study First Submitted: 2016-08-24
• Study First Submitted QC: 2016-08-24
• Study First Posted: 2016-08-29
• Status Verified: 2019-09
• Last Update Submitted: 2020-02-20
• Last Update Posted: 2020-02-21
• Primary Completion: 2022-12
• Study Completion: 2023-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 168

Inclusion Criteria

• 16-45 years old
• Outpatient of the Prevention and Early Intervention Program for Psychosis

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Exclusion Criteria

• Drug or alcohol dependence in past year
• History of head injury (with associated unconsciousness for any period)
• Mental retardation or suffering from medical conditions such as untreated hypertension, diabetes, hepatic/renal insufficiency, neurological illnesses
• Otherwise unable to provide informed consent

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in Thought Language Index Score between baseline and 6 months	6 Months	Predicting the change in TLI score based on baseline anatomical abnormalities identified through MRI
Emergence of treatment resistance using operational criteria	30 months
Time to remission of positive symptoms of psychosis	30 months	The time between baseline and remission of positive symptoms based on PANSS-8
Time to remission of negative symptoms of psychosis	30 months	The amount of time between baseline and remission of negative symptoms based on PANSS-8

Secondary Outcome Measures

Name	Time	Method
Change in Thought Language Index score between baseline and longitudinal follow up-dates (12 months, 18 months, 24 months and 30 months)	1-2.5 years	Net change in TLI score as predicted by anatomical abnormalities associated with imaging at various imaging time points.
Change in overall symptoms over time	30 months	Tracking changes in scores on the PANSS-8 over the 30 months of follow up for first episode patients
Changes in myelin content	30 months (follow up period for first episode patients)	Longitudinal changes in myelin content as measured using quantitative t1 images

Trial Locations

Locations (1)

Robarts Research; 🇨🇦 London, Ontario, Canada