Tracking Outcomes in Psychosis

Schizophrenia Clinical Trial

— TOPSY  

Official title:

Tracking Outcomes in Psychosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02882204
• Other study ID #: 10014067
• Status: Recruiting
• Start date: March 1, 2016
• Est. completion date: December 1, 2023

Study information

• Verified date: September 2019
• Source: Lawson Health Research Institute
• Contact: Lena Palaniyappan, MD, PhD
• Phone: 519.685.8054
• Email: lena.palaniyappan.[@]lhsc.on.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 168
• Est. completion date: December 1, 2023
• Est. primary completion date: December 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• 16-45 years old

• Outpatient of the Prevention and Early Intervention Program for Psychosis

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

Related Conditions & MeSH terms

• Schizophrenia

Locations

Country	Name	City	State
Canada	Robarts Research	London	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Lawson Health Research Institute	University of Western Ontario, Canada

Country where clinical trial is conducted

Canada, 

References & Publications (5)

American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders (DSM-5®) (2013).

Aoyama N, Théberge J, Drost DJ, Manchanda R, Northcott S, Neufeld RW, Menon RS, Rajakumar N, Pavlosky WF, Densmore M, Schaefer B, Williamson PC. Grey matter and social functioning correlates of glutamatergic metabolite loss in schizophrenia. Br J Psychiatry. 2011 Jun;198(6):448-56. doi: 10.1192/bjp.bp.110.079608. — View Citation

Harrow M, Marengo JT. Schizophrenic thought disorder at followup: its persistence and prognostic significance. Schizophr Bull. 1986;12(3):373-93. — View Citation

Liddle PF, Ngan ET, Caissie SL, Anderson CM, Bates AT, Quested DJ, White R, Weg R. Thought and Language Index: an instrument for assessing thought and language in schizophrenia. Br J Psychiatry. 2002 Oct;181:326-30. — View Citation

Palaniyappan L, Mahmood J, Balain V, Mougin O, Gowland PA, Liddle PF. Structural correlates of formal thought disorder in schizophrenia: An ultra-high field multivariate morphometry study. Schizophr Res. 2015 Oct;168(1-2):305-12. doi: 10.1016/j.schres.2015.07.022. Epub 2015 Jul 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Thought Language Index Score between baseline and 6 months	Predicting the change in TLI score based on baseline anatomical abnormalities identified through MRI	6 Months
Primary	Time to remission of positive symptoms of psychosis	The time between baseline and remission of positive symptoms based on PANSS-8	30 months
Primary	Time to remission of negative symptoms of psychosis	The amount of time between baseline and remission of negative symptoms based on PANSS-8	30 months
Primary	Emergence of treatment resistance using operational criteria		30 months
Secondary	Change in Thought Language Index score between baseline and longitudinal follow up-dates (12 months, 18 months, 24 months and 30 months)	Net change in TLI score as predicted by anatomical abnormalities associated with imaging at various imaging time points.	1-2.5 years
Secondary	Change in overall symptoms over time	Tracking changes in scores on the PANSS-8 over the 30 months of follow up for first episode patients	30 months
Secondary	Changes in myelin content	Longitudinal changes in myelin content as measured using quantitative t1 images	30 months (follow up period for first episode patients)