SchizophreniaTOPSYNCT02882204
Tracking Outcomes in Psychosis
An observational study of Schizophrenia, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- How many people
- 168 participants
- Where
- 1 siteCanada
- Study dates
- 1 Mar 2016to 1 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Study population includes two groups of individuals: 1. First Episode psychotic patients: This group will contain 84 new patients enrolled in the Prevention and early Intervention Program for Psychosis. 2. Chronic Patients: This group will contain 42 patients who have been enrolled in the Prevention and Early Intervention Program for Psychosis for >3 years. 3. Healthy Controls: This group will contain 42 healthy controls not being treated for a major mental illness defined using DSM-V criteria.
Who may be able to join
- 16-45 years old
- Outpatient of the Prevention and Early Intervention Program for Psychosis
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Robarts Research
London, Ontario, N6A 5B7
Lena Palaniyappan, MBBS, PhD, 519-685-8054, lena.palaniyappan@lhsc.on.ca
About this study
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.
Read the 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.
- Conditions
- Schizophrenia
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| First Episode Patients | First episode patients new to the PEPP program. | |
| Chronic Patients | Existing patients who have been enrolled in the PEPP program for >3 years | |
| Healthy Controls | Healthy controls who are not currently in treatment for any major mental illness defined using DSM-V criteria. | |
| Cliniucal High Risk patients | Patients who are accessing PEPP services during the prodromal phase of psychotic illness. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 Months
Time to remission of positive symptoms of psychosis
The time between baseline and remission of positive symptoms based on PANSS-8
Measured: 30 months
Time to remission of negative symptoms of psychosis
The amount of time between baseline and remission of negative symptoms based on PANSS-8
Measured: 30 months
Emergence of treatment resistance using operational criteria
Measured: 30 months
Secondary outcomes (3)
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.
Measured: 1-2.5 years
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
Measured: 30 months
Changes in myelin content
Longitudinal changes in myelin content as measured using quantitative t1 images
Measured: 30 months (follow up period for first episode patients)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2016 (estimated)
- Study start1 Mar 2016
- Primary completionDec 2022 (estimated)
- Study completion1 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 168 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Collaborators
- University of Western Ontario, Canada
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02882204
- Sponsor's protocol ID
- 10014067
- Acronym
- TOPSY
- Status last verified
- Sep 2019
- First submitted
- 24 Aug 2016
- Last updated
- 21 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Harrow M, Marengo JT. Schizophrenic thought disorder at followup: its persistence and prognostic significance. Schizophr Bull. 1986;12(3):373-93. doi: 10.1093/schbul/12.3.373.
PubMed 3764358Palaniyappan 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.
PubMed 26232240Liddle 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. doi: 10.1192/bjp.181.4.326.
PubMed 12356660Aoyama N, Theberge 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.
PubMed 21628707American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders (DSM-5®) (2013).
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tracking Outcomes in Psychosis
- ClinicalTrials.gov ID
- NCT02882204
- Acronym / sponsor ID
- TOPSY / 10014067
- Conditions
- Schizophrenia
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 168 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Collaborators
- University of Western Ontario, Canada
- Study start
- 1 Mar 2016 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- 1 Dec 2023 (estimated)
- First posted
- 29 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| First Episode Patients | – | –First episode patients new to the PEPP program. |
| Chronic Patients | – | –Existing patients who have been enrolled in the PEPP program for >3 years |
| Healthy Controls | – | –Healthy controls who are not currently in treatment for any major mental illness defined using DSM-V criteria. |
| Cliniucal High Risk patients | – | –Patients who are accessing PEPP services during the prodromal phase of psychotic illness. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Study population includes two groups of individuals: 1. First Episode psychotic patients: This group will contain 84 new patients enrolled in the Prevention and early Intervention Program for Psychosis. 2. Chronic Patients: This group will contain 42 patients who have been enrolled in the Prevention and Early Intervention Program for Psychosis for >3 years. 3. Healthy Controls: This group will contain 42 healthy controls not being treated for a major mental illness defined using DSM-V criteria.
Key inclusion criteria (2 listed)
- 16-45 years old
- Outpatient of the Prevention and Early Intervention Program for Psychosis
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in Thought Language Index Score between baseline and 6 months
Time frame: 6 Months
Predicting the change in TLI score based on baseline anatomical abnormalities identified through MRI
Time to remission of positive symptoms of psychosis
Time frame: 30 months
The time between baseline and remission of positive symptoms based on PANSS-8
Time to remission of negative symptoms of psychosis
Time frame: 30 months
The amount of time between baseline and remission of negative symptoms based on PANSS-8
Emergence of treatment resistance using operational criteria
Time frame: 30 months
3 secondary outcomes
Change in Thought Language Index score between baseline and longitudinal follow up-dates (12 months, 18 months, 24 months and 30 months)
Time frame: 1-2.5 years
Change in overall symptoms over time
Time frame: 30 months
Changes in myelin content
Time frame: 30 months (follow up period for first episode patients)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2020.
- Background: PubMed 3764358Harrow M, Marengo JT. Schizophrenic thought disorder at followup: its persistence and prognostic significance. Schizophr Bull. 1986;12(3):373-93. doi: 10.1093/schbul/12.3.373.
- Background: PubMed 26232240Palaniyappan 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.
- Background: PubMed 12356660Liddle 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. doi: 10.1192/bjp.181.4.326.
- Background: PubMed 21628707Aoyama N, Theberge 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.
- BackgroundAmerican Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders (DSM-5®) (2013).
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Schizophrenia, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lena Palaniyappan, MD, PhD (519.685.8054, lena.palaniyappan.@lhsc.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Thought Language Index Score between baseline and 6 months (time frame: 6 Months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02882204, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2020.