Impact of Structural and Myelin Abnormalities on Cognitive Impairments in Recent-onset Schizophrenia - Before and After Lurasidone Treatment (MARYLU)

Study Overview
=================
Brief Summary
-----------------
The present longitudinal study aims to investigate the impact of lurasidone treatment in recent-onset psychosis patients. The effects of lurasidone will be studied primarily in terms of structural and myelin modifications, in relation to clinical outcomes, before and after treatment and in healthy controls. Furthermore, neuropsychological tests will be used to evaluate changes in cognitive performance.

Official Title
-----------------
Impact of Structural and Myelin Abnormalities on Cognitive Impairments in Recent-onset Schizophrenia - Before and After Lurasidone Treatment (MARYLU)

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Drug: Lurasidone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria for the experimental arm: Patients diagnosed with schizophrenia with onset in the past 5 years, diagnosed through a structured clinical interview (SCID-5 CV) Aged between 18 and 35 years Patients requiring treatment with lurasidone (independently from the inclusion in the present study) or that are being treated with lurasidone for 2 weeks maximum. no other psychotropic treatment during the 2 weeks preceding the beginning of the study Acceptance of the informed consent form for the participation to the study For women in childbearing age, negative pregnancy test (urine or blood Beta HCG) performed before the start of the treatment and use of a highly efficient contraceptive method (such as progestin contraceptives, estrogen-progestin contraceptives, IUD, IUS, bilateral fallopian tube blockage, vasectomized partner, sexual abstinence) throughout the duration of the treatment. Exclusion Criteria for the experimental arm: presence of other psychiatric and/or neurological diagnoses previous antipsychotic treatment, except for patients that have been treated with other antipsychotics for less than a month and that have not been treated in the two weeks preceding the beginning of the trial, who are considered eligible. contraindications to lurasidone treatment (as per summary of product characteristics) intellectual disability alcool or substance abuse in the previous 6 months presence of absolute or relative contraindications to MRI underage patients no negative pregnancy test or no use of a highly efficient contraceptive method pregnancy (if a patient becomes pregnant during the course of the study, the subject will be excluded from the study) Inclusion criteria for healthy controls: Aged between 18 and 35 years Acceptance of the informed consent form for the participation to the study Exclusion criteria for healthy controls: presence of psychiatric and/or neurological disorders family history of psychiatric disorders in 1st-degree relatives intellectual disability other medical conditions at the time of the study family history of hereditary neurological diseases alcool or substance abuse presence of absolute or relative contraindications to MRI underage patients no negative pregnancy test or no use of a highly efficient contraceptive method pregnancy (if a subject becomes pregnant during the course of the study, the subject will be excluded from the study)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Recent-onset schizophrenia<br>Patients diagnosed with schizophrenia with onset in the last 5 years that will be started on lurasidone or that have been on treatment with lurasidone for less than two weeks at the time of enrollment. | Drug: Lurasidone<br>* Treatment with lurasidone<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in brain structural modifications in terms of grey matter volume measured using magnetic resonance imaging | Modifications of grey matter volume measuring using magnetic resonance imaging | Before and at three months of treatment | 
| Changes in brain structural modifications in terms of cortical superficial area measured using magnetic resonance imaging | Modifications of cortical superficial area measuring using magnetic resonance imaging | Before and at three months of treatment | 
| Changes in brain structural modifications in terms of cerebral cortex thickness measuring using magnetic resonance imaging | Modifications of cerebral cortex thickness measuring using magnetic resonance imaging | Before and at three months of treatment | 
| Changes in myelin integrity measured using magnetic resonance imaging | Modifications of myelinization status measured in terms of myelin water fraction using magnetic resonance imaging | Before and at three months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of efficacy as assessed by Positive and Negative Syndrome Scale (PANSS) | Evaluation of changes in Positive and Negative Syndrome Scale with respect to the baseline. The PANSS is a 30-items scale assessing positive, negative, and general psychopathology associated with schizophrenia. Symptom severity for each item is rated in a 7-poing scale (1=absent; 7=extreme). | once per month during three months of treatment | 
| Evaluation of efficacy as assessed by Brief Psychiatric Rating Scale (BPRS) | Evaluation of changes in Brief Psychiatric Rating Scale (BPRS) with respect to the baseline. The BPRS is a scale assesses the level of 18 symptom constructs such as hostility, suspiciousness, hallucination, and grandiosity. Each symptom construct ranges from 1 (not present) to 7 (extremely severe). | once per month during three months of treatment | 
| Number of Adverse effects | Number of severe and non severe adverse effects | three months of treatment | 
| Changes in cognitive performance as assessed by Brief Assessment of Cognition in Schizophrenia (BAC-S) | Changes in Brief Assessment of Cognition in Schizophrenia (BAC-S) neuropsychological test scores with respect to the baseline. BAC-S is an assessment tool of cognitive function in patients with schizophrenia. | once per month during three months of treatment | 
| Structural differences in patients at baseline vs healthy controls measured using magnetic resonance imaging | Grey matter volume differences in patients at baseline vs healthy controls | baseline | 
| Myelinization differences in patients at baseline vs healthy controls measured using magnetic resonance imaging | Differences in terms of myelin water fraction in patients at baseline vs healthy controls | baseline |