Lurasidone Vs Olanzapine on Neurotrophic Biomarkers and Cardiometabolic Parameters in Unmedicated Schizophrenia

Study Overview
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Brief Summary
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Schizophrenia (SCZ) is a chronic, severe and disabling mental disorder with unclear etiology and pathophysiology concerned with neuro-developmental,neurodegenerative abnormalities and cognitive impairmentslinked to behavioural changes.According to neurotrophic hypothesis, the changes result due to the abnormal regulation of neurotrophic factor, especially the decreased serum brain derived neurotrophic factor (BDNF) validated by several meta-analyses. However, the regulation of nerve growth factor (NGF) in SCZ remains unclear because of the inconsistent findings from the previous clinical studies. Lurasidone is a novel antipsychotic drug approved for adult SCZ and for affective symptomatology & cognitive deficits. Principal advantages over some other second-generation antipsychotics are its highly favourable metabolic profile and once daily dosing regimen. Some of the studies indicate that risperidone, olanzapine, clozapine & aripiprazole might not alter BDNF levels, at least within 8 weeks of treatment.While other two studies with olanzapine suggest that BDNF might influence the response to monotherapy in SCZ patients.All these previous studies are non-conclusive & contradictory to each other which draw our attention for doing the research further to reach a conclusive result about the effect of olanzapine and lurasidone on neurotrophic biomarkers in SCZ.

Detailed Description
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Schizophrenia (SCZ) is a chronic, severe and disabling mental disorder with unclear aetiology and pathophysiology concerned with neuro-developmental,neurodegenerative abnormalities and cognitive impairments linked to behavioural changes.According to neurotrophic hypothesis, the changes result due to the abnormal regulation of neurotrophic factor, especially the decreased serum brain derived neurotrophic factor (BDNF) validated by several meta-analyses. However, the regulation of nerve growth factor (NGF) in SCZ remains unclear because of the inconsistent findings from the previous clinical studies. Lurasidone is a novel antipsychotic drug approved for adult SCZ and for affective symptomatology & cognitive deficits. Principal advantages over some other second-generation antipsychotics are its highly favourable metabolic profile and once daily dosing regimen. Some of the studies indicate that risperidone, olanzapine, clozapine & aripiprazole might not alter BDNF levels, at least within 8 weeks of treatment.While other two studies with olanzapine suggest that BDNF might influence the response to monotherapy in SCZ patients.All these previous studies are non-conclusive & contradictory to each other which draw our attention for doing the research further to reach a conclusive result about the effect of olanzapine and lurasidone on neurotrophic biomarkers in SCZ. Most of the antipsychotic drugs prescribed for SCZ are based on the dopamine hypothesis. In recent times, neurotrophic hypothesis gained importance in the pathophysiology of SCZ. So, our study may enable psychiatrist to choose a better antipsychotic drug having effect on both dopamine as well as neurotrophic factors. Previously there were no studies on effect of lurasidone on neurotrophic factors in SCZ & also there was no head-on comparison of lurasidone and olanzapine

Official Title
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Effect of Lurasidone Vs Olanzapine on Neurotrophic Biomarkers and Cardiometabolic Parameters in First Episode Untreated Schizophrenia: A Randomized, Open Label, Active Controlled Study

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Olanzapine
* Drug: Lurasidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All treatment naive patients clinically diagnosed first episode of SCZ according to ICD-10 Patients of either sex with age range 18-45 years Treatment naïve patients Exclusion Criteria: Other Psychotic spectrum disorders (F21- F29) Highly agitated/ violent/ suicidal patients who need immediate treatment Patients with comorbid substance abuse except Nicotine use or history of organicity Patients with known history of diabetes mellitus, hypertension or any long standing significant medical illness/ significant neurological impairment/ clinical observable mental retardation Pregnant and nursing women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized, open label, active controlled study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Olanzapine<br>Olanzapine will be prescribed at a dose of 10mg once daily orally for 6 weeks | Drug: Olanzapine<br>* Olanzapine 10mg once daily orally for 6 weeks<br>|
| Experimental: Lurasidone<br>Lurasidone will be prescribed at a dose of 80mg/day once daily orally for 6 weeks | Drug: Lurasidone<br>* Lurasidone 80mg once daily orally for 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum brain derived neurotrophic factor (BDNF) | the change in serum level of BDNF from baseline after treatment with lurasidone or olanzapine | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum nerve growth factor (NGF) | the change in serum level of NGF from baseline after treatment with lurasidone or olanzapine | 6 weeks | 
| Serum Neurotrophin 3 (NT3) | the change in serum level of NT3 from baseline after treatment with lurasidone or olanzapine | 6 weeks | 
| PANSS score | To determine the association (if any) between change in serum neurotrophic factor and PANSS score | 6 weeks | 
| Social and occupational functioning assessment scale (SOFAS) | To determine the association (if any) between change in serum neurotrophic factor and SOFAS (Social and occupational functioning assessment scale) score | 6 weeks | 
| Serum hsCRP | to assess cardiovascular risk in schizophrenia | 6 weeks | 
| Serum Insulin | to assess insulin resistance | 6 weeks | 
| LDL/HDL ratio | to assess dyslipidemia and cardiovascular risk | 6 weeks | 
| Fasting blood sugar | to assess dysglycemia | 6 weeks | 
| Glycosylated Hemoglobin (HbA1c) | to assess dysglycemia | 6 weeks | 
| High Density Lipoprotein (HDL) | to assess dyslipidemia | 6 week | 
| Low Density Lipoprotein (LDL) | to assess dyslipidemia | 6 week | 
| Very Low Density Lipoprotein (VLDL) | to assess dyslipidemia | 6 week | 
| Serum Triglyceride | to assess dyslipidemia | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lurasidone, Olanzapine, Brain derived neurotrophic factor, Nerve growth factor, Neurotrophin 3