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

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03304457
• Other study ID #: T/IM-F/17-18/29
• Status: Completed
• Phase: Phase 4
• Start date: August 25, 2017
• Est. completion date: March 25, 2018

Study information

• Verified date: March 2020
• Source: All India Institute of Medical Sciences, Bhubaneswar
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: March 25, 2018
• Est. primary completion date: March 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Olanzapine
Olanzapine 10mg once daily orally for 6 weeks
• Lurasidone
Lurasidone 80mg once daily orally for 6 weeks

Locations

Country	Name	City	State
India	AIIMS	Bhubaneshwar	Odisha

Sponsors (1)

Lead Sponsor	Collaborator
All India Institute of Medical Sciences, Bhubaneswar

Country where clinical trial is conducted

India, 

References & Publications (12)

Ahmed AO, Mantini AM, Fridberg DJ, Buckley PF. Brain-derived neurotrophic factor (BDNF) and neurocognitive deficits in people with schizophrenia: a meta-analysis. Psychiatry Res. 2015 Mar 30;226(1):1-13. doi: 10.1016/j.psychres.2014.12.069. Epub 2015 Jan — View Citation

Ashe PC, Berry MD, Boulton AA. Schizophrenia, a neurodegenerative disorder with neurodevelopmental antecedents. Prog Neuropsychopharmacol Biol Psychiatry. 2001 May;25(4):691-707. Review. — View Citation

Gejman PV, Sanders AR, Kendler KS. Genetics of schizophrenia: new findings and challenges. Annu Rev Genomics Hum Genet. 2011;12:121-44. doi: 10.1146/annurev-genom-082410-101459. Review. — View Citation

González-Pinto A, Mosquera F, Palomino A, Alberich S, Gutiérrez A, Haidar K, Vega P, Barbeito S, Ortiz A, Matute C. Increase in brain-derived neurotrophic factor in first episode psychotic patients after treatment with atypical antipsychotics. Int Clin Ps — View Citation

Hori H, Yoshimura R, Yamada Y, Ikenouchi A, Mitoma M, Ida Y, Nakamura J. Effects of olanzapine on plasma levels of catecholamine metabolites, cytokines, and brain-derived neurotrophic factor in schizophrenic patients. Int Clin Psychopharmacol. 2007 Jan;22 — View Citation

Matza LS, Buchanan R, Purdon S, Brewster-Jordan J, Zhao Y, Revicki DA. Measuring changes in functional status among patients with schizophrenia: the link with cognitive impairment. Schizophr Bull. 2006 Oct;32(4):666-78. Epub 2006 Jul 7. Review. — View Citation

Nikolac Perkovic M, Nedic Erjavec G, Zivkovic M, Sagud M, Uzun S, Mihaljevic-Peles A, Kozumplik O, Muck-Seler D, Pivac N. Association between the brain-derived neurotrophic factor Val66Met polymorphism and therapeutic response to olanzapine in schizophren — View Citation

Owen MJ, O'Donovan MC, Thapar A, Craddock N. Neurodevelopmental hypothesis of schizophrenia. Br J Psychiatry. 2011 Mar;198(3):173-5. doi: 10.1192/bjp.bp.110.084384. — View Citation

Pérez-Neri I, Ramírez-Bermúdez J, Montes S, Ríos C. Possible mechanisms of neurodegeneration in schizophrenia. Neurochem Res. 2006 Oct;31(10):1279-94. Epub 2006 Sep 28. Review. — View Citation

van Os J, Rutten BP, Poulton R. Gene-environment interactions in schizophrenia: review of epidemiological findings and future directions. Schizophr Bull. 2008 Nov;34(6):1066-82. doi: 10.1093/schbul/sbn117. Epub 2008 Sep 12. Review. — View Citation

Yoshimura R, Hori H, Sugita A, Ueda N, Kakihara S, Umene W, Nakano Y, Shinkai K, Mitoma M, Ohta M, Shinkai T, Nakamura J. Treatment with risperidone for 4 weeks increased plasma 3-methoxy-4-hydroxypnenylglycol (MHPG) levels, but did not alter plasma brain — View Citation

Yoshimura R, Ueda N, Hori H, Ikenouchi-Sugita A, Umene-Nakano W, Nakamura J. Different patterns of longitudinal changes in plasma levels of catecholamine metabolites and brain-derived neurotrophic factor after administration of atypical antipsychotics in — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum brain derived neurotrophic factor (BDNF)	the change in serum level of BDNF from baseline after treatment with lurasidone or olanzapine	6 weeks
Secondary	serum nerve growth factor (NGF)	the change in serum level of NGF from baseline after treatment with lurasidone or olanzapine	6 weeks
Secondary	Serum Neurotrophin 3 (NT3)	the change in serum level of NT3 from baseline after treatment with lurasidone or olanzapine	6 weeks
Secondary	PANSS score	To determine the association (if any) between change in serum neurotrophic factor and PANSS score	6 weeks
Secondary	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
Secondary	Serum hsCRP	to assess cardiovascular risk in schizophrenia	6 weeks
Secondary	Serum Insulin	to assess insulin resistance	6 weeks
Secondary	LDL/HDL ratio	to assess dyslipidemia and cardiovascular risk	6 weeks
Secondary	Fasting blood sugar	to assess dysglycemia	6 weeks
Secondary	Glycosylated Hemoglobin (HbA1c)	to assess dysglycemia	6 weeks
Secondary	High Density Lipoprotein (HDL)	to assess dyslipidemia	6 week
Secondary	Low Density Lipoprotein (LDL)	to assess dyslipidemia	6 week
Secondary	Very Low Density Lipoprotein (VLDL)	to assess dyslipidemia	6 week
Secondary	Serum Triglyceride	to assess dyslipidemia	6 weeks