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

NCT03304457 | Completed Phase 4

• 1 other identifier: T/IM-F/17-18/29
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Schizophrenia

Keywords

Lurasidone; Olanzapine; Brain derived neurotrophic factor; Nerve growth factor; Neurotrophin 3

Outcome Measures

Primary Outcomes (1)

• Serum brain derived neurotrophic factor (BDNF)

  the change in serum level of BDNF from baseline after treatment with lurasidone or olanzapine

  6 weeks

Secondary Outcomes (13)

• serum nerve growth factor (NGF)

  6 weeks

• Serum Neurotrophin 3 (NT3)

  6 weeks

• PANSS score

  6 weeks

• Social and occupational functioning assessment scale (SOFAS)

  6 weeks

• Serum hsCRP

  6 weeks

Study Arms (2)

Olanzapine

ACTIVE COMPARATOR

Olanzapine will be prescribed at a dose of 10mg once daily orally for 6 weeks

Drug: Olanzapine

Lurasidone

EXPERIMENTAL

Lurasidone will be prescribed at a dose of 80mg/day once daily orally for 6 weeks

Drug: Lurasidone

Interventions

Olanzapine DRUG

Olanzapine 10mg once daily orally for 6 weeks

Olanzapine

Lurasidone DRUG

Lurasidone 80mg once daily orally for 6 weeks

Lurasidone

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• All India Institute of Medical Sciences, Bhubaneswar: lead

Study Sites (1)

AIIMS

Bhubaneshwar, Odisha, 751019, India

Location

Related Publications (14)

• 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.

  PMID: 18791076 RESULT

• 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.

  PMID: 21639796 RESULT

• 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.

  PMID: 21357874 RESULT

• Ashe PC, Berry MD, Boulton AA. Schizophrenia, a neurodegenerative disorder with neurodevelopmental antecedents. Prog Neuropsychopharmacol Biol Psychiatry. 2001 May;25(4):691-707. doi: 10.1016/s0278-5846(01)00159-2.

  PMID: 11383973 RESULT

• Perez-Neri I, Ramirez-Bermudez J, Montes S, Rios C. Possible mechanisms of neurodegeneration in schizophrenia. Neurochem Res. 2006 Oct;31(10):1279-94. doi: 10.1007/s11064-006-9162-3. Epub 2006 Sep 28.

  PMID: 17006758 RESULT

• 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. doi: 10.1093/schbul/sbl004. Epub 2006 Jul 7.

  PMID: 16829550 RESULT

• 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 28.

  PMID: 25681004 RESULT

• 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 first episode untreated schizophrenic patients. World J Biol Psychiatry. 2010 Mar;11(2 Pt 2):256-61. doi: 10.3109/15622970802309617.

  PMID: 20218790 RESULT

• 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-derived neurotrophic factor (BDNF) levels in schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Jun 30;31(5):1072-7. doi: 10.1016/j.pnpbp.2007.03.010. Epub 2007 Mar 24.

  PMID: 17459549 RESULT

• 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(1):21-7. doi: 10.1097/YIC.0b013e3280103593.

  PMID: 17159456 RESULT

• 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 schizophrenia patients. Psychopharmacology (Berl). 2014 Sep;231(18):3757-64. doi: 10.1007/s00213-014-3515-4. Epub 2014 Mar 5.

  PMID: 24595507 RESULT

• Gonzalez-Pinto A, Mosquera F, Palomino A, Alberich S, Gutierrez 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 Psychopharmacol. 2010 Jul;25(4):241-5. doi: 10.1097/yic.0b013e328338bc5a.

  PMID: 20568658 RESULT

• Jena M, Mishra A, Mishra BR, Nath S, Maiti R. Effect of lurasidone versus olanzapine on cardiometabolic parameters in unmedicated patients with schizophrenia: a randomized controlled trial. Psychopharmacology (Berl). 2020 Nov;237(11):3471-3480. doi: 10.1007/s00213-020-05628-3. Epub 2020 Aug 1.

  PMID: 32740676 DERIVED

• Jena M, Ranjan R, Mishra BR, Mishra A, Nath S, Sahu P, Meher BR, Srinivasan A, Maiti R. Effect of lurasidone vs olanzapine on neurotrophic biomarkers in unmedicated schizophrenia: A randomized controlled trial. J Psychiatr Res. 2019 May;112:1-6. doi: 10.1016/j.jpsychires.2019.02.007. Epub 2019 Feb 12.

  PMID: 30782512 DERIVED

MeSH Terms

Conditions

Schizophrenia; Hereditary Sensory and Autonomic Neuropathies

Interventions

Olanzapine; Lurasidone Hydrochloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Isoindoles

Study Officials

• Debasish Hota, MD, DM

  Professor & Head

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: A randomized, open label, active controlled study

Study Record Dates

• First Submitted: October 3, 2017
• First Posted: October 9, 2017
• Study Start: August 25, 2017
• Primary Completion: March 12, 2018
• Study Completion: March 25, 2018
• Last Updated: March 31, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)