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CompletedNCT03304457Updated Mar 31, 2020

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

A Phase 4 interventional study of Olanzapine and Lurasidone in Schizophrenia, sponsored by All India Institute of Medical Sciences, Bhubaneswar. Completed at 1 site in India. Open to participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2020-03-31.

Sponsored by All India Institute of Medical Sciences, Bhubaneswar · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
100
Allocation
Randomized
Ages
18 Years to 45 Years
Sex
All
01

Study 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.

Read the detailed 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

02

Conditions studied

  • Schizophrenia

Browse trials for

Keywords

  • Lurasidone
  • Olanzapine
  • Brain derived neurotrophic factor
  • Nerve growth factor
  • Neurotrophin 3
03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
100 participants (actual)

Study arms

  • Active comparator
    Olanzapine

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

    Drug: Olanzapine

  • Experimental
    Lurasidone

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

    Drug: Lurasidone

Interventions

  • DrugOlanzapine

    Olanzapine 10mg once daily orally for 6 weeks

  • DrugLurasidone

    Lurasidone 80mg once daily orally for 6 weeks

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What researchers measure

Primary outcomes

  1. Serum brain derived neurotrophic factor (BDNF)

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

    Time frame: 6 weeks

Secondary outcomes

  1. serum nerve growth factor (NGF)

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

    Time frame: 6 weeks

  2. Serum Neurotrophin 3 (NT3)

    the change in serum level of NT3 from baseline after treatment with lurasidone or olanzapine

    Time frame: 6 weeks

  3. PANSS score

    To determine the association (if any) between change in serum neurotrophic factor and PANSS score

    Time frame: 6 weeks

  4. 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

    Time frame: 6 weeks

  5. Serum hsCRP

    to assess cardiovascular risk in schizophrenia

    Time frame: 6 weeks

  6. Serum Insulin

    to assess insulin resistance

    Time frame: 6 weeks

  7. LDL/HDL ratio

    to assess dyslipidemia and cardiovascular risk

    Time frame: 6 weeks

  8. Fasting blood sugar

    to assess dysglycemia

    Time frame: 6 weeks

  9. Glycosylated Hemoglobin (HbA1c)

    to assess dysglycemia

    Time frame: 6 weeks

  10. High Density Lipoprotein (HDL)

    to assess dyslipidemia

    Time frame: 6 week

  11. Low Density Lipoprotein (LDL)

    to assess dyslipidemia

    Time frame: 6 week

  12. Very Low Density Lipoprotein (VLDL)

    to assess dyslipidemia

    Time frame: 6 week

  13. Serum Triglyceride

    to assess dyslipidemia

    Time frame: 6 weeks

06

Study locations

1 site
  • AIIMS
    Bhubaneshwar, Odisha 751019, India
07

References and documents

Publications

  • 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. PubMed 18791076 ↗
  • 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. PubMed 21639796 ↗
  • 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. PubMed 21357874 ↗
  • 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. PubMed 11383973 ↗
  • 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. PubMed 17006758 ↗
  • 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. PubMed 16829550 ↗
  • 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. PubMed 25681004 ↗
  • 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. PubMed 20218790 ↗
  • 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. PubMed 17459549 ↗
  • 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. PubMed 17159456 ↗
  • 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. PubMed 24595507 ↗
  • 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. PubMed 20568658 ↗
  • 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. PubMed 32740676 ↗
  • 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. Erratum In: J Psychiatr Res. 2020 Jul;126:141. doi: 10.1016/j.jpsychires.2019.11.019. PubMed 30782512 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03304457
Lead sponsor
All India Institute of Medical Sciences, Bhubaneswar
Responsible party
Dr. Monalisa Jena, M.D. (Assistant Professor, All India Institute of Medical Sciences, Bhubaneswar) — Principal investigator
First posted
Oct 9, 2017
Start date
Aug 25, 2017
Primary completion
Mar 12, 2018
Completion
Mar 25, 2018
Last update
Mar 31, 2020

Study contacts

Debasish Hota, MD, DM
study director · Professor & Head

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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