Relative Effectiveness of Schizophrenia Therapy Study

Brief Summary

Official Title: “Relative Effectiveness of Schizophrenia Therapy (REST) Study”

The purpose of this study is to validate that SULT4A1-1 status stratification improves responses to atypical antipsychotics in schizophrenia and to extend these findings into bipolar disorder.

  • Study Type: Observational
  • Study Design: N/A
  • Study Primary Completion Date: December 2012

Detailed Clinical Trial Description

The total economic burden for schizophrenia (SZ) in the U.S. is estimated to be more than $60 billion annually. A large contributor to the economic burden of this and other chronic mental disorders, including bipolar disorder (BPD), is the exacerbation of symptoms and disability due to lack of drug efficacy. For these disorders, clinicians typically choose a first line antipsychotic therapy without the support of a diagnostic tool; often, patients are switched to another drug after less than six months of treatment due to what is perceived by patients and clinicians as both insufficient efficacy and unacceptable side effects.

Originally, the sulfotransferase family 4A, member 1 (SULT4A1) gene was selected as a biomarker of interest in SZ based on results showing associations between the gene and disease severity. Later on, SULT4A1 gene status was also associated with better efficacy of atypical antipsychotic (e.g. Zyprexa® (olanzapine) and Risperdal® (risperidone)), with respect to both time to discontinuation and quantitative measures of clinical improvement.

In this prospectively designed, non-randomized retrospective study, we will recruit and genotype subjects with schizophrenia or bipolar disorder that were/are new to therapy for any of the four drugs under evaluation. By looking at retrospective and prospective longitudinal medical and pharmacy data stored within the integrated claims database, we will validate the association of the SULT4A1 gene to the efficacy of selected atypical antipsychotic therapies.

Interventions Used in this Clinical Trial

  • Genetic: SULT4A1-1 genetic test
    • SULT4A1-1 haplotype result (+/-)

Arms, Groups and Cohorts in this Clinical Trial

  • Schizophrenia
    • Patient with schizophrenia
  • Bipolar
    • Patient with bipolar disorder

Outcome Measures for this Clinical Trial

Primary Measures

  • Assess differences in time to discontinuation (TTD) of olanzapine and risperidone therapy between schizophrenia and bipolar disorder subjects (independently) who are SULT4A1-1 haplotype-positive and who are SULT4A1-1 haplotype-negative
    • Time Frame: 1 year
      Safety Issue?: No

Secondary Measures

  • Assess differences in time to discontinuation (TTD) of quetiapine and ziprasidone therapy between schizophrenia and bipolar disorder subjects (independently) who are SULT4A1-1 haplotype-positive and who are SULT4A1-1 haplotype-negative
    • Time Frame: 1 year
      Safety Issue?: No
  • For each drug under study assess hospitalization rates for psychiatric illness between schizophrenia and bipolar disorder subjects (independently) who are SULT4A1-1 haplotype-positive and who are SULT4A1-1 haplotype-negative
    • Time Frame: 1 year
      Safety Issue?: No
  • Evaluate whether there are differences in time to discontinuation (TTD) of each drug under study between schizophrenia and bipolar disorder subjects (combined) who are SULT4A1-1 haplotype-positive and who are SULT4A1-1 haplotype-negative
    • Time Frame: 1 year
      Safety Issue?: No
  • Evaluate whether there are differences in overall medical spending between schizophrenia and bipolar disorder subjects (independently and combined) who are SULT4A1-1 haplotype-positive and who are SULT4A1-1 haplotype-negative for each drug under study
    • Time Frame: 1 year
      Safety Issue?: No
  • Evaluate whether there are differences in adherence to each drug under study between schizophrenia and bipolar disorder subjects (independently and combined) who are SULT4A1-1 haplotype-positive and who are SULT4A1-1 haplotype-negative
    • Time Frame: 1 year
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

Inclusion Criteria

  • Subjects ≥ 18 years of age
  • Subjects with either a confirmed diagnosis of schizophrenia or bipolar disorder or subjects with self reported schizophrenia or bipolar disorder
  • Subjects who were/are new to therapy for olanzapine, risperidone, quetiapine or ziprasidone
  • Subjects who are willing and able to provide informed consent

Exclusion Criteria

  • Subjects initially prescribed less than the generally accepted minimally effective dose of the drugs under study
  • Subjects with Major Depressive Disorder (MDD) or another psychotic disorder other than schizophrenia or bipolar disorder
  • Subjects with catatonic schizophrenia
  • Subjects with moderate to severe mental retardation
  • Subjects that refuse to participate in the study

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • Medco Health Solutions, Inc.
  • Collaborator
    • SureGene, LLC
  • Provider of Information About this Clinical Study
    • Principal Investigator: Kelly Parsons, Senior Research Manager – Medco Health Solutions, Inc.
  • Overall Official(s)
    • Kelly Parsons, Ph.D., Principal Investigator, Medco Health Solutions, Inc.

References

Nasrallah HA. The case for long-acting antipsychotic agents in the post-CATIE era. Acta Psychiatr Scand. 2007 Apr;115(4):260-7. Review.

Stroup TS, McEvoy JP, Swartz MS, Byerly MJ, Glick ID, Canive JM, McGee MF, Simpson GM, Stevens MC, Lieberman JA. The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development. Schizophr Bull. 2003;29(1):15-31.

Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK; Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005 Sep 22;353(12):1209-23. Epub 2005 Sep 19.

Sullivan PF, Lin D, Tzeng JY, van den Oord E, Perkins D, Stroup TS, Wagner M, Lee S, Wright FA, Zou F, Liu W, Downing AM, Lieberman J, Close SL. Genomewide association for schizophrenia in the CATIE study: results of stage 1. Mol Psychiatry. 2008 Jun;13(6):570-84. Epub 2008 Mar 18. Erratum in: Mol Psychiatry. 2009 Dec;14(12):1144.

Liyou NE, Buller KM, Tresillian MJ, Elvin CM, Scott HL, Dodd PR, Tannenberg AE, McManus ME. Localization of a brain sulfotransferase, SULT4A1, in the human and rat brain: an immunohistochemical study. J Histochem Cytochem. 2003 Dec;51(12):1655-64.

Minchin RF, Lewis A, Mitchell D, Kadlubar FF, McManus ME. Sulfotransferase 4A1. Int J Biochem Cell Biol. 2008;40(12):2686-91. Epub 2007 Dec 3. Review.

Hildebrandt MA, Carrington DP, Thomae BA, Eckloff BW, Schaid DJ, Yee VC, Weinshilboum RM, Wieben ED. Genetic diversity and function in the human cytosolic sulfotransferases. Pharmacogenomics J. 2007 Apr;7(2):133-43. Epub 2006 Jun 27.

Lewis AG, Minchin RF. Lack of exonic sulfotransferase 4A1 mutations in controls and schizophrenia cases. Psychiatr Genet. 2009 Feb;19(1):53-5.

Brennan MD, Condra J. Transmission disequilibrium suggests a role for the sulfotransferase-4A1 gene in schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2005 Nov 5;139B(1):69-72.

Condra JA, Neibergs H, Wei W, Brennan MD. Evidence for two schizophrenia susceptibility genes on chromosome 22q13. Psychiatr Genet. 2007 Oct;17(5):292-8.

Meltzer HY, Brennan MD, Woodward ND, Jayathilake K. Association of Sult4A1 SNPs with psychopathology and cognition in patients with schizophrenia or schizoaffective disorder. Schizophr Res. 2008 Dec;106(2-3):258-64. Epub 2008 Sep 27.

Leucht S, Arbter D, Engel RR, Kissling W, Davis JM. How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials. Mol Psychiatry. 2009 Apr;14(4):429-47. Epub 2008 Jan 8. Review.

Wu EQ, Birnbaum HG, Shi L, Ball DE, Kessler RC, Moulis M, Aggarwal J. The economic burden of schizophrenia in the United States in 2002. J Clin Psychiatry. 2005 Sep;66(9):1122-9.

Ascher-Svanum H, Zhu B, Faries D, Landbloom R, Swartz M, Swanson J. Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia. BMC Psychiatry. 2006 Feb 21;6:8.

Source

Clinical Trials content is provided directly by the US National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of information about a specific clinical trial contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01245348