Relative Effectiveness of Schizophrenia Therapy Study - Full Text View

Purpose

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.

Condition	Intervention
Schizophrenia Bipolar Disorder	Genetic: SULT4A1-1 genetic test

Study Type:	Observational
Official Title:	Relative Effectiveness of Schizophrenia Therapy (REST) Study

Resource links provided by NLM:

MedlinePlus related topics: Bipolar Disorder Mental Disorders Schizophrenia

U.S. FDA Resources

Further study details as provided by Medco Health Solutions, Inc.:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

One milliliter of saliva will be self collected by study subjects for genetic testing.

Enrollment:	1110
Study Start Date:	December 2010
Study Completion Date:	December 2012
Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Schizophrenia Patient with schizophrenia	Genetic: SULT4A1-1 genetic test SULT4A1-1 haplotype result (+/-)
Bipolar Patient with bipolar disorder	Genetic: SULT4A1-1 genetic test SULT4A1-1 haplotype result (+/-)

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Adults (≥18y/o) with either a schizophrenia or bipolar disorder diagnosis and were/are new to therapy for olanzapine, risperidone, quetiapine or ziprasidone.

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01245348

Locations

United States, New Jersey
Medco Health Solutions, Inc.
Franklin Lakes, New Jersey, United States, 07417

Sponsors and Collaborators

Medco Health Solutions, Inc.

SureGene, LLC

Investigators

Principal Investigator:

Kelly Parsons, Ph.D.

Medco Health Solutions, Inc.

More Information

Publications:

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.

Responsible Party:	Kelly Parsons, Senior Research Manager, Medco Health Solutions, Inc.
ClinicalTrials.gov Identifier:	NCT01245348 History of Changes
Other Study ID Numbers:	REST
Study First Received:	November 18, 2010
Last Updated:	February 22, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by Medco Health Solutions, Inc.:

Schizophrenia
Bipolar Disorder
atypical antipsychotic
adherence

cost effectiveness
pharmacogenetics
mental illness
SULT4A1

Additional relevant MeSH terms:

Bipolar Disorder
Schizophrenia
Affective Disorders, Psychotic

Mood Disorders
Mental Disorders
Schizophrenia and Disorders with Psychotic Features

ClinicalTrials.gov processed this record on June 13, 2013

Relative Effectiveness of Schizophrenia Therapy Study (REST)