Relative Effectiveness of Schizophrenia Therapy Study (REST)
Primary Purpose
Schizophrenia, Bipolar Disorder
Status
Completed
Phase
Locations
United States
Study Type
Observational
Intervention
SULT4A1-1 genetic test
Sponsored by
About this trial
This is an observational trial for Schizophrenia focused on measuring Schizophrenia, Bipolar Disorder, atypical antipsychotic, adherence, cost effectiveness, pharmacogenetics, mental illness, SULT4A1
Eligibility 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
Sites / Locations
- Medco Health Solutions, Inc.
Arms of the Study
Arm 1
Arm 2
Arm Type
Arm Label
Schizophrenia
Bipolar
Arm Description
Patient with schizophrenia
Patient with bipolar disorder
Outcomes
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
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
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
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
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
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
Full Information
NCT ID
NCT01245348
First Posted
November 18, 2010
Last Updated
February 22, 2013
Sponsor
Medco Health Solutions, Inc.
Collaborators
SureGene, LLC
1. Study Identification
Unique Protocol Identification Number
NCT01245348
Brief Title
Relative Effectiveness of Schizophrenia Therapy Study
Acronym
REST
Official Title
Relative Effectiveness of Schizophrenia Therapy (REST) Study
Study Type
Observational
2. Study Status
Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medco Health Solutions, Inc.
Collaborators
SureGene, LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Bipolar Disorder
Keywords
Schizophrenia, Bipolar Disorder, atypical antipsychotic, adherence, cost effectiveness, pharmacogenetics, mental illness, SULT4A1
7. Study Design
Enrollment
1110 (Actual)
Biospecimen Retention
Samples With DNA
Biospecimen Description
One milliliter of saliva will be self collected by study subjects for genetic testing.
8. Arms, Groups, and Interventions
Arm Title
Schizophrenia
Arm Description
Patient with schizophrenia
Arm Title
Bipolar
Arm Description
Patient with bipolar disorder
Intervention Type
Genetic
Intervention Name(s)
SULT4A1-1 genetic test
Intervention Description
SULT4A1-1 haplotype result (+/-)
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Study Population Description
Adults (≥18y/o) with either a schizophrenia or bipolar disorder diagnosis and were/are new to therapy for olanzapine, risperidone, quetiapine or ziprasidone.
Sampling Method
Non-Probability Sample
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kelly Parsons, Ph.D.
Organizational Affiliation
Medco Health Solutions, Inc.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medco Health Solutions, Inc.
City
Franklin Lakes
State/Province
New Jersey
ZIP/Postal Code
07417
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
17355516
Citation
Nasrallah HA. The case for long-acting antipsychotic agents in the post-CATIE era. Acta Psychiatr Scand. 2007 Apr;115(4):260-7. doi: 10.1111/j.1600-0447.2006.00982.x.
Results Reference
background
PubMed Identifier
12908658
Citation
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. doi: 10.1093/oxfordjournals.schbul.a006986.
Results Reference
background
PubMed Identifier
16172203
Citation
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. doi: 10.1056/NEJMoa051688. Epub 2005 Sep 19. Erratum In: N Engl J Med. 2010 Sep 9;363(11):1092-3.
Results Reference
background
PubMed Identifier
18347602
Citation
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. doi: 10.1038/mp.2008.25. Epub 2008 Mar 18. Erratum In: Mol Psychiatry. 2009 Dec;14(12):1144.
Results Reference
background
PubMed Identifier
14623933
Citation
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. doi: 10.1177/002215540305101209.
Results Reference
background
PubMed Identifier
18248844
Citation
Minchin RF, Lewis A, Mitchell D, Kadlubar FF, McManus ME. Sulfotransferase 4A1. Int J Biochem Cell Biol. 2008;40(12):2686-91. doi: 10.1016/j.biocel.2007.11.010. Epub 2007 Dec 3.
Results Reference
background
PubMed Identifier
16801938
Citation
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. doi: 10.1038/sj.tpj.6500404. Epub 2006 Jun 27.
Results Reference
background
PubMed Identifier
19125109
Citation
Lewis AG, Minchin RF. Lack of exonic sulfotransferase 4A1 mutations in controls and schizophrenia cases. Psychiatr Genet. 2009 Feb;19(1):53-5. doi: 10.1097/YPG.0b013e3283118776.
Results Reference
background
PubMed Identifier
16152568
Citation
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. doi: 10.1002/ajmg.b.30222.
Results Reference
background
PubMed Identifier
17728668
Citation
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. doi: 10.1097/YPG.0b013e3281ac2345.
Results Reference
background
PubMed Identifier
18823757
Citation
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. doi: 10.1016/j.schres.2008.08.029. Epub 2008 Sep 27.
Results Reference
background
PubMed Identifier
18180760
Citation
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. doi: 10.1038/sj.mp.4002136. Epub 2008 Jan 8.
Results Reference
background
PubMed Identifier
16187769
Citation
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. doi: 10.4088/jcp.v66n0906.
Results Reference
background
PubMed Identifier
16504026
Citation
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. doi: 10.1186/1471-244X-6-8.
Results Reference
background
Learn more about this trial
Relative Effectiveness of Schizophrenia Therapy Study
We'll reach out to this number within 24 hrs