Pharmacogenomic Decision Support With GeneSight Psychotropic to Guide the Treatment of Schizophrenia/Schizoaffective Disorder
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|ClinicalTrials.gov Identifier: NCT02573168|
Recruitment Status : Recruiting
First Posted : October 9, 2015
Last Update Posted : February 12, 2018
|Condition or disease||Intervention/treatment||Phase|
|Schizophrenia Schizoaffective Disorder||Genetic: GeneSight Psychotropic (GEN) Genetic: Enhanced-GeneSight Psychotropic (E-GEN) Other: Treatment as Usual (TAU)||Phase 4|
The primary objectives of this study are 1) to compare the efficacy of GEN to treatment as usual (TAU) in improving response to psychotropic treatment in patients suffering from schizophrenia/schizoaffective disorder; and 2) to validate the utility of the new CAMH markers and demonstrate the superior predictive capabilities and greater clinical utility of E-GEN as compared to GEN.
This study is designed as a three-arm multi-centre, double-blind (participants and raters), randomized controlled trial to compare the clinical and economic outcomes of GEN, E-GEN and TAU for patients suffering from schizophrenia/schizoaffective disorder. Participants will be randomized in a 1:1:1 ratio to each of the three treatment arms. Recruitment will be 27 months. Follow-up will be 12 months.
Subjects will complete short diagnostic interviews specific to their clinical diagnosis, basic metabolic measures (eg. blood pressure, weight), and provide buccal swab samples for genetic analysis (the unanalyzed buccal swabs and associated DNA will be biobanked). During the first visit, blood and urine samples will be required for laboratory panel screening and blood biobanking. Subjects will be monitored over a one year period and clinical measures and healthcare resource utilization will be obtained. Treating clinicians in the GEN and E-GEN arms will receive an easy to implement report providing pharmacogenomic guidance for prescribing psychotropic medications to their patients.
The study will recruit subjects from 10 sites, stratified into 2 clusters. Nine study sites altogether will form one of the two stratified clusters. CAMH will constitute the tenth study site and the second stratified cluster. The sample size required for this study was calculated using the expected change in PANSS, with a difference between treatment groups (GEN and E-GEN) and TAU of 0.5 standard deviation. Assuming intra class coefficient between clusters of 20%, statistical power of 90%, an alpha level of 0.05, and an expected drop-out rate of 42% by Week 12, a total of 531 subjects (i.e., 177 per treatment arm) are required to detect the same effect in this study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||531 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Outcomes Assessor)|
|Official Title:||A Three-arm, Parallel Group, Multicentre, Double-blind, Randomized Controlled Trial Evaluating the Impact of GeneSight Psychotropic and Enhanced-GeneSight Psychotropic, on Response to Psychotropic Treatment in Patients Suffering From Schizophrenia/Schizoaffective Disorder|
|Study Start Date :||November 2015|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||September 2020|
Experimental: GeneSight Psychotropic (GEN)
The GeneSight Psychotropic (GEN) product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection. More specifically, patients are tested for clinically important genetic variants of multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to metabolize, tolerate or respond to medications.
Genetic: GeneSight Psychotropic (GEN)
Patient DNA will be collected for all subjects and measured for variations in drug target genes and in drug metabolizing genes.Recommendations for optimal choices and dose adjustments for the 33 most commonly prescribed antidepressant and antipsychotic medications will be provided to subjects randomized to the GEN arm. This pharmacogenomic-based interpretive report will be provided to treating clinicians of patients in the GEN arm of the study, allowing clinicians to use the report to support their treatment decisions.
Experimental: Enhanced-GeneSight Psychotropic (E-GEN)
The current GEN test lacks predictive genes for antipsychotic-induced weight gain (AIWG), a major complication of antipsychotic drug use. Therefore, the Enhanced-GeneSight Psychotropic (E-GEN), which is an enhanced version of the GEN test, was developed by incorporating 6 new genes (represented by 7 SNPs) that are predictive for AIWG, to those used in the GEN algorithm. An increasing risk level associated with AIWG is estimated by an increasing number of risk genotypes that a given patient possesses among the 7 SNPs.
Genetic: Enhanced-GeneSight Psychotropic (E-GEN)
The E-GEN test incorporates into the existing GEN product new markers that are predictive of side effect of antipsychotic-induced weight gain (AIWG). The pharmacogenomic-based interpretive report from E-GEN will be provided to treating clinicians of patients in the E-GEN arm of the study, allowing clinicians to use the report to support their treatment decisions.
Active Comparator: Treatment as Usual (TAU)
The comparator chosen for this study provides a "real world" comparison of standard of care for patients who receive no pharmacogenomics guidance.
Patients randomized to the TAU arm will also have their DNA collected and a pharmacogenomic-based interpretive report will be generated using GEN testing. However, this report will not be shared with the treating clinicians until completion at 12 months of the study. Therefore, patients in this arm will receive clinical treatment as usual, without the use or knowledge of genotyping results by their treating clinicians.
Other: Treatment as Usual (TAU)
Subjects randomized to the TAU arm will also require collection of patient DNA. A pharmacogenomic-based interpretive report will be generated from GEN, however, this report is not provided to the treating clinician until completion of the study.
- Change in schizophrenic symptoms as assessed by the Positive and Negative Syndrome Scale (PANSS) [ Time Frame: From baseline to Week 12 ]Mean change in the PANSS score from baseline to Week 12 of the study
- Time between baseline and discontinuation of treatment for any cause [ Time Frame: Baseline, Weeks 8 and 12, Months 6 and 12 ]
- Change in severity of illness as assessed by the Clinical Global Impression of Severity (CGI-S) [ Time Frame: Baseline, Week 12, Months 6 and 12 ]
- Change in global improvement as assessed by Clinical Global Impression of Improvement (CGI-I) [ Time Frame: Week 12, Months 6 and 12 ]
- Change in global therapeutic benefit and global severity of side effects as assessed by Clinical Global Impression Efficacy Index (CGI-EI) [ Time Frame: Week 12, Months 6 and 12 ]
- Changes to initial prescribing based on availability of pharmacogenomic data [ Time Frame: Screening and Baseline ]
- Response rates to psychotropic medication [ Time Frame: Baseline, Weeks 8 and 12, Months 6 and 12 ]A responder is defined as a participant with 20% decrease in PANSS score from baseline.
- Time to response [ Time Frame: Baseline, Weeks 8 and 12, Months 6 and 12 ]
- Change in psychotropic medication side effects as assessed by the Udvalg for Kliniske Undersogeler (UKU) Side Effect Rating Scale [ Time Frame: Baseline, Weeks 8 and 12, Months 6 and 12 ]
- Change in severity of dyskinesias as assessed by the Abnormal Involuntary Movement Scale (AIMS) [ Time Frame: Baseline and Month 12 ]
- Weight gain [ Time Frame: Baseline, Weeks 8 and 12, Months 6 and 12 ]Subject's weight
- Waist-to-hip ratio [ Time Frame: Baseline, Weeks 8 and 12, Months 6 and 12 ]Subject's waist and hip measurements
- Change in health related quality of life as assessed by the EuroQol (EQ-5D-5L) [ Time Frame: Baseline, Week 12, Months 6 and 12 ]
- Change in health related quality of life as assessed by the Short Form (36) Health Survey (SF-36) [ Time Frame: Baseline, Week 12, Months 6 and 12 ]
- Pharmacogenetics in Psychiatry Follow-Up Questionnaire (PIP-FQ) [ Time Frame: Baseline, when prescription changes are made (expected average of every 4 weeks), Months 6 and 12 ]The PIPFQ is a questionnaire developed by CAMH to evaluate each physician's attitude and experience to pharmacogenomic testing. Information is solicited from the physician on three different domains: the processing of the physician's last referral, the contact and outcome of the physician's patient, and the physician's perspective on the future of genetic studies in psychiatric drug treatment.
- Healthcare resource utilization (Composite measure of healthcare costs): physician visits, hospital utilization, emergency department visits, medication use, and laboratory tests [ Time Frame: Baseline, Weeks 8 and 12, Months 6 and 12 ]
- Productivity losses (measured as economic costs) [ Time Frame: Baseline, Weeks 8 and 12, Months 6 and 12 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02573168
|Contact: James Bowen, BScPhm, MSc||905-522-1155 ext email@example.com|
|Centre for Addiction and Mental Health||Recruiting|
|Toronto, Ontario, Canada, M6J 1H4|
|Contact: Ofer Agid, M.D 4165358501 ext 34862 firstname.lastname@example.org|
|Principal Investigator: Ofer Agid, M.D|
|Sub-Investigator: Daniell Mueller, M.D|
|Sub-Investigator: Gary Remington, M.D|
|Study Chair:||Jean-Eric Tarride, PhD||St.Joseph's Healthcare, Hamilton/Mcmaster University|
|Principal Investigator:||James L Kennedy, MD||Centre for Addiction and Mental Health|
|Principal Investigator:||C Anthony Altar, PhD||Assurex Health Inc.|