Pharmacogenomic Decision Support With GeneSight Psychotropic to Guide the Treatment With Antipsychotics

NCT02573168 | Completed DMC

• 1 other identifier: EXCITE-013304-ARX1010.PTL
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

Antipsychotics are approved to treat several conditions, including Schizophrenia, Schizoaffective Disorder, Bipolar Disorder, and Major Depressive Disorder among others. The typical and atypical antipsychotics, derive their therapeutic benefit predominantly from the antagonism of dopamine D2 and 5-HT2A receptors. Many of these compounds are associated with common and significant adverse effects (e.g. weight gain, extrapyramidal symptoms, hyperprolactinemia, sexual dysfunction, and cardiac effects) which negatively impact on adherence. Today, antipsychotic induced weight gain (AIWG) is a leading cause for antipsychotic discontinuation. Importantly as well, approximately 20-30% of all patients with schizophrenia do not respond adequately to an initial antipsychotic trial, and strikingly, 83% of those who go on to a second antipsychotic trial do not meet criteria for response. To-date, no RCT has been conducted to evaluate the outcomes in patients taking antipsychotics following the use of pharmacogenomic guidance of treatment selections. Therefore, the rationale for this trial is to utilize a double-blinded RCT design to evaluate and compare the clinical outcomes in participants treated with the benefit of GEN and E-GEN testing. Furthermore, this trial also intends to develop an evidence- based case for the value of GEN and E-GEN to Canadian health-care payers.

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

Pharmacogenomic; Pharmacogenomic Testing; Pharmacogenomics; Genetic Testing; Genetics; GeneSight; Enhanced GeneSight; Psychotropic

Outcome Measures

Primary Outcomes (2)

• Change in patients' weight and waist-to-hip ratio

  Mean change in patients' weight and waist-to-hip ratio from baseline and week 12 of the study

  From baseline to week 12

• Change in schizophrenic symptoms as assessed by the Positive and Negative Syndrome

  Mean change in the PANSS score from baseline to Week 12 of the study

  From baseline to Week 12

Secondary Outcomes (14)

• Time between baseline and discontinuation of treatment for any cause

  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)

  Baseline, Week 12, Months 6 and 12

• Change in global improvement as assessed by Clinical Global Impression of Improvement (CGI-I)

  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)

  Week 12, Months 6 and 12

• Changes to initial prescribing based on availability of pharmacogenomic data

  Screening and Baseline

Study Arms (3)

GeneSight Psychotropic (GEN)

EXPERIMENTAL

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)

Enhanced-GeneSight Psychotropic (E-GEN)

EXPERIMENTAL

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)

Treatment as Usual (TAU)

ACTIVE COMPARATOR

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)

Interventions

GeneSight Psychotropic (GEN) GENETIC

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.

GeneSight Psychotropic (GEN)

Enhanced-GeneSight Psychotropic (E-GEN) GENETIC

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.

Enhanced-GeneSight Psychotropic (E-GEN)

Treatment as Usual (TAU) OTHER

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.

Treatment as Usual (TAU)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older;
• Suffer from schizophrenia, schizoaffective disorder, schizophreniform disorder, psychosis not otherwise specified, bipolar disorder (I, II, NOS) or major depressive disorder meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria;
• Have moderate to severe psychiatric symptoms;
• Intending to switch to, or start a new antipsychotic medication;:
• Be capable and willing to provide written informed consent to participate in this study;
• Agree to abide by the study protocol and its restrictions and be able to complete all aspects of the study, including all visits and tests.

You may not qualify if:

• Patients posing a serious suicidal risk and/or violence as judged by the investigator;
• Patients with a current Axis I diagnosis of:
• Delirium
• Dementia
• Amnestic and other cognitive disorder;
• Patients who are on restricted diets (e.g., diabetes), who have an eating restriction disorder (e.g., bulimia, anorexia), or who are undergoing weight-reducing interventions (e.g. metformin, or structured diet program).
• Patients with a history of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic or euthyroid for 6 months;
• Patients who meet DSM-IV-TR criteria for any significant current substance dependence;
• Patients with:
• hepatic insufficiency (three times the upper limit of normal (ULN) for aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)); liver transplant recipient; cirrhosis of the liver;
• malignancy (except basal cell carcinoma) and/or chemotherapy within 1 year prior to screening; malignancy more than 1 year prior to screening must have been local and without metastasis and/or recurrence, and if treated with chemotherapy, without nervous system complications;
• significant unstable medical condition or life threatening disease with anticipated survival of less than 6 months;
• need for therapies that may obscure the results of treatment and/or of the study
• Participation in another clinical trial within 30 days of the screening visit;
• Anticipated inability to attend scheduled study visits;

Sponsors & Collaborators

• St. Joseph's Healthcare Hamilton: lead
• Programs for Assessment of Technology in Health Research Institute: collaborator
• Centre for Addiction and Mental Health: collaborator
• Genome Canada: collaborator
• AssureRx Canada Ltd: collaborator
• Assurex Health Inc.: collaborator
• Mars Excellence in Clinical Innovation and Technology Evaluation: collaborator

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H4, Canada

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Jean-Eric Tarride, PhD

  St.Joseph's Healthcare, Hamilton/Mcmaster University

  STUDY CHAIR

• James L Kennedy, MD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

• Bryan Dechairo, PhD

  Assurex Health Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: October 8, 2015
• First Posted: October 9, 2015
• Study Start: January 1, 2016
• Primary Completion: July 1, 2019
• Study Completion: September 1, 2020
• Last Updated: November 19, 2020

Record last verified: 2020-11

Locations

CA (1)