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

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

Interventions

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.

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.

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.

Sponsors & Collaborators

• Programs for Assessment of Technology in Health Research Institute

  collaborator OTHER

• Centre for Addiction and Mental Health

  collaborator OTHER

• Genome Canada

  collaborator OTHER

• AssureRx Canada Ltd

  collaborator OTHER

• Assurex Health Inc.

  collaborator INDUSTRY

• Mars Excellence in Clinical Innovation and Technology Evaluation

  collaborator OTHER

• St. Joseph's Healthcare Hamilton

  lead OTHER

Principal Investigators

• Jean-Eric Tarride, PhD · St.Joseph's Healthcare, Hamilton/Mcmaster University

• James L Kennedy, MD · Centre for Addiction and Mental Health

• Bryan Dechairo, PhD · Assurex Health Inc.

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-01-31

Primary Completion

2019-07-31

Completion

2020-09-30

Countries

• Canada

Study Locations