Prospective Pharmacogenetic Testing and Clinical Outcomes in Patients With Early-Phase Psychosis

This study evaluates whether prospective pharmacogenetic testing is cost-effective in affecting clinical treatment outcomes in patients with early-phase psychosis.

Study Overview

• Status: Completed
• Conditions: Psychotic Disorders; Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder; Bipolar Disorder
• Intervention / Treatment: Biological: PGx testing guided treatment (PGT)

Detailed Description

Large scale clinical trials have demonstrated that a substantial proportion of patients with psychotic disorders, such as schizophrenia and bipolar disorder, discontinue their antipsychotic medications due to either lack of efficacy or intolerable side effects, such as extrapyramidal symptoms (EPS) and weight gain. In clinical practice, it is essentially a trial and error process in deciding the best antipsychotic drug to start or switch to after a failed trial as there is little empirical data available to guide clinicians in drug selection. One promising tool, which can potentially provide valuable information to help guide medication management, is pharmacogenetic testing of certain genetic variants that are associated with psychiatric drug response. However, most pharmacogenetic studies to date have been retrospective, and there is no prospective clinical trial evaluating the clinical utility of pharmacogenetic testing in guiding clinical practice. Furthermore, it is unknown whether pharmacogenetic testing is cost effective.

Until recently, pharmacogenetic testing has been expensive and time-consuming. New technology in the past few years makes it possible for cheaper and faster testing. One of the companies that offer pharmacogenetic testing services, Genomind LLC, provides genotyping of variants (GeneceptTM Assay) that are relevant to psychiatric drug response. For example, the serotonin 2C receptor gene (HTR2C) has variants that protect patients from antipsychotic drug induced weight gain (-759C/T, rs3813929); a deletion variant of the dopamine D2 receptor gene (DRD2) suggests poor efficacy with antipsychotic drug treatment (-141C Ins/Del, rs1799732); the short allele of the serotonin transporter gene (SLC6A4) is associated with antidepressant side effects.

In the present study, investigators propose to conduct a prospective, randomized, rater-blinded clinical trial to test the clinical utility and cost-effectiveness of pharmacogenetic testing in guiding medication treatment in patients with recent-onset psychotic disorders. Patients will be assigned to either a pharmacogenetic testing guided treatment condition (PGT) or a treatment as usual condition (TAU). In the PGT condition, patients will utilize the GeneceptTM Assay and results will be provided to their prescribers who may use the results to guide medication management. In the TAU condition, patients will also utilize the GeneceptTM Assay but the results will not be provided back to their prescribers, who will treat the patients without the knowledge of pharmacogenetic testing results.

Pharmacogenetic testing may be more relevant in recent-onset or early stage illnesses because past medication history that is typically used to guide medication choice may not be available. Pharmacogenomic testing may be particularly pertinent to younger patients because they tend to be medication naïve and do not have previous medication history to guide future treatment. Pharmacogenomic testing may provide valuable information to guide medication choice in clinical practice.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Glen Oaks, New York, United States, 11004
      • Zucker Hillside Hospital-North Shore Long Island Jewish Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 64 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 15-64;
2. Diagnostic and Statistical Manual Diploma in Social Medicine diagnosis of schizophrenia (DSM IV), schizoaffective disorder, schizophreniform disorder, psychotic disorder NOS, and bipolar disorder;
3. Onset of antipsychotic treatment within the past 3 years;
4. Able to provide informed consent. (assent for those under age 18)

Exclusion Criteria:

1. Evidence of serious medical conditions,
2. Female patients who are pregnant or breast feeding;
3. Patients who are not willing to take medications for treatment;
4. Patients who are unable to provide informed consent due to impairment in decision-making ability.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PGx testing guided treatment (PGT); Results of the GeneceptTM Assay will be provided to their prescribers who may use the knowledge to guide medication management.	Biological: PGx testing guided treatment (PGT); Genecept Assay (GeneceptTM Assay) will provide information on genotypes of genetic variants that are relevant to psychiatric drug response. The provider can use the information to decide on which psychotropic drugs to use.
No Intervention: Treatment as usual condition (TAU); Patients will also utilize the GeneceptTM Assay but the results will not be provided back to their prescribers, who will treat the patients without the knowledge of pharmacogenetic testing results.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Discontinuation of First Medication	Due to lack of efficacy or intolerability	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prescribing Behavior Change Based on the Results of the Pharmacogenetic Testing	The clinician is asked to fill out a questionnaire elaborating the medication decision-making process for each patient, including whether or not acting on the genetic information provided clinically relevant information.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Efficacy	Assessed by Brief Psychiatric Rating Scale (BPRS)	12 months
Adverse Drug Response	Assessed by measures including Hillside Adverse Events Rating Scale (HAERS), Simpson-Angus Rating Scale for Extrapyramidal Symptoms (SARSES), Barnes Rating Scale for Drug-Induced Akathisia (BRSDIA), Abnormal Involuntary Movement Scale (AIMS)	12 months
Treatment Services Utilized	Examine overall medical costs (including outpatient visits, procedures, hospitalizations, other professional charges, laboratory charges, and medication costs), as well as costs specifically associated with treatment of psychiatric symptoms based upon ICD9 code (for procedures and visits) and medication category. This information will be provided by insurance company for patients with ValueOptions insurance coverage.	12 months

Collaborators and Investigators

• Sponsor: Northwell Health
• Collaborators: Genomind, LLC
• Investigators: Principal Investigator: Jianping Zhang, MD, PhD, Psychiatrist

Publications and helpful links

General Publications

• Malhotra AK, Zhang JP, Lencz T. Pharmacogenetics in psychiatry: translating research into clinical practice. Mol Psychiatry. 2012 Jul;17(8):760-9. doi: 10.1038/mp.2011.146. Epub 2011 Nov 15.
• Zhang JP, Malhotra AK. Pharmacogenetics and antipsychotics: therapeutic efficacy and side effects prediction. Expert Opin Drug Metab Toxicol. 2011 Jan;7(1):9-37. doi: 10.1517/17425255.2011.532787.

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2014
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: September 30, 2015
• First Submitted That Met QC Criteria: September 30, 2015
• First Posted (Estimate): October 1, 2015

Study Record Updates

• Last Update Posted (Actual): January 24, 2018
• Last Update Submitted That Met QC Criteria: January 22, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Bipolar and Related Disorders; Schizophrenia; Disease; Psychotic Disorders; Mental Disorders; Bipolar Disorder
• Other Study ID Numbers: 13-587B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO