NCT02466477

Brief Summary

Evidence exists supporting the ability of genetic variations to influence patient drug response and side effects. Previous studies utilizing an open-label design have shown significant improvement in major depressive disorder (MDD) patient outcomes following use of the GeneSight Psychotropic (GEN) test. The first objective of this trial is to utilize a double-blinded, randomized clinical trial design to replicate previous findings of improvement in clinical outcomes in MDD subjects whose medication therapy was guided by GEN testing. Another objective is to determine the added benefit of Enhanced-GeneSight (E-GEN) compared to GEN for the pharmacogenomic guidance of treatment selections. Furthermore, this trial intends to develop an evidence-based case for the value of GEN and E-GEN to Canadian healthcare payers.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
542

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jun 2015

Longer than P75 for phase_4

Geographic Reach
1 country

14 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2015

Completed
2 days until next milestone

First Submitted

Initial submission to the registry

June 3, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

June 9, 2015

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2018

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2019

Completed
Last Updated

April 30, 2020

Status Verified

April 1, 2020

Enrollment Period

3.4 years

First QC Date

June 3, 2015

Last Update Submit

April 28, 2020

Conditions

Depressive Disorder, MajorDepressionDepressive Disorder

Keywords

PharmacogenomicPharmacogenomic TestingPharmacogenomicsGenetic TestingGeneticsMajor Depressive DisorderGeneSightEnhanced GeneSightPsychotropic

Outcome Measures

Primary Outcomes (1)

  • Change in depressive symptoms as assessed by the 17-item Hamilton Depression (HAM-D17) score

    Mean change in the 17-item Hamilton Depression (HAM-D17) score from baseline to Week 8 of the study

    From baseline to Week 8

Secondary Outcomes (20)

  • Change in depressive symptoms as assessed by the 16-Item Clinician Quick Inventory of Depressive Symptomatology (QIDS-SR16)

    Baseline, Weeks 8 and 12, and Month 12

  • Change in depressive symptoms as assessed by the 9-Item Patient Health Questionnaire (PHQ-9)

    Baseline, Weeks 8 and 12, and Month 12

  • Change in anxiety symptoms as assessed by theGeneralized Anxiety Disorder 7-Item (GAD-7) Scale

    Baseline, Weeks 8 and 12, and Month 12

  • Change in severity of illness as assessed by the Clinical Global Impression of Severity (CGI-S)

    Baseline, Week 12 and Month 12

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

    Week 12, and Month 12

  • +15 more secondary outcomes

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

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • years of age or older;
  • Suffer from a Major Depressive Episode meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria;
  • Have had an inadequate response within the current episode to at least one psychotropic treatment in GEN. Inadequate response is defined as inadequate efficacy after 6 weeks of a psychotropic treatment or discontinuation of a psychotropic treatment due to adverse events (AEs) or intolerability;
  • Have each a score on the 16-item Clinician Quick Inventory of Depressive Symptomatology (QIDS-C16) and 16-item Self-Report Quick Inventory of Depressive Symptomatology (QIDS-SR16) rating scales ≥ 11;
  • Be able to understand the requirements of the study and 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 in need of immediate hospitalization as judged by the Investigator;
  • Patients with a diagnosis of Bipolar I or II disorder;
  • Patients with a current Axis I diagnosis of:
  • Delirium
  • Dementia
  • Amnestic and/or other cognitive disorder
  • Schizophrenia or other psychotic disorder;
  • Patients having experienced hallucinations, delusions, or any psychotic symptomatology within the current depressive episode or during prior depressive episodes;
  • Patient is currently in an inpatient facility;
  • Patients with a history of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic or euthyroid for at least 6 months;
  • Patients who meet DSM-IV-TR criteria for any significant current substance use disorder;
  • 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 - need for therapies that may obscure the results of treatment and/or of the study;
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

Chatham-Kent Clinical Trials Research Center

Chatham, Ontario, N7L 1B7, Canada

Location

Hamilton Community Health Centre Family Health Organization

Hamilton, Ontario, L8L 5G8, Canada

Location

Hamilton Medical Research Group

Hamilton, Ontario, L8M 1K7, Canada

Location

St. Joseph's Healthcare Hamilton (SJHH)

Hamilton, Ontario, L8N 3K7, Canada

Location

Milestone Research

London, Ontario, N5W6A2, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Parkwood Institute, London

London, Ontario, N6C 0A7, Canada

Location

Hopital Montfort

Ottawa, Ontario, K1K0T2, Canada

Location

Thornhill Medical Centre

Thornhill, Ontario, L4J 1E9, Canada

Location

Canadian Phase Onward Inc.

Toronto, Ontario, M3J 2C5, Canada

Location

Women's College Hospital

Toronto, Ontario, M5S 1B2, Canada

Location

Sinai Health System

Toronto, Ontario, M5T 3L9, Canada

Location

Centre for Addiction and Mental Health (CAMH)

Toronto, Ontario, M6J 1H4, Canada

Location

Manna Research

Toronto, Ontario, M9W 4L6, Canada

Location

Related Publications (1)

  • Tiwari AK, Zai CC, Altar CA, Tanner JA, Davies PE, Traxler P, Li J, Cogan ES, Kucera MT, Gugila A, Braganza N, Emmerson H, Zai G, Muller DJ, Levitan R, Kloiber S, Daskalakis ZJ, Frey BN, Bowen JM, Tarride JE, Tytus R, Chandrasena R, Voudouris N, Taylor VH, Tempier R, Sharma V, Vasudev A, Dzongowski P, Pliamm L, Greenspoon T, Dechairo BM, Kennedy JL. Clinical utility of combinatorial pharmacogenomic testing in depression: A Canadian patient- and rater-blinded, randomized, controlled trial. Transl Psychiatry. 2022 Mar 14;12(1):101. doi: 10.1038/s41398-022-01847-8.

    PMID: 35288545DERIVED

MeSH Terms

Conditions

Depressive Disorder, MajorDepressionDepressive Disorder

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Mood DisordersMental DisordersBehavioral SymptomsBehavior

Study Officials

  • 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
phase 4
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Sponsor

Study Record Dates

First Submitted

June 3, 2015

First Posted

June 9, 2015

Study Start

June 1, 2015

Primary Completion

November 1, 2018

Study Completion

September 1, 2019

Last Updated

April 30, 2020

Record last verified: 2020-04

Locations

CA(14)