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Depressive Disorder, MajorPhase 4NCT02466477

Pharmacogenomic Decision Support With GeneSight Psychotropic to Guide the Treatment of Major Depressive Disorder

A Phase 4 study testing GeneSight Psychotropic (GEN), Enhanced-GeneSight Psychotropic (E-GEN) and Treatment as Usual (TAU) in people with Depressive Disorder, Major and Depression, run by Assurex Health Inc. at 14 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
GeneSight Psychotropic (GEN), Enhanced-GeneSight Psychotropic (E-GEN) and Treatment as Usual (TAU)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
542 participants
Where
14 sitesCanada
Study dates
Jun 2015to Sep 2019
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 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.

Who cannot join

  • 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
Show all 23Show fewer
  • 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;
  • Participation in another clinical trial within 30 days of the screening visit;
  • Anticipated inability to attend scheduled study visits;
  • Patients who in the judgment of the Investigator may be unreliable or uncooperative with the evaluation procedure outlined in this protocol;
  • Patients with a history of prior pharmacogenomic testing;
  • Any change in psychotropic medication (including change in dosage) between screening and baseline;
  • Patients currently receiving electroconvulsive therapy (ECT), deep brain stimulation (DBS) or transcranial magnetic stimulation (TMS) treatments, or currently scheduled to receive maintenance treatments of ECT, DBS, or TMS during the course of the study;
  • Patients who self-report to be pregnant or lactating;
  • Patients with a history of gastric bypass surgery.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

Canada14 sites
  • Chatham-Kent Clinical Trials Research Center

    Chatham, Ontario, N7L 1B7

  • Hamilton Community Health Centre Family Health Organization

    Hamilton, Ontario, L8L 5G8

  • Hamilton Medical Research Group

    Hamilton, Ontario, L8M 1K7

  • St. Joseph's Healthcare Hamilton (SJHH)

    Hamilton, Ontario, L8N 3K7

  • Milestone Research

    London, Ontario, N5W6A2

  • London Health Sciences Centre

    London, Ontario, N6A 5W9

  • Parkwood Institute, London

    London, Ontario, N6C 0A7

  • Hopital Montfort

    Ottawa, Ontario, K1K0T2

  • Thornhill Medical Centre

    Thornhill, Ontario, L4J 1E9

  • Canadian Phase Onward Inc.

    Toronto, Ontario, M3J 2C5

  • Women's College Hospital

    Toronto, Ontario, M5S 1B2

  • Sinai Health System

    Toronto, Ontario, M5T 3L9

  • Centre for Addiction and Mental Health (CAMH)

    Toronto, Ontario, M6J 1H4

  • Manna Research

    Toronto, Ontario, M9W 4L6

Other trials in Canada

About this study

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 Outpatients Suffering From a Major Depressive Disorder (MDD) and Having Had - Within the Current Episode - an Inadequate Response to at Least One Psychotropic Medication Included in GeneSight Psychotropic

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.

Read the detailed description

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 outpatients suffering from a MDD and having had - within the current episode - an inadequate response to at least one psychotropic medication included in GEN; 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 a MDD and having had - within the current episode - an inadequate response to at least one psychotropic medication included in GEN. Participants will be randomized in a 1:1:1 ratio to each of the three treatment arms. Recruitment will be 24 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 effect size estimates drawn from a previous study conducted by Hall-Flavin et al [Pharmacogenetics Genomics 2013; 23(10)]. Assuming an effect size of 0.30 in HAM-D17 score favoring the treatment group, intra class coefficient between clusters of 20%, statistical power of 90%, an alpha level of 0.05, and an expected 16.7% rate of premature discontinuation by Week 8 (primary endpoint), a total of 570 subjects (i.e., 190 per treatment arm) are required to detect the same effect in this study.

Being tested
GeneSight Psychotropic (GEN), Enhanced-GeneSight Psychotropic (E-GEN), Treatment as Usual (TAU)
Keywords
Pharmacogenomic, Pharmacogenomic Testing, Pharmacogenomics, Genetic Testing, Genetics, Major Depressive Disorder, GeneSight, Enhanced GeneSight, Psychotropic
Medical subject headings
Depressive Disorder, Major, Depression, Depressive Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

  • 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.

  • 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.

Study groups in NCT02466477
Study groupRoleWhat they receive
GeneSight Psychotropic (GEN)ExperimentalThe 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.
Receives: Genetic: GeneSight Psychotropic (GEN)
Enhanced-GeneSight Psychotropic (E-GEN)ExperimentalThe 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.
Receives: Genetic: Enhanced-GeneSight Psychotropic (E-GEN)
Treatment as Usual (TAU)Active comparatorThe 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.
Receives: Other: Treatment as Usual (TAU)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: From baseline to Week 8

Secondary outcomes (20)
  1. Change in depressive symptoms as assessed by the 16-Item Clinician Quick Inventory of Depressive Symptomatology (QIDS-SR16)

    Measured: Baseline, Weeks 8 and 12, and Month 12

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

    Measured: Baseline, Weeks 8 and 12, and Month 12

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

    Measured: Baseline, Weeks 8 and 12, and Month 12

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

    Measured: Baseline, Week 12 and Month 12

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

    Measured: Week 12, and Month 12

  6. Change in global therapeutic benefit and global severity of side effects as assessed by the Clinical Global Impression Efficacy Index

    Measured: Week 12 and Month 12

  7. Changes to initial prescribing based on availability of pharmacogenomic data

    Measured: Screening and Baseline

  8. Response rates to psychotropic medication

    A responder is defined as a participant with 50% decrease in HAM-D17 score from baseline.

    Measured: Baseline, Weeks 8 and 12, Months 6, 9 and 12

  9. Remission rates

    A remitter is defined as a participant with HAM-D17 score equal or less that 7.

    Measured: Baseline, Weeks 8 and 12, Months 6, 9 and 12

  10. Time to response

    Measured: Baseline, Weeks 8 and 12, Months 6, 9 and 12

  11. Time to remission

    Measured: Baseline, Weeks 8 and 12, Months 6, 9 and 12

  12. Change in psychotropic medication side effects as assessed by the Udvalg for Kliniske Undersogeler (UKU) Side Effect Rating Scale

    Measured: Baseline, Weeks 8 and 12, and Month 12

  13. Change in global measure of side effects (frequency, intensity, and burden domains) as assessed by the Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER)

    Measured: Baseline, Weeks 8 and 12, and Month 12

  14. Weight gain

    Subject's weight

    Measured: Baseline, Weeks 8 and 12, and Month 12

  15. Waist-to-hip ratio

    Subject's waist and hip measurements

    Measured: Baseline, Weeks 8 and 12, and Month 12

  16. Change in health related quality of life as assessed by the EuroQol (EQ-5D-5L)

    Measured: Baseline, Week 12, Months 6, 9 and 12

  17. Change in health related quality of life as assessed by the Short Form (36) Health Survey (SF-36)

    Measured: Baseline, Week 12, Months 6, 9 and 12

  18. Pharmacogenetics in Psychiatry Follow-up Questionnaire (PIPFQ)

    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.

    Measured: Baseline, when prescription changes are made (expected average of every 4 weeks), and Month 12

  19. Healthcare resource utilization (Composite measure of healthcare costs): physician visits, hospital utilization, emergency department visits, medication use, and laboratory tests

    Measured: Baseline, Weeks 8 and 12, Months 6, 9 and 12

  20. Productivity losses (measured as economic costs)

    Measured: Baseline, Weeks 8 and 12, Months 6, 9 and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jun 2015 (estimated)
  2. Study startJun 2015
  3. Primary completionNov 2018
  4. Study completionSep 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
542 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02466477
Sponsor's protocol ID
EXCITE-013304-ARX1009.PTL
Status last verified
Apr 2020
First submitted
3 Jun 2015
Last updated
30 Apr 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 35288545

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing GeneSight Psychotropic (GEN), Enhanced-GeneSight Psychotropic (E-GEN) and Treatment as Usual (TAU) in people with Depressive Disorder, Major and Depression, run by Assurex Health Inc. at 14 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in depressive symptoms as assessed by the 17-item Hamilton Depression (HAM-D17) score (time frame: From baseline to Week 8). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02466477, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2020.

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