Individualizing Antidepressant Treatment Using Pharmacogenomics and EHR-driven Clinical Decision Support (MyGenes)

• ClinicalTrials.gov Identifier: NCT03952494
• Recruitment Status: Withdrawn
• First Posted: May 16, 2019
• Last Update Posted: November 8, 2021
• Sponsor: Weill Medical College of Cornell University
• Collaborator: Leon Lowenstein Foundation Inc.
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Study Description

Brief Summary:

The purpose of this study is to understand the effectiveness of pharmacogenomic testing in using antidepressants and to understand how EHR - driven clinical decision support system can be used to deliver PGx test results by healhcare providers.

Condition or disease	Intervention/treatment	Phase
Depression	Genetic: Genomind®Professional PGx Express TM	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: The myGenes Study:Individualizing Antidepressant Treatment Using Pharmacogenomics and EHR-driven Clinical Decision Support
• Estimated Study Start Date: March 1, 2022
• Estimated Primary Completion Date: February 28, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention group; Intervention group will have the PGx test results available via Epic, three days after the biospecimen is received.	Genetic: Genomind®Professional PGx Express TM; The current test includes the analysis of fifteen pharmacodynamic genes and nine pharmacokinetic genes that have been shown in numerous clinical studies to have implications for response to treatments used for depression, anxiety, obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, Posttraumatic Stress Disorder (PTSD), autism, schizophrenia, chronic pain and substance abuse. The genes assessed by the assay target major hepatic enzymes and key neurotransmitter pathways including serotonin, dopamine, norepinephrine and glutamate.
Experimental: Control group; The control group will be considered in TAU(treatment as usual) group but will have the PGx test results available after 24 weeks. Note: Patient in both the groups will be followed for 24 weeks and will take questionnaires every other week.	Genetic: Genomind®Professional PGx Express TM; The current test includes the analysis of fifteen pharmacodynamic genes and nine pharmacokinetic genes that have been shown in numerous clinical studies to have implications for response to treatments used for depression, anxiety, obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, Posttraumatic Stress Disorder (PTSD), autism, schizophrenia, chronic pain and substance abuse. The genes assessed by the assay target major hepatic enzymes and key neurotransmitter pathways including serotonin, dopamine, norepinephrine and glutamate.

Outcome Measures

Primary Outcome Measures :

1. Response, as defined by > 50% reduction in Hamilton Depressing Rating Scale ( HAM-D) [ Time Frame: 24 weeks ]
   The Hamilton Depression Rating Scale is used for rating the severity of depressive symptoms. Scores range from 0 to 50, with higher scores indicating greater severity of depression. The scoring system is as follows- 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-23 = Severe Depression > 23 = Very severe Depression.
2. Remission, as defined by < 8 on Hamilton Depressing Rating Scale ( HAM-D). [ Time Frame: 24 weeks ]
   The Hamilton Depression Rating Scale is used for rating the severity of depressive symptoms. Scores range from 0 to 50, with higher scores indicating greater severity of depression. The scoring system is as follows- 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-23 = Severe Depression > 23 = Very severe Depression.
3. Conformance between antidepressant medication prescription changes and recommendations from the pharmacogenomics testing [ Time Frame: 24 weeks ]
   Conformance is defined as the number of prescriptions that are in agreement with clinical decision support recommendations based on pharmacogenomics test results.

Secondary Outcome Measures :

1. Self-reported side effects [ Time Frame: 24 weeks ]
   FIBSER (Frequency, intensity and burden of side effects rating) questionnaire will be administered to assess the frequency, severity and degree of impairment related to side effects including nausea, headache, vomiting, GI distress, and sexual dysfunction. Frequency of side-effects are rated from 0-6, with 0 signifying no side effects and score of 6 showing that the effects are present all the time. Similarly intensity is also rated from 0-6 with 0 demonstrating no side effects and 6 signifying that the intensity is intolerable. Interference of side effects in day to day function is also rated in the same way. A reading of 0 tells us that there is no impairment of day-to-day functions and a reading of 6 depicts inability to function.
2. Provider Attitude [ Time Frame: 24 weeks ]
   Number of overwritten CDS alerts regarding PGx testing will be used to determine if PGx-related CDS alerts will result in higher provider uptake compared to non-PGx-related CDS.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 89 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Patients who quality the criteria below:

• Patients with nonpsychotic MDD
• Patients who would like to either start a new antidepressant or change their existing antidepressant treatment
• Patients for whom antidepressant treatment is deemed appropriate by the treating clinician
• >18 years of age
• Willingness to provide signed informed consent to participate in the study
• Will be following up or continuously visiting their physician

Providers:

• Outpatient practice providers
• Providers who are familiar with Epic

Exclusion Criteria:

Patients:

• Patients with medical contraindications that preclude antidepressant treatment
• Patients with schizophrenia, schizoaffective disorder, or who have Bipolar I disorder
• Patients currently on antipsychotic medications (e.g., typical and atypical antipsychotic drugs) and mood stabilizing agents (e.g., lithium, carbamazepine, valproate, lamotrigine, gabapentin, or other anticonvulsants)
• Patients who are pregnant or have severe cognitive impairment
• Patients requiring urgent care or inpatient hospitalization at the time of consent

Providers:

• Unable or unwilling to commit time to introduce myGenes study to patients

Contacts and Locations

Locations

United States, New York

Weill Cornell Medicine

New York, New York, United States, 10065

Sponsors and Collaborators

Weill Medical College of Cornell University

Leon Lowenstein Foundation Inc.

Investigators

• Principal Investigator: Jyotishman Pathak, PhD; Weill Medical College of Cornell University

More Information

Additional Information:

Murray CJ, Lopez AD, Organization WH. The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020: summary. 1996. 

Najafzadeh, Mehdi, Jorge A. Garces, and Alejandra Maciel. 2017. &quot;Economic Evaluation of Implementing a Novel Pharmacogenomic Test (IDgenetix&#174;) to Guide Treatment of Patients with Depression and/or Anxiety.&quot; 

Publications:

Al-Harbi KS. Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Prefer Adherence. 2012;6:369-88. doi: 10.2147/PPA.S29716. Epub 2012 May 1.

Murray CJ, Atkinson C, Bhalla K, Birbeck G, Burstein R, Chou D, Dellavalle R, Danaei G, Ezzati M, Fahimi A, Flaxman D, Foreman, Gabriel S, Gakidou E, Kassebaum N, Khatibzadeh S, Lim S, Lipshultz SE, London S, Lopez, MacIntyre MF, Mokdad AH, Moran A, Moran AE, Mozaffarian D, Murphy T, Naghavi M, Pope C, Roberts T, Salomon J, Schwebel DC, Shahraz S, Sleet DA, Murray, Abraham J, Ali MK, Atkinson C, Bartels DH, Bhalla K, Birbeck G, Burstein R, Chen H, Criqui MH, Dahodwala, Jarlais, Ding EL, Dorsey ER, Ebel BE, Ezzati M, Fahami, Flaxman S, Flaxman AD, Gonzalez-Medina D, Grant B, Hagan H, Hoffman H, Kassebaum N, Khatibzadeh S, Leasher JL, Lin J, Lipshultz SE, Lozano R, Lu Y, Mallinger L, McDermott MM, Micha R, Miller TR, Mokdad AA, Mokdad AH, Mozaffarian D, Naghavi M, Narayan KM, Omer SB, Pelizzari PM, Phillips D, Ranganathan D, Rivara FP, Roberts T, Sampson U, Sanman E, Sapkota A, Schwebel DC, Sharaz S, Shivakoti R, Singh GM, Singh D, Tavakkoli M, Towbin JA, Wilkinson JD, Zabetian A, Murray, Abraham J, Ali MK, Alvardo M, Atkinson C, Baddour LM, Benjamin EJ, Bhalla K, Birbeck G, Bolliger I, Burstein R, Carnahan E, Chou D, Chugh SS, Cohen A, Colson KE, Cooper LT, Couser W, Criqui MH, Dabhadkar KC, Dellavalle RP, Jarlais, Dicker D, Dorsey ER, Duber H, Ebel BE, Engell RE, Ezzati M, Felson DT, Finucane MM, Flaxman S, Flaxman AD, Fleming T, Foreman, Forouzanfar MH, Freedman G, Freeman MK, Gakidou E, Gillum RF, Gonzalez-Medina D, Gosselin R, Gutierrez HR, Hagan H, Havmoeller R, Hoffman H, Jacobsen KH, James SL, Jasrasaria R, Jayarman S, Johns N, Kassebaum N, Khatibzadeh S, Lan Q, Leasher JL, Lim S, Lipshultz SE, London S, Lopez, Lozano R, Lu Y, Mallinger L, Meltzer M, Mensah GA, Michaud C, Miller TR, Mock C, Moffitt TE, Mokdad AA, Mokdad AH, Moran A, Naghavi M, Narayan KM, Nelson RG, Olives C, Omer SB, Ortblad K, Ostro B, Pelizzari PM, Phillips D, Raju M, Razavi H, Ritz B, Roberts T, Sacco RL, Salomon J, Sampson U, Schwebel DC, Shahraz S, Shibuya K, Silberberg D, Singh JA, Steenland K, Taylor JA, Thurston GD, Vavilala MS, Vos T, Wagner GR, Weinstock MA, Weisskopf MG, Wulf S, Murray; U.S. Burden of Disease Collaborators. The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA. 2013 Aug 14;310(6):591-608. doi: 10.1001/jama.2013.13805.

Pérez V, Salavert A, Espadaler J, Tuson M, Saiz-Ruiz J, Sáez-Navarro C, Bobes J, Baca-García E, Vieta E, Olivares JM, Rodriguez-Jimenez R, Villagrán JM, Gascón J, Cañete-Crespillo J, Solé M, Saiz PA, Ibáñez Á, de Diego-Adeliño J; AB-GEN Collaborative Group, Menchón JM. Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial. BMC Psychiatry. 2017 Jul 14;17(1):250. doi: 10.1186/s12888-017-1412-1.

Han C, Wang SM, Bahk WM, Lee SJ, Patkar AA, Masand PS, Mandelli L, Pae CU, Serretti A. A Pharmacogenomic-based Antidepressant Treatment for Patients with Major Depressive Disorder: Results from an 8-week, Randomized, Single-blinded Clinical Trial. Clin Psychopharmacol Neurosci. 2018 Nov 30;16(4):469-480. doi: 10.9758/cpn.2018.16.4.469. Erratum in: Clin Psychopharmacol Neurosci. 2020 Nov 30;18(4):641.

Altar CA, Carhart J, Allen JD, Hall-Flavin D, Winner J, Dechairo B. Clinical Utility of Combinatorial Pharmacogenomics-Guided Antidepressant Therapy: Evidence from Three Clinical Studies. Mol Neuropsychiatry. 2015 Oct;1(3):145-55. doi: 10.1159/000430915. Epub 2015 Jul 31.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT03952494
• Other Study ID Numbers: 1806019379
• First Posted: May 16, 2019
• Last Update Posted: November 8, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Depression; Behavioral Symptoms