PRIME Care (PRecision Medicine In MEntal Health Care)

NCT ID: NCT03170362

Last Updated: 2024-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1944 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-15
• Study Completion Date: 2022-03-31

Brief Summary

The focus of this application is on the impact of providing depressed Veterans and their providers with the results of pharmacogenetic (PGx) testing for psychotropic medications. The project focuses on whether and how patients and providers use genetic test results given to them at the time an antidepressant is to be initiated to treat Major Depressive Disorder (MDD) and whether use of the test results improves patient outcomes. MDD is one of the most common conditions associated with military service and combat exposure, increases suicide risk, and worsens the course of common medical conditions, making it a leading cause of functional impairment and mortality. Validation of a PGx test to personalize the treatment of MDD represents an important opportunity to improve the healthcare of Veterans.

Detailed Description

Background: In the last several years, commercial pharmacogenetic (PGx) testing for psychotropic medications has become widespread as a means of implementing "precision medicine", with some insurers electing to cover the cost of testing. These developments have put increasing pressure on the Veterans Health Administration to implement a mental health focused PGxs program, especially for treating depression, but without sufficient scientific study to support the utility of clinical application.

Objectives: The investigators propose a program of research to evaluate the utility of PGx testing in treating Major Depressive Disorder.

Methods: The investigators plan a multi-site RCT (n=2000), patient/provider dyads will be randomly assigned to receive results of the PGx battery right after randomization (i.e. intervention group) or after 6 months of treatment as usual (i.e. delayed results group)The study will test the following hypotheses:

1. Veterans with MDD whose care is guided by the results of the PGx battery (the intervention group) will have a higher rate of remission of depression than the delayed results group. (Primary Hypothesis)

2. Provider/patient dyads in the intervention group will use fewer medications that have potential gene-drug interactions based on commercial PGx test results than dyads in the delayed results group (Primary Hypothesis).

Conditions

Major Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Intervention group

Pharmacogenetic test results will be provided to the provider within 72 hours of randomization in order to facilitate choice in selecting antidepressants.

Group Type: EXPERIMENTAL

Pharmacogenetic Test

Intervention Type: OTHER

The intervention is a battery of pharmacogenetic test results that mostly affect the metabolism of antidepressants and other medications.

Delay results group

The comparator arm will not receive results at the time of randomization but will get results after the 24 week assessment (thus the results are delayed).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Pharmacogenetic Test

The intervention is a battery of pharmacogenetic test results that mostly affect the metabolism of antidepressants and other medications.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• PHQ-9 score 10 and a presumptive diagnosis of MDD per PHQ-9 criteria
• at least one prior treatment exposure for MDD (psychotherapy or antidepressant
• intent to start treatment of the MDD with an antidepressant, simple dose increases will not be considered inclusionary
• willingness to provide signed, informed consent to participate in the study

Exclusion Criteria

• current serious co-occurring psychiatric illness, i.e.:

• schizophrenia
• bipolar disorder
• psychotic major depression
• borderline or antisocial personality disorder
• eating disorder
• active alcohol or other drug use disorder
• current use of an antipsychotic medication
• augmentation therapy, e.g.:

• use of two or more antidepressants at the time of randomization (trazodone at a dosage < 150 mg/day will not be considered augmentation and thus allowed)
• patients requiring urgent care or inpatient hospitalization at the time of consent
• currently incarcerated

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David W. Oslin, MD

Role: PRINCIPAL_INVESTIGATOR

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Locations

Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR

North Little Rock, Arkansas, United States

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, United States

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, United States

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, United States

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, United States

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

West Haven, Connecticut, United States

Wilmington VA Medical Center, Wilmington, DE

Wilmington, Delaware, United States

Miami VA Healthcare System, Miami, FL

Miami, Florida, United States

Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

Baltimore, Maryland, United States

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, United States

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, United States

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, United States

New Mexico VA Health Care System, Albuquerque, NM

Albuquerque, New Mexico, United States

VA Western New York Healthcare System, Buffalo, NY

Buffalo, New York, United States

Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC

Salisbury, North Carolina, United States

Cincinnati VA Medical Center, Cincinnati, OH

Cincinnati, Ohio, United States

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, United States

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Philadelphia, Pennsylvania, United States

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Pittsburgh, Pennsylvania, United States

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, United States

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States

VA Salt Lake City Health Care System, Salt Lake City, UT

Salt Lake City, Utah, United States

Hunter Holmes McGuire VA Medical Center, Richmond, VA

Richmond, Virginia, United States

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, United States

Countries

United States

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Ward RE, Cho K, Nguyen XT, Vassy JL, Ho YL, Quaden RM, Gagnon DR, Wilson PWF, Gaziano JM, Djousse L; VA Million Veteran Program. Omega-3 supplement use, fish intake, and risk of non-fatal coronary artery disease and ischemic stroke in the Million Veteran Program. Clin Nutr. 2020 Feb;39(2):574-579. doi: 10.1016/j.clnu.2019.03.005. Epub 2019 Mar 13.

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Raghavan S, Vassy JL, Ho YL, Song RJ, Gagnon DR, Cho K, Wilson PWF, Phillips LS. Diabetes Mellitus-Related All-Cause and Cardiovascular Mortality in a National Cohort of Adults. J Am Heart Assoc. 2019 Feb 19;8(4):e011295. doi: 10.1161/JAHA.118.011295.

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van der Markt A, Klumpers UM, Draisma S, Dols A, Nolen WA, Post RM, Altshuler LL, Frye MA, Grunze H, Keck PE Jr, McElroy SL, Suppes T, Beekman AT, Kupka RW. Testing a clinical staging model for bipolar disorder using longitudinal life chart data. Bipolar Disord. 2019 May;21(3):228-234. doi: 10.1111/bdi.12727. Epub 2018 Dec 12.

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Imran TF, Posner D, Honerlaw J, Vassy JL, Song RJ, Ho YL, Kittner SJ, Liao KP, Cai T, O'Donnell CJ, Djousse L, Gagnon DR, Gaziano JM, Wilson PW, Cho K. A phenotyping algorithm to identify acute ischemic stroke accurately from a national biobank: the Million Veteran Program. Clin Epidemiol. 2018 Oct 16;10:1509-1521. doi: 10.2147/CLEP.S160764. eCollection 2018.

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Post RM, Altshuler LL, Kupka R, McElroy SL, Frye MA, Rowe M, Grunze H, Suppes T, Keck PE Jr, Leverich GS, Nolen WA. Multigenerational transmission of liability to psychiatric illness in offspring of parents with bipolar disorder. Bipolar Disord. 2018 Jun 21. doi: 10.1111/bdi.12668. Online ahead of print.

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Post RM, Leverich GS, McElroy S, Kupka R, Suppes T, Altshuler L, Nolen W, Frye M, Keck P, Grunze H, Hellemann G. Prevalence of axis II comorbidities in bipolar disorder: relationship to mood state. Bipolar Disord. 2018 Jun;20(4):303-312. doi: 10.1111/bdi.12596. Epub 2018 Jan 25.

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Hull LE, Lynch KG, Oslin DW. VA Primary Care and Mental Health Providers' Comfort with Genetic Testing: Survey Results from the PRIME Care Study. J Gen Intern Med. 2019 Jun;34(6):799-801. doi: 10.1007/s11606-018-4776-0. No abstract available.

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Chanfreau-Coffinier C, Hull LE, Lynch JA, DuVall SL, Damrauer SM, Cunningham FE, Voight BF, Matheny ME, Oslin DW, Icardi MS, Tuteja S. Projected Prevalence of Actionable Pharmacogenetic Variants and Level A Drugs Prescribed Among US Veterans Health Administration Pharmacy Users. JAMA Netw Open. 2019 Jun 5;2(6):e195345. doi: 10.1001/jamanetworkopen.2019.5345.

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Hull LE, Chanfreau-Coffinier C, Tuteja S, Berlowitz D, Lehmann LS, Oslin DW, Pyne JM, DuVall SL, Lynch JA. Early adoption of pharmacogenetic testing for veterans prescribed psychotropic medications. Pharmacogenomics. 2019 Jul;20(11):781-789. doi: 10.2217/pgs-2019-0065. Epub 2019 Aug 8.

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Oslin DW, Chapman S, Duvall SL, Gelernter J, Ingram EP, Kranzler HR, Lehmann LS, Lynch JA, Lynch KG, Pyne JM, Shih MC, Stone A, Thase ME, Wray LO. Study design and implementation of the PRecision Medicine In MEntal health Care (PRIME Care) Trial. Contemp Clin Trials. 2021 Feb;101:106247. doi: 10.1016/j.cct.2020.106247. Epub 2020 Dec 11.

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Vest BM, Wray LO, Brady LA, Thase ME, Beehler GP, Chapman SR, Hull LE, Oslin DW. Primary care and mental health providers' perceptions of implementation of pharmacogenetics testing for depression prescribing. BMC Psychiatry. 2020 Oct 28;20(1):518. doi: 10.1186/s12888-020-02919-z.

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Ramsey CM, Lynch KG, Thase ME, Gelernter J, Kranzler HR, Pyne JM, Shih MC, Stone A; PRIME Care Executive Committee; Oslin DW. Prevalence of predicted gene-drug interactions for antidepressants in the treatment of major depressive disorder in the Precision Medicine in Mental Health Care Study. J Affect Disord. 2021 Mar 1;282:1272-1277. doi: 10.1016/j.jad.2021.01.034. Epub 2021 Jan 14.

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Oslin DW, Lynch KG, Shih MC, Ingram EP, Wray LO, Chapman SR, Kranzler HR, Gelernter J, Pyne JM, Stone A, DuVall SL, Lehmann LS, Thase ME; PRIME Care Research Group; Aslam M, Batki SL, Bjork JM, Blow FC, Brenner LA, Chen P, Desai S, Dieperink EW, Fears SC, Fuller MA, Goodman CS, Graham DP, Haas GL, Hamner MB, Helstrom AW, Hurley RA, Icardi MS, Jurjus GJ, Kilbourne AM, Kreyenbuhl J, Lache DJ, Lieske SP, Lynch JA, Meyer LJ, Montalvo C, Muralidhar S, Ostacher MJ, Paschall GY, Pfeiffer PN, Prieto S, Przygodzki RM, Ranganathan M, Rodriguez-Suarez MM, Roggenkamp H, Schichman SA, Schneeweis JS, Simonetti JA, Steinhauer SR, Suppes T, Umbert MA, Vassy JL, Voora D, Wiechers IR, Wood AE. Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder: The PRIME Care Randomized Clinical Trial. JAMA. 2022 Jul 12;328(2):151-161. doi: 10.1001/jama.2022.9805.

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PMID: 35819423 (View on PubMed)

Ziobrowski HN, Cui R, Ross EL, Liu H, Puac-Polanco V, Turner B, Leung LB, Bossarte RM, Bryant C, Pigeon WR, Oslin DW, Post EP, Zaslavsky AM, Zubizarreta JR, Nierenberg AA, Luedtke A, Kennedy CJ, Kessler RC. Development of a model to predict psychotherapy response for depression among Veterans. Psychol Med. 2023 Jun;53(8):3591-3600. doi: 10.1017/S0033291722000228. Epub 2022 Feb 11.

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Na PJ, De Angelis F, Nichter B, Wendt FR, Krystal JH, Southwick SM, Levey DF, Gelernter J, Polimanti R, Pietrzak RH. Psychosocial moderators of polygenic risk for suicidal ideation: Results from a 7-year population-based, prospective cohort study of U.S. veterans. Mol Psychiatry. 2022 Feb;27(2):1068-1074. doi: 10.1038/s41380-021-01352-2. Epub 2021 Nov 2.

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Tamman AJF, Wendt FR, Pathak GA, Krystal JH, Southwick SM, Sippel LM, Gelernter J, Polimanti R, Pietrzak RH. Attachment Style Moderates Polygenic Risk for Incident Posttraumatic Stress in U.S. Military Veterans: A 7-Year, Nationally Representative, Prospective Cohort Study. Biol Psychiatry. 2022 Apr 1;91(7):637-646. doi: 10.1016/j.biopsych.2021.09.025. Epub 2021 Oct 6.

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Verma A, Huffman JE, Gao L, Minnier J, Wu WC, Cho K, Ho YL, Gorman BR, Pyarajan S, Rajeevan N, Garcon H, Joseph J, McGeary JE, Suzuki A, Reaven PD, Wan ES, Lynch JA, Petersen JM, Meigs JB, Freiberg MS, Gatsby E, Lynch KE, Zekavat SM, Natarajan P, Dalal S, Jhala DN, Arjomandi M, Bonomo RA, Thompson TK, Pathak GA, Zhou JJ, Donskey CJ, Madduri RK, Wells QS, Gelernter J, Huang RDL, Polimanti R, Chang KM, Liao KP, Tsao PS, Sun YV, Wilson PWF, O'Donnell CJ, Hung AM, Gaziano JM, Hauger RL, Iyengar SK, Luoh SW; VA Million Veteran Program COVID-19 Science Initiative. Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait. JAMA Intern Med. 2022 Aug 1;182(8):796-804. doi: 10.1001/jamainternmed.2022.2141.

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Na PJ, Montalvo-Ortiz JL, Nagamatsu ST, Southwick SM, Krystal JH, Gelernter J, Pietrzak RH. Association of Symptoms of Posttraumatic Stress Disorder and GrimAge, an Epigenetic Marker of Mortality Risk, in US Military Veterans. J Clin Psychiatry. 2022 Jul 6;83(4):21br14309. doi: 10.4088/JCP.21br14309. No abstract available.

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PMID: 35802930 (View on PubMed)

Reis DJ, Kinney AR, Forster JE, Stearns-Yoder KA, Kittel JA, Wood AE, Oslin DW, Brenner LA, Simonetti JA. Longitudinal invariance of the Patient Health Questionnaire-9 among patients receiving pharmacotherapy for major depressive disorder: A secondary analysis of clinical trial data. Psychol Assess. 2024 Aug;36(8):462-471. doi: 10.1037/pas0001317. Epub 2024 May 16.

Reference Type: DERIVED

PMID: 38753374 (View on PubMed)

Chanfreau-Coffinier C, Tuteja S, Hull LE, MacDonald S, Efimova O, Bates J, Voora D, Oslin DW, DuVall SL, Lynch JA. Drug-drug-gene interaction risk among opioid users in the U.S. Department of Veterans Affairs. Pain. 2022 Dec 1;163(12):2390-2397. doi: 10.1097/j.pain.0000000000002637. Epub 2022 Mar 23.

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PMID: 35319502 (View on PubMed)

Ramsey CM, Lynch KG, Gehrman PR, Vairavan S, Narayan VA, Li QS, Oslin DW. Daily steps and depressive symptoms: A longitudinal evaluation of patients with major depressive disorder in the precision medicine in mental health care study. J Affect Disord. 2022 Mar 1;300:334-340. doi: 10.1016/j.jad.2021.12.116. Epub 2022 Jan 1.

Reference Type: DERIVED

PMID: 34979178 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

https://www.mirecc.va.gov/visn4/PrimeCare/PRIME_Care.asp

Website location for educational materials

Other Identifiers

SDR 16-348

Identifier Type: -

Identifier Source: org_study_id