PRIME Care (PRecision Medicine In MEntal Health Care)

NCT03170362 | Completed Results

• 1 other identifier: SDR 16-348
• Study Type: interventional
• Target: 1,944
• Locations: 1 country
• Sites: 24

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.

Conditions

Major Depression

Keywords

Treatment; Pharmacogenetics; Depression

Outcome Measures

Primary Outcomes (2)

• Depression Remission

  The investigators will use the Patient Health Questionnaire 9 (PHQ9) as a self assessed marker of depression remission. The scale ranges from 0 to 27 with lower scores indicating less depression severity. Remission was defined as a score of 5 or less at the endpoint. the reported number of participants are those reaching that threshold of symptoms.

  24 weeks post randomization

• Use of Fewer Medications That Have Potential Gene-drug Interactions

  The investigators will examine the proportion of antidepressants prescribed in the first 30 days of the trial that have the potential for gene-drug interactions. The chance for a gene-drug interaction was classified as 1. the subject did not have a prescription for an antidepressant during the initial 4 weeks of the trial (No Antidepressant), 2 the subject was prescribed an antidepressant with no known gene-drug interaction (No Gene Interaction), 3 the subject was prescribed an antidepressant with moderate gene-drug interactions (Moderate Interaction). These are also gene-drug interactions that do not have level A concordance. And 4. the subject was prescribed an antidepressant with substantial gene-drug interactions or gene-drug interactions that are considered to have a high level of evidence to support other prescribing.

  Over the first 30 days

Secondary Outcomes (2)

• Depression Severity

  24 Weeks

• Depression Response

  24 weeks

Study Arms (2)

Intervention group

EXPERIMENTAL

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

Other: Pharmacogenetic Test

Delay results group

NO INTERVENTION

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).

Interventions

Pharmacogenetic Test OTHER

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

Intervention group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• willingness to provide signed, informed consent to participate in the study

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (24)

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

North Little Rock, Arkansas, 72114-1706, United States

Location

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, 94304-1290, United States

Location

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, 94121, United States

Location

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

West Los Angeles, California, 90073, United States

Location

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, 80045, United States

Location

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

West Haven, Connecticut, 06516, United States

Location

Wilmington VA Medical Center, Wilmington, DE

Wilmington, Delaware, 19805, United States

Location

Miami VA Healthcare System, Miami, FL

Miami, Florida, 33125, United States

Location

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

Baltimore, Maryland, 21201, United States

Location

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

Boston, Massachusetts, 02130, United States

Location

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, 48105, United States

Location

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, 55417, United States

Location

New Mexico VA Health Care System, Albuquerque, NM

Albuquerque, New Mexico, 87108-5153, United States

Location

VA Western New York Healthcare System, Buffalo, NY

Buffalo, New York, 14215, United States

Location

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

Salisbury, North Carolina, 28144, United States

Location

Cincinnati VA Medical Center, Cincinnati, OH

Cincinnati, Ohio, 45220, United States

Location

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106, United States

Location

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

Philadelphia, Pennsylvania, 19104, United States

Location

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Pittsburgh, Pennsylvania, 15240, United States

Location

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, 29401-5799, United States

Location

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030, United States

Location

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

Salt Lake City, Utah, 84148, United States

Location

Hunter Holmes McGuire VA Medical Center, Richmond, VA

Richmond, Virginia, 23249, United States

Location

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

Seattle, Washington, 98108, United States

Location

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• Hidalgo-Mazzei D, Berk M, Cipriani A, Cleare AJ, Florio AD, Dietch D, Geddes JR, Goodwin GM, Grunze H, Hayes JF, Jones I, Kasper S, Macritchie K, McAllister-Williams RH, Morriss R, Nayrouz S, Pappa S, Soares JC, Smith DJ, Suppes T, Talbot P, Vieta E, Watson S, Yatham LN, Young AH, Stokes PRA. Treatment-resistant and multi-therapy-resistant criteria for bipolar depression: consensus definition. Br J Psychiatry. 2019 Jan;214(1):27-35. doi: 10.1192/bjp.2018.257. Epub 2018 Dec 6.

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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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• Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Bond DJ, Frey BN, Sharma V, Goldstein BI, Rej S, Beaulieu S, Alda M, MacQueen G, Milev RV, Ravindran A, O'Donovan C, McIntosh D, Lam RW, Vazquez G, Kapczinski F, McIntyre RS, Kozicky J, Kanba S, Lafer B, Suppes T, Calabrese JR, Vieta E, Malhi G, Post RM, Berk M. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018 Mar;20(2):97-170. doi: 10.1111/bdi.12609. Epub 2018 Mar 14.

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• Vieta E, Berk M, Schulze TG, Carvalho AF, Suppes T, Calabrese JR, Gao K, Miskowiak KW, Grande I. Bipolar disorders. Nat Rev Dis Primers. 2018 Mar 8;4:18008. doi: 10.1038/nrdp.2018.8.

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• Gonzalez R, Suppes T, Zeitzer J, McClung C, Tamminga C, Tohen M, Forero A, Dwivedi A, Alvarado A. The association between mood state and chronobiological characteristics in bipolar I disorder: a naturalistic, variable cluster analysis-based study. Int J Bipolar Disord. 2018 Feb 19;6(1):5. doi: 10.1186/s40345-017-0113-5.

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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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• Williams LM, Pines A, Goldstein-Piekarski AN, Rosas LG, Kullar M, Sacchet MD, Gevaert O, Bailenson J, Lavori PW, Dagum P, Wandell B, Correa C, Greenleaf W, Suppes T, Perry LM, Smyth JM, Lewis MA, Venditti EM, Snowden M, Simmons JM, Ma J. The ENGAGE study: Integrating neuroimaging, virtual reality and smartphone sensing to understand self-regulation for managing depression and obesity in a precision medicine model. Behav Res Ther. 2018 Feb;101:58-70. doi: 10.1016/j.brat.2017.09.012. Epub 2017 Oct 7.

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• Lippard ETC, Jensen KP, Wang F, Johnston JAY, Spencer L, Pittman B, Gelernter J, Blumberg HP. Genetic variation of ANK3 is associated with lower white matter structural integrity in bipolar disorder. Mol Psychiatry. 2017 Sep;22(9):1225. doi: 10.1038/mp.2017.169. No abstract available.

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• Stein MB, Chen CY, Jain S, Jensen KP, He F, Heeringa SG, Kessler RC, Maihofer A, Nock MK, Ripke S, Sun X, Thomas ML, Ursano RJ, Smoller JW, Gelernter J; Army STARRS Collaborators. Genetic risk variants for social anxiety. Am J Med Genet B Neuropsychiatr Genet. 2017 Jun;174(4):470-482. doi: 10.1002/ajmg.b.32541. Epub 2017 Apr 27. No abstract available.

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• Stein MB, Chen CY, Jain S, Jensen KP, He F, Heeringa SG, Kessler RC, Maihofer A, Nock MK, Ripke S, Sun X, Thomas ML, Ursano RJ, Smoller JW, Gelernter J; Army STARRS Collaborators. Genetic risk variants for social anxiety. Am J Med Genet B Neuropsychiatr Genet. 2017 Mar;174(2):120-131. doi: 10.1002/ajmg.b.32520.

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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.

  PMID: 35819423 RESULT

• 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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• Montalvo-Ortiz JL, Gelernter J, Cheng Z, Girgenti MJ, Xu K, Zhang X, Gopalan S, Zhou H, Duman RS, Southwick SM, Krystal JH; Traumatic Stress Brain Research Study Group; Pietrzak RH. Epigenome-wide association study of posttraumatic stress disorder identifies novel loci in U.S. military veterans. Transl Psychiatry. 2022 Feb 17;12(1):65. doi: 10.1038/s41398-022-01822-3.

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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.

  PMID: 35802930 RESULT

• 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.

  PMID: 38753374 DERIVED

• 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.

  PMID: 35319502 DERIVED

• 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.

  PMID: 34979178 DERIVED

Related Links

• Website location for educational materials

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Results Point of Contact

• Title: David Oslin
• Organization: Department of Veteran Affairs

dave.oslin@va.gov

215-823-5894

Study Officials

• David W. Oslin, MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: The study intervention is the provision of pharmacogenetic test results which can then be used to choice appropriate medication.

Study Record Dates

• First Submitted: May 26, 2017
• First Posted: May 31, 2017
• Study Start: June 15, 2017
• Primary Completion: October 30, 2021
• Study Completion: March 31, 2022
• Last Updated: May 28, 2024
• Results First Posted: May 28, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 7/1/2022
• Access Criteria: published with article

Locations

US (24)