PRIME Care (PRecision Medicine In MEntal Health Care)

Major Depression Clinical Trial

— PRIME Care  

Official title:

PRIME Care (PRecision Medicine In MEntal Health Care)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03170362
• Other study ID #: SDR 16-348
• Status: Completed
• Phase: N/A
• Start date: June 15, 2017
• Est. completion date: March 31, 2022

Study information

• Verified date: May 2024
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1944
• Est. completion date: March 31, 2022
• Est. primary completion date: October 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Major Depression

Intervention

Other:
• Pharmacogenetic Test
The intervention is a battery of pharmacogenetic test results that mostly affect the metabolism of antidepressants and other medications.

Locations

Country	Name	City	State
United States	New Mexico VA Health Care System, Albuquerque, NM	Albuquerque	New Mexico
United States	VA Ann Arbor Healthcare System, Ann Arbor, MI	Ann Arbor	Michigan
United States	Rocky Mountain Regional VA Medical Center, Aurora, CO	Aurora	Colorado
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 Western New York Healthcare System, Buffalo, NY	Buffalo	New York
United States	Ralph H. Johnson VA Medical Center, Charleston, SC	Charleston	South Carolina
United States	Cincinnati VA Medical Center, Cincinnati, OH	Cincinnati	Ohio
United States	Louis Stokes VA Medical Center, Cleveland, OH	Cleveland	Ohio
United States	Michael E. DeBakey VA Medical Center, Houston, TX	Houston	Texas
United States	Miami VA Healthcare System, Miami, FL	Miami	Florida
United States	Minneapolis VA Health Care System, Minneapolis, MN	Minneapolis	Minnesota
United States	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	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	Hunter Holmes McGuire VA Medical Center, Richmond, VA	Richmond	Virginia
United States	Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC	Salisbury	North Carolina
United States	VA Salt Lake City Health Care System, Salt Lake City, UT	Salt Lake City	Utah
United States	San Francisco VA Medical Center, San Francisco, CA	San Francisco	California
United States	VA Puget Sound Health Care System Seattle Division, Seattle, WA	Seattle	Washington
United States	VA Connecticut Healthcare System West Haven Campus, West Haven, CT	West Haven	Connecticut
United States	VA Greater Los Angeles Healthcare System, West Los Angeles, CA	West Los Angeles	California
United States	Wilmington VA Medical Center, Wilmington, DE	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

References & Publications (52)

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 Admini — View Citation

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Hartwell EE, Feinn R, Morris PE, Gelernter J, Krystal J, Arias AJ, Hoffman M, Petrakis I, Gueorguieva R, Schacht JP, Oslin D, Anton RF, Kranzler HR. Systematic review and meta-analysis of the moderating effect of rs1799971 in OPRM1, the mu-opioid receptor gene, on response to naltrexone treatment of alcohol use disorder. Addiction. 2020 Aug;115(8):1426-1437. doi: 10.1111/add.14975. Epub 2020 Feb 11. — View Citation

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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. Erratum In: Br J Psychiatry. 2019 May;214(5):309. — View Citation

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/ — View Citation

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. — View Citation

Hunter-Zinck H, Shi Y, Li M, Gorman BR, Ji SG, Sun N, Webster T, Liem A, Hsieh P, Devineni P, Karnam P, Gong X, Radhakrishnan L, Schmidt J, Assimes TL, Huang J, Pan C, Humphries D, Brophy M, Moser J, Muralidhar S, Huang GD, Przygodzki R, Concato J, Gaziano JM, Gelernter J, O'Donnell CJ, Hauser ER, Zhao H, O'Leary TJ; VA Million Veteran Program; Tsao PS, Pyarajan S. Genotyping Array Design and Data Quality Control in the Million Veteran Program. Am J Hum Genet. 2020 Apr 2;106(4):535-548. doi: 10.1016/j.ajhg.2020.03.004. — View Citation

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Levey DF, Gelernter J, Polimanti R, Zhou H, Cheng Z, Aslan M, Quaden R, Concato J, Radhakrishnan K, Bryois J, Sullivan PF; Million Veteran Program; Stein MB. Reproducible Genetic Risk Loci for Anxiety: Results From approximately 200,000 Participants in the Million Veteran Program. Am J Psychiatry. 2020 Mar 1;177(3):223-232. doi: 10.1176/appi.ajp.2019.19030256. Epub 2020 Jan 7. — View Citation

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. — View Citation

Marees AT, Gamazon ER, Gerring Z, Vorspan F, Fingal J, van den Brink W, Smit DJA, Verweij KJH, Kranzler HR, Sherva R, Farrer L; International Cannabis Consortium; Gelernter J, Derks EM. Post-GWAS analysis of six substance use traits improves the identification and functional interpretation of genetic risk loci. Drug Alcohol Depend. 2020 Jan 1;206:107703. doi: 10.1016/j.drugalcdep.2019.107703. Epub 2019 Nov 4. — View Citation

McIntyre RS, Subramaniapillai M, Lee Y, Pan Z, Carmona NE, Shekotikhina M, Rosenblat JD, Brietzke E, Soczynska JK, Cosgrove VE, Miller S, Fischer EG, Kramer NE, Dunlap K, Suppes T, Mansur RB. Efficacy of Adjunctive Infliximab vs Placebo in the Treatment of Adults With Bipolar I/II Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2019 Aug 1;76(8):783-790. doi: 10.1001/jamapsychiatry.2019.0779. — View Citation

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 identif — View Citation

Muniz Carvalho C, Wendt FR, Maihofer AX, Stein DJ, Stein MB, Sumner JA, Hemmings SMJ, Nievergelt CM, Koenen KC, Gelernter J, Belangero SI, Polimanti R. Dissecting the genetic association of C-reactive protein with PTSD, traumatic events, and social support. Neuropsychopharmacology. 2021 May;46(6):1071-1077. doi: 10.1038/s41386-020-0655-6. Epub 2020 Mar 16. — View Citation

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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 — View Citation

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Nievergelt CM, Maihofer AX, Klengel T, Atkinson EG, Chen CY, Choi KW, Coleman JRI, Dalvie S, Duncan LE, Gelernter J, Levey DF, Logue MW, Polimanti R, Provost AC, Ratanatharathorn A, Stein MB, Torres K, Aiello AE, Almli LM, Amstadter AB, Andersen SB, Andreassen OA, Arbisi PA, Ashley-Koch AE, Austin SB, Avdibegovic E, Babic D, Baekvad-Hansen M, Baker DG, Beckham JC, Bierut LJ, Bisson JI, Boks MP, Bolger EA, Borglum AD, Bradley B, Brashear M, Breen G, Bryant RA, Bustamante AC, Bybjerg-Grauholm J, Calabrese JR, Caldas-de-Almeida JM, Dale AM, Daly MJ, Daskalakis NP, Deckert J, Delahanty DL, Dennis MF, Disner SG, Domschke K, Dzubur-Kulenovic A, Erbes CR, Evans A, Farrer LA, Feeny NC, Flory JD, Forbes D, Franz CE, Galea S, Garrett ME, Gelaye B, Geuze E, Gillespie C, Uka AG, Gordon SD, Guffanti G, Hammamieh R, Harnal S, Hauser MA, Heath AC, Hemmings SMJ, Hougaard DM, Jakovljevic M, Jett M, Johnson EO, Jones I, Jovanovic T, Qin XJ, Junglen AG, Karstoft KI, Kaufman ML, Kessler RC, Khan A, Kimbrel NA, King AP, Koen N, Kranzler HR, Kremen WS, Lawford BR, Lebois LAM, Lewis CE, Linnstaedt SD, Lori A, Lugonja B, Luykx JJ, Lyons MJ, Maples-Keller J, Marmar C, Martin AR, Martin NG, Maurer D, Mavissakalian MR, McFarlane A, McGlinchey RE, McLaughlin KA, McLean SA, McLeay S, Mehta D, Milberg WP, Miller MW, Morey RA, Morris CP, Mors O, Mortensen PB, Neale BM, Nelson EC, Nordentoft M, Norman SB, O'Donnell M, Orcutt HK, Panizzon MS, Peters ES, Peterson AL, Peverill M, Pietrzak RH, Polusny MA, Rice JP, Ripke S, Risbrough VB, Roberts AL, Rothbaum AO, Rothbaum BO, Roy-Byrne P, Ruggiero K, Rung A, Rutten BPF, Saccone NL, Sanchez SE, Schijven D, Seedat S, Seligowski AV, Seng JS, Sheerin CM, Silove D, Smith AK, Smoller JW, Sponheim SR, Stein DJ, Stevens JS, Sumner JA, Teicher MH, Thompson WK, Trapido E, Uddin M, Ursano RJ, van den Heuvel LL, Van Hooff M, Vermetten E, Vinkers CH, Voisey J, Wang Y, Wang Z, Werge T, Williams MA, Williamson DE, Winternitz S, Wolf C, Wolf EJ, Wolff JD, Yehuda R, Young RM, Young KA, Zhao H, Zoellner LA, Liberzon I, Ressler KJ, Haas M, Koenen KC. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci. Nat Commun. 2019 Oct 8;10(1):4558. doi: 10.1038/s41467-019-12576-w. — View Citation

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 — View Citation

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Polimanti R, Walters RK, Johnson EC, McClintick JN, Adkins AE, Adkins DE, Bacanu SA, Bierut LJ, Bigdeli TB, Brown S, Bucholz KK, Copeland WE, Costello EJ, Degenhardt L, Farrer LA, Foroud TM, Fox L, Goate AM, Grucza R, Hack LM, Hancock DB, Hartz SM, Heath AC, Hewitt JK, Hopfer CJ, Johnson EO, Kendler KS, Kranzler HR, Krauter K, Lai D, Madden PAF, Martin NG, Maes HH, Nelson EC, Peterson RE, Porjesz B, Riley BP, Saccone N, Stallings M, Wall TL, Webb BT, Wetherill L; Psychiatric Genomics Consortium Substance Use Disorders Workgroup; Edenberg HJ, Agrawal A, Gelernter J. Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium. Mol Psychiatry. 2020 Aug;25(8):1673-1687. doi: 10.1038/s41380-020-0677-9. Epub 2020 Feb 26. — View Citation

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* Note: There are 52 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Depression Severity	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. This measure will use the PHQ9 as a continuous measure. The reported outcome is the difference in scores from baseline to 24 weeks.	24 Weeks
Secondary	Depression Response	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. Response was measured by a 50% reduction in scores from baseline to each time point.	24 weeks

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