Enabling Personalized Medicine Through Exome Sequencing in the U.S. Air Force

NCT03276637 | Completed Results DMC

• 1 other identifier: The MilSeq Project
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 3

Brief Summary

The MilSeq Project is a nonrandomized, prospective pilot study of whole exome sequencing (WES) in the U.S. Air Force. The purpose of this study is to explore the implementation of WES into clinical medical care in the military health system.

Conditions

Healthy Adults; Genetic Predisposition to Disease

Keywords

Whole Genome Sequencing; Whole Exome Sequencing; Military; Air Force; Disease Susceptibility; Genetic Predisposition to Disease; Disease Attributes; Pathologic Processes

Outcome Measures

Primary Outcomes (4)

• Active-duty Airmen's Perceptions About Military Use of Genomic Information to Make Career Decisions

  Assessed using a novel measure of perceptions about use of genetic information for military career duty assignment decisions on a 1-5 scale, where higher scores indicate more positive attitudes.

  Baseline and 6 weeks post disclosure of genomic sequencing results (approx. 43 weeks after baseline)

• Genomic Sequencing Findings

  Analysis of whole exome sequencing results identified the number of participants with genomic findings, including monogenic disease risk, carrier status, and risk allele presence.

  Results disclosure (within 1 month of sequencing completion)

• Active-duty Airmen Reported Health Care Utilization Related to Study Results

  Participants' health care utilization was assessed through a combination of medical record reviews and novel and adapted measures from the Behavioral Risk Factor Surveillance System (BRFSS). Survey self-report data were compared to services and procedures indicated on medical record review.

  6 weeks post-disclosure (approx. 43 weeks after baseline)

• Military Healthcare Providers' Genomic Literacy

  Military healthcare provider-participants' genomic literacy were measured with a 14-item measure adapted from the ClinSeq Study (Kaphingst K.A. et al. 2012) administered at baseline, before (pre) and immediately after (post) an education session, and at Follow-up near the end of the study. Items are marked as correct (1) or incorrect (0) and summed for a total scale range of 0 to 14, with higher scores indicating higher genomic literacy.

  Baseline (pre and post) and Follow-up (follow-up administered approx. 53 weeks after baseline)

Secondary Outcomes (3)

• Active-duty Airmen Attitudes and Perceived Utility Toward Genomic Sequencing

  Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline)

• Active-duty Airmen's Health Perceptions

  Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline)

• Military Healthcare Providers' Confidence With Genomic Data

  Baseline (pre and post) and Follow-up (follow-up administered approx. 53 weeks after baseline)

Study Arms (2)

Healthy Active-Duty Airmen Cohort

EXPERIMENTAL

Whole exome sequencing (WES) will be performed on 75 ostensibly healthy, active-duty Airmen (patient-participants) who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving WES. Military healthcare providers who have received brief genomics training will return results to the patient-participants and the WES reports will be permanently integrated into their electronic medical record.

Genetic: Whole exome sequencing

Healthcare Provider Cohort

NO INTERVENTION

The Healthcare providers who provide medical care in military Primary Care, Internal Medicine and/or Family Practice settings and enroll participants. Military healthcare providers have received a brief genomics training and will return results to the patient-participants

Interventions

Whole exome sequencing GENETIC

Whole exome sequencing at 125x coverage (i.e., at least 125 sequencing reads covering each position within the exome region of interest) performed at the Laboratory of Molecular Medicine's Clinical Laboratory Improvement Amendments (CLIA) certified laboratory on 75 enrolled individuals

Healthy Active-Duty Airmen Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• An active Air Force Airman
• Fluent in English
• Seen or eligible to be seen by a provider at Wilford Hall Ambulatory Surgical Center at Joint Base San Antonio (JBSA) Lackland Air Force Base
• An active or Department of Defense civilian Primary Care, Internal Medicine, or Family Practice Healthcare Provider (Physician, Physician Assistant, or Nurse Practitioner) or resident practicing at Wilford Hall Ambulatory Surgical Center at JBSA Lackland Air Force Base

You may not qualify if:

• Those with clinically concerning scores on anxiety and distress scales in baseline survey
• Trainees (basic military training or tech school)
• Airmen with an active change of duty station order or deployment order and expected to leave San Antonio in 6 months or less
• Airmen expected to be discharged from the Air Force in 6 months or less
• Providers with an active change of duty station order or deployment order and expected to leave San Antonio in 6 months or less
• Providers expected to be discharged from the Air Force in 6 months or less

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• United States Department of Defense: collaborator

Study Sites (3)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Joint Base San Antonio Lackland Air Force Base - 59th Medical Wing

San Antonio, Texas, 78236, United States

Location

Related Publications (23)

• McMorrow D. The $100 genome: implications for the DoD. Technical Report. McLean, Virginia: The MITRE Corporation; 2010.

  BACKGROUND

• De Castro M, Biesecker LG, Turner C, Brenner R, Witkop C, Mehlman M, Bradburne C, Green RC. Genomic medicine in the military. NPJ Genom Med. 2016 Jan 13;1:15008. doi: 10.1038/npjgenmed.2015.8. eCollection 2016.

  PMID: 29263806 BACKGROUND

• Collins FS, Guttmacher AE. Genetics moves into the medical mainstream. JAMA. 2001 Nov 14;286(18):2322-4. doi: 10.1001/jama.286.18.2322. No abstract available.

  PMID: 11710899 BACKGROUND

• Collins FS, Green ED, Guttmacher AE, Guyer MS; US National Human Genome Research Institute. A vision for the future of genomics research. Nature. 2003 Apr 24;422(6934):835-47. doi: 10.1038/nature01626. Epub 2003 Apr 14. No abstract available.

  PMID: 12695777 BACKGROUND

• McCarthy JJ, McLeod HL, Ginsburg GS. Genomic medicine: a decade of successes, challenges, and opportunities. Sci Transl Med. 2013 Jun 12;5(189):189sr4. doi: 10.1126/scitranslmed.3005785.

  PMID: 23761042 BACKGROUND

• Green RC, Rehm HL, Kohane IS. Clinical genome sequencing. In: Ginsburg GS, Willard HF, eds. Genomic and Personalized Medicine. 2nd ed. San Diego: Academic Press; 2013:102-22.

  BACKGROUND

• Christensen KD, Vassy JL, Jamal L, Lehmann LS, Slashinski MJ, Perry DL, Robinson JO, Blumenthal-Barby J, Feuerman LZ, Murray MF, Green RC, McGuire AL; MedSeq Project Team. Are physicians prepared for whole genome sequencing? a qualitative analysis. Clin Genet. 2016 Feb;89(2):228-34. doi: 10.1111/cge.12626. Epub 2015 Jul 7.

  PMID: 26080898 BACKGROUND

• Vassy JL, Christensen KD, Slashinski MJ, Lautenbach DM, Raghavan S, Robinson JO, Blumenthal-Barby J, Feuerman LZ, Lehmann LS, Murray MF, Green RC, McGuire AL. 'Someday it will be the norm': physician perspectives on the utility of genome sequencing for patient care in the MedSeq Project. Per Med. 2015;12(1):23-32. doi: 10.2217/pme.14.68.

  PMID: 25642274 BACKGROUND

• Vassy JL, Lautenbach DM, McLaughlin HM, Kong SW, Christensen KD, Krier J, Kohane IS, Feuerman LZ, Blumenthal-Barby J, Roberts JS, Lehmann LS, Ho CY, Ubel PA, MacRae CA, Seidman CE, Murray MF, McGuire AL, Rehm HL, Green RC; MedSeq Project. The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine. Trials. 2014 Mar 20;15:85. doi: 10.1186/1745-6215-15-85.

  PMID: 24645908 BACKGROUND

• Johnston JJ, Lewis KL, Ng D, Singh LN, Wynter J, Brewer C, Brooks BP, Brownell I, Candotti F, Gonsalves SG, Hart SP, Kong HH, Rother KI, Sokolic R, Solomon BD, Zein WM, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG. Individualized iterative phenotyping for genome-wide analysis of loss-of-function mutations. Am J Hum Genet. 2015 Jun 4;96(6):913-25. doi: 10.1016/j.ajhg.2015.04.013.

  PMID: 26046366 BACKGROUND

• Green RC, Lautenbach D, McGuire AL. GINA, genetic discrimination, and genomic medicine. N Engl J Med. 2015 Jan 29;372(5):397-9. doi: 10.1056/NEJMp1404776. No abstract available.

  PMID: 25629736 BACKGROUND

• Robinson JO, Carroll TM, Feuerman LZ, Perry DL, Hoffman-Andrews L, Walsh RC, Christensen KD, Green RC, McGuire AL; MedSeq Project Team. Participants and Study Decliners' Perspectives About the Risks of Participating in a Clinical Trial of Whole Genome Sequencing. J Empir Res Hum Res Ethics. 2016 Feb;11(1):21-30. doi: 10.1177/1556264615624078. Epub 2016 Feb 28.

  PMID: 26928896 BACKGROUND

• Vassy JL, McLaughlin HM, MacRae CA, Seidman CE, Lautenbach D, Krier JB, Lane WJ, Kohane IS, Murray MF, McGuire AL, Rehm HL, Green RC. A one-page summary report of genome sequencing for the healthy adult. Public Health Genomics. 2015;18(2):123-9. doi: 10.1159/000370102. Epub 2015 Jan 21.

  PMID: 25612602 BACKGROUND

• Krier J, McLaughlin HM, Lane WJ, et al. The return of pharmacogenomic variants in the MedSeq Project: reporting approach and physician response. Annual Meeting of the American Society of Human Genetics. Boston, MA2013

  BACKGROUND

• Lane WJ, Westhoff CM, Uy JM, Aguad M, Smeland-Wagman R, Kaufman RM, Rehm HL, Green RC, Silberstein LE; MedSeq Project. Comprehensive red blood cell and platelet antigen prediction from whole genome sequencing: proof of principle. Transfusion. 2016 Mar;56(3):743-54. doi: 10.1111/trf.13416. Epub 2015 Dec 3.

  PMID: 26634332 BACKGROUND

• Giovanni MA, Krier J, Vassy JL, Lautenbach DM, Green RC, Murray MF. A brief curriculum for physician orientation to clinical whole genome sequencing. American Society of Human Genetics Annual Meeting. Boston, MA2013.

  BACKGROUND

• Krier JB, Blout CB, D L, et al. Communication and management of genomic sequencing results by non-geneticist physicians. American Society of Human Genetics; 2015; Baltimore, MD.

  BACKGROUND

• Green RC, Goddard KAB, Jarvik GP, Amendola LM, Appelbaum PS, Berg JS, Bernhardt BA, Biesecker LG, Biswas S, Blout CL, Bowling KM, Brothers KB, Burke W, Caga-Anan CF, Chinnaiyan AM, Chung WK, Clayton EW, Cooper GM, East K, Evans JP, Fullerton SM, Garraway LA, Garrett JR, Gray SW, Henderson GE, Hindorff LA, Holm IA, Lewis MH, Hutter CM, Janne PA, Joffe S, Kaufman D, Knoppers BM, Koenig BA, Krantz ID, Manolio TA, McCullough L, McEwen J, McGuire A, Muzny D, Myers RM, Nickerson DA, Ou J, Parsons DW, Petersen GM, Plon SE, Rehm HL, Roberts JS, Robinson D, Salama JS, Scollon S, Sharp RR, Shirts B, Spinner NB, Tabor HK, Tarczy-Hornoch P, Veenstra DL, Wagle N, Weck K, Wilfond BS, Wilhelmsen K, Wolf SM, Wynn J, Yu JH; CSER Consortium. Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine. Am J Hum Genet. 2016 Jun 2;98(6):1051-1066. doi: 10.1016/j.ajhg.2016.04.011. Epub 2016 May 12.

  PMID: 27181682 BACKGROUND

• Berg JS, Agrawal PB, Bailey DB Jr, Beggs AH, Brenner SE, Brower AM, Cakici JA, Ceyhan-Birsoy O, Chan K, Chen F, Currier RJ, Dukhovny D, Green RC, Harris-Wai J, Holm IA, Iglesias B, Joseph G, Kingsmore SF, Koenig BA, Kwok PY, Lantos J, Leeder SJ, Lewis MA, McGuire AL, Milko LV, Mooney SD, Parad RB, Pereira S, Petrikin J, Powell BC, Powell CM, Puck JM, Rehm HL, Risch N, Roche M, Shieh JT, Veeraraghavan N, Watson MS, Willig L, Yu TW, Urv T, Wise AL. Newborn Sequencing in Genomic Medicine and Public Health. Pediatrics. 2017 Feb;139(2):e20162252. doi: 10.1542/peds.2016-2252. Epub 2017 Jan 17.

  PMID: 28096516 BACKGROUND

• Kaphingst KA, Facio FM, Cheng MR, Brooks S, Eidem H, Linn A, Biesecker BB, Biesecker LG. Effects of informed consent for individual genome sequencing on relevant knowledge. Clin Genet. 2012 Nov;82(5):408-15. doi: 10.1111/j.1399-0004.2012.01909.x. Epub 2012 Aug 7.

  PMID: 22694298 BACKGROUND

• Bowling BV, Acra EE, Wang L, Myers MF, Dean GE, Markle GC, Moskalik CL, Huether CA. Development and evaluation of a genetics literacy assessment instrument for undergraduates. Genetics. 2008 Jan;178(1):15-22. doi: 10.1534/genetics.107.079533.

  PMID: 18202354 BACKGROUND

• Gray SW, Hicks-Courant K, Cronin A, Rollins BJ, Weeks JC. Physicians' attitudes about multiplex tumor genomic testing. J Clin Oncol. 2014 May 1;32(13):1317-23. doi: 10.1200/JCO.2013.52.4298. Epub 2014 Mar 24.

  PMID: 24663044 BACKGROUND

• Selim AJ, Rogers W, Qian SX, Brazier J, Kazis LE. A preference-based measure of health: the VR-6D derived from the veterans RAND 12-Item Health Survey. Qual Life Res. 2011 Oct;20(8):1337-47. doi: 10.1007/s11136-011-9866-y. Epub 2011 Feb 19.

  PMID: 21336657 BACKGROUND

MeSH Terms

Conditions

Genetic Predisposition to Disease; Disease Susceptibility; Disease Attributes; Pathologic Processes

Interventions

Exome Sequencing

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Whole Genome Sequencing; Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Results Point of Contact

• Title: Jill Robinson
• Organization: Baylor College of Medicine

jill.robinson@bcm.edu

7137985848

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Division of Genetics, Department of Medicine

Model Details: Whole exome sequencing (WES) will be performed on 75 ostensibly healthy, active-duty Airmen (patient-participants) who receive medical care in military Primary Care, Internal Medicine and/or Family Practice settings who in their baseline survey expressed interest in receiving WES. Military healthcare providers who have received brief genomics training will return results to the patient-participants and the WES reports will be permanently integrated into their electronic medical record.

Study Record Dates

• First Submitted: August 31, 2017
• First Posted: September 8, 2017
• Study Start: August 23, 2017
• Primary Completion: June 22, 2019
• Study Completion: January 11, 2020
• Last Updated: October 2, 2024
• Results First Posted: May 6, 2021

Record last verified: 2024-09

Locations

US (3)