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

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ClinicalTrials.gov Identifier: NCT03276637
Recruitment Status : Completed
First Posted : September 8, 2017
Results First Posted : May 6, 2021
Last Update Posted : May 6, 2021
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
Robert C. Green, MD, MPH, Brigham and Women's Hospital

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.

Condition or disease Intervention/treatment Phase
Healthy Adults Genetic Predisposition to Disease Genetic: Whole exome sequencing Not Applicable

Detailed Description:

The objective of this effort is to investigate: (a) military healthcare providers' (HCPs') genomic knowledge before and after receiving a genomic educational primer and after disclosing whole exome sequencing (WES) results to begin to assess the genomic educational needs of military HCPs; (b) active-duty Airmen's knowledge and perceptions of genomic sequencing (GS); (c) reasons why active-duty Airmen choose to participate, or not to participate, in research involving GS; (d) how WES study participants, including HCPs and sequenced active-duty Airmen (patient-participants), respond to and use WES results; (e) the collection of medical, behavioral, and healthcare utilization outcomes related to the clinical integration of WES in the military; (f) how return of WES results and integration into the Electronic Medical Record (EMR) do or do not impact perceptions of mission readiness and duty assignments. Given the lack of prior research in this area in the Air Force and the broad number of topics of interest, the aims of the study are predominantly exploratory and results may be hypothesis generating.

The MilSeq Project will be conducted in two sequential phases. Phase I of the study will recruit, consent, and enroll approximately 75 ostensibly healthy active-duty Airmen who receive medical care in military Primary Care, Internal Medicine, and/or Family Practice settings to take a baseline survey. This survey will be administered to explore active-duty Airmen's perceptions of and preferences for GS, identify motivations and barriers to active-duty Airmen participating in a WES study, and assess interest in taking part in the WES study.

Phase II of the study will recruit, consent, and enroll 75 ostensibly healthy active-duty Airmen 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 through a research study. WES will be performed on each enrolled patient-participant. The result will be disclosed by an HCP-participant and permanently integrated into the patient-participant's EMR. Phase II will also recruit 10-20 military Primary Care, Internal Medicine, and/or Family Practice HCPs and consent them to participate in the study. The HCPs will receive an educational primer in genomics and will disclose WES results to Airmen participants.

There are a number of potential benefits and challenges to incorporating genomic medicine into the military, some that are relevant to the broader civilian community, but some that are unique to this population. Some of these challenges include: (a) how GS may or may not affect the perception of fitness for duty; (b) how genomic discrimination may or may not occur in the military setting; (c) how to best deal with unanticipated findings; and (d) how genomic results can be practically integrated into a military setting. In this pilot study, these potential opportunities and challenges will be explored, which will provide a basis for future study and begin to inform decisions regarding clinical care of active-duty service members.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 93 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Health Services Research
Official Title: The MilSeq Project: Enabling Personalized Medicine Through Exome Sequencing in the U.S. Air Force
Actual Study Start Date : August 23, 2017
Actual Primary Completion Date : June 22, 2019
Actual Study Completion Date : January 11, 2020

Arm Intervention/treatment
Experimental: Healthy Active-Duty Airmen Cohort
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
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




Primary Outcome Measures :
  1. Active-duty Airmen's Perceptions About Military Use of Genomic Information to Make Career Decisions [ Time Frame: Baseline and 6 weeks post disclosure of genomic sequencing results (approx. 43 weeks after baseline) ]
    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.

  2. Genomic Sequencing Findings [ Time Frame: Results disclosure (within 1 month of sequencing completion) ]
    Analysis of whole exome sequencing results identified the number of participants with genomic findings, including monogenic disease risk, carrier status, and risk allele presence.

  3. Active-duty Airmen Reported Health Care Utilization Related to Study Results [ Time Frame: 6 weeks post-disclosure (approx. 43 weeks after baseline) ]
    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.


Secondary Outcome Measures :
  1. Active-duty Airmen Attitudes and Perceived Utility Toward Genomic Sequencing [ Time Frame: Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline) ]

    Adapted measures assessed participants' attitudes toward genetic information, trust of physicians and the military regarding use of genetic information. (Hall et al. 2006). Scores are summed, with higher scores on a 4-20 scale representing greater trust.

    A novel survey item at baseline and 6-weeks post-disclosure asked participants to rate the usefulness of whole genome sequencing results for managing health now on a 1-10 scale.


  2. Active-duty Airmen's Health Perceptions [ Time Frame: Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline) ]
    Assessed using a validated measure of subjective perceptions about health status. (Latham 2013, DeSalvo 2006). Responses are on a 1 - 5 scale, where higher scores indicate more positive responses.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Patient-Participant Inclusion Criteria:

  • 18 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

Healthcare Provider-Participant Inclusion Criterion

  • 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

Patient-Participant Exclusion Criteria:

  • Those who do not meet the above inclusion criteria
  • 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

Healthcare Provider-Participant Exclusion Criteria:

  • Providers who do not meet the above inclusion criteria
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03276637


Locations
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United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Joint Base San Antonio Lackland Air Force Base - 59th Medical Wing
San Antonio, Texas, United States, 78236
Sponsors and Collaborators
Brigham and Women's Hospital
United States Department of Defense
  Study Documents (Full-Text)

Documents provided by Robert C. Green, MD, MPH, Brigham and Women's Hospital:
Publications:
McMorrow D. The $100 genome: implications for the DoD. Technical Report. McLean, Virginia: The MITRE Corporation; 2010.
De Castro M, Biesecker LG, Turner C, et al. Genomic medicine in the military. Genomic Medicine 2016;Epub ahead of print.
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.
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
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.
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.
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. Erratum in: Am J Hum Genet. 2016 Jul 7;99(1):246.

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Responsible Party: Robert C. Green, MD, MPH, Professor of Medicine, Division of Genetics, Department of Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT03276637    
Other Study ID Numbers: The MilSeq Project
First Posted: September 8, 2017    Key Record Dates
Results First Posted: May 6, 2021
Last Update Posted: May 6, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Robert C. Green, MD, MPH, Brigham and Women's Hospital:
Whole Genome Sequencing
Whole Exome Sequencing
Military
Air Force
Disease Susceptibility
Genetic Predisposition to Disease
Disease Attributes
Pathologic Processes
Additional relevant MeSH terms:
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Disease Susceptibility
Genetic Predisposition to Disease
Disease Attributes
Pathologic Processes