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

Sponsor
Brigham and Women's Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT03276637
Collaborator
United States Department of Defense (U.S. Fed)
93
Enrollment
3
Locations
1
Arm
28.6
Actual Duration (Months)
31
Patients Per Site
1.1
Patients Per Site Per Month

Study Details

Study Description

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
  • Genetic: Whole exome sequencing
 N/A

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.

Study Design

Study Type:
Interventional
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.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 :
Aug 23, 2017
Actual Primary Completion Date :
Jun 22, 2019
Actual Study Completion Date :
Jan 11, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Brigham and Women's Hospital Boston Massachusetts United States 02115
2 Baylor College of Medicine Houston Texas United States 77030
3 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

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

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:
Sep 8, 2017
Last Update Posted:
May 6, 2021
Last Verified:
Apr 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
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, Professor of Medicine, Division of Genetics, Department of Medicine, 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:
Disease Susceptibility
Genetic Predisposition to Disease

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Healthy Active-Duty Airmen Cohort
Arm/Group 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. 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
Period Title: Overall Study
STARTED 93
Completed Pre Survey 93
Underwent Sequencing 75
Completed Post Survey 69
COMPLETED 69
NOT COMPLETED 24

Baseline Characteristics

Arm/Group Title Healthy Active-Duty Airmen Cohort
Arm/Group 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. 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 CLIA certified laboratory on 75 enrolled individuals
Overall Participants 93
Age (Count of Participants)
<=18 years
0
0%
Between 18 and 65 years
93
100%
>=65 years
0
0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
33.75
(8.3)
Sex: Female, Male (Count of Participants)
Female
45
48.4%
Male
48
51.6%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Lation
17
18.3%
Non-Hispanic White
61
65.6%
Non-Hispanic Other
13
14%
Prefer Not to Answer
2
2.2%
Region of Enrollment (participants) [Number]
United States
93
100%

Outcome Measures

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

Outcome Measure Data

Analysis Population Description
69 participants completed follow-up survey
Arm/Group Title Healthy Active-Duty Airmen Cohort
Arm/Group Description 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 exome sequencing (ES) undergo ES and have the results returned to them.
Measure Participants 75
Baseline
2.62
(0.75)
6-weeks post-disclosure
2.66
(0.91)
2. Primary Outcome
Title Genomic Sequencing Findings
Description Analysis of whole exome sequencing results identified the number of participants with genomic findings, including monogenic disease risk, carrier status, and risk allele presence.
Time Frame Results disclosure (within 1 month of sequencing completion)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Healthy Active-Duty Airmen Cohort
Arm/Group 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. 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 CLIA certified laboratory on 75 enrolled individuals
Measure Participants 75
Present
11
11.8%
Not Present
64
68.8%
Present
65
69.9%
Not Present
10
10.8%
Present
37
39.8%
Not Present
38
40.9%
3. Primary Outcome
Title Active-duty Airmen Reported Health Care Utilization Related to Study Results
Description 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.
Time Frame 6 weeks post-disclosure (approx. 43 weeks after baseline)

Outcome Measure Data

Analysis Population Description
69 participants completed follow-up survey and several participants selected more than one answer for 83 total responses.
Arm/Group Title Healthy Active-Duty Airmen Cohort
Arm/Group 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. 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 CLIA certified laboratory on 75 enrolled individuals
Measure Participants 83
Change in diet
9
9.7%
Change in exercise
7
7.5%
Change in use of vitamin supplements
5
5.4%
Change in use of medication
5
5.4%
Other change
1
1.1%
No change
56
60.2%
4. Secondary Outcome
Title Active-duty Airmen Attitudes and Perceived Utility Toward Genomic Sequencing
Description 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.
Time Frame Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline)

Outcome Measure Data

Analysis Population Description
69 surveys completed at follow-up
Arm/Group Title Healthy Active-Duty Airmen Cohort
Arm/Group Description 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 exome sequencing (ES) undergo ES and have the results returned to them.
Measure Participants 75
Trust at baseline
14.31
(2.47)
Trust at follow-up
14.10
(2.25)
Usefulness - Baseline
7.76
(2.11)
Usefulness - follow-up
7.30
(2.11)
5. Secondary Outcome
Title Active-duty Airmen's Health Perceptions
Description 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.
Time Frame Baseline and 6-weeks post-disclosure (approx.. 43 weeks after baseline)

Outcome Measure Data

Analysis Population Description
69 surveys were completed at follow-up
Arm/Group Title Healthy Active-Duty Airmen Cohort
Arm/Group Description 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 exome sequencing (ES) undergo ES and have the results returned to them.
Measure Participants 75
Health perceptions- baseline
3.95
(0.81)
Health perceptions - follow-up
3.86
(0.76)

Adverse Events

Time Frame From baseline survey to approximately 6 weeks after disclosure (43 weeks after baseline)
Adverse Event Reporting Description Any serious adverse events linked to the disclosure of genomic information will be reported both to the Institutional Review Board (IRB) within one week of the time the event is identified. For all other metrics, the PI will review data & report annually to the IRB.
Arm/Group Title Healthy Active-Duty Airmen Cohort
Arm/Group 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. 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 CLIA certified laboratory on 75 enrolled individuals
All Cause Mortality
Healthy Active-Duty Airmen Cohort
Affected / at Risk (%) # Events
Total 0/75 (0%)
Serious Adverse Events
Healthy Active-Duty Airmen Cohort
Affected / at Risk (%) # Events
Total 0/75 (0%)
Other (Not Including Serious) Adverse Events
Healthy Active-Duty Airmen Cohort
Affected / at Risk (%) # Events
Total 0/75 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Jill Robinson
Organization Baylor College of Medicine
Phone 7137985848
Email jill.robinson@bcm.edu
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:
Sep 8, 2017
Last Update Posted:
May 6, 2021
Last Verified:
Apr 1, 2021