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A Pilot Project Exploring the Impact of Whole Genome Sequencing in Healthcare

This study is enrolling participants by invitation only.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01736566
First Posted: November 29, 2012
Last Update Posted: December 29, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Human Genome Research Institute (NHGRI)
Baylor College of Medicine
Duke University
Information provided by (Responsible Party):
Robert C. Green, MD, MPH, Brigham and Women's Hospital
  Purpose
The MedSeq™ Project seeks to explore the impact of incorporating information from a patient's whole genome sequence into the practice of clinical medicine. In the extension phase of MedSeq we are attempting increase our participant diversity by increasing targeted enrollment of African/African American patient participants.

Condition Intervention
Healthy Adults (Full Study and Extension Phase) Hypertrophic Cardiomyopathy or Dilated Cardiomyopathy Other: Main Study Experimental: "Standard of Care" + Whole Genome Sequencing (Genome Report) Other: Placebo Comparator: "Standard of Care" Only

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
Official Title: The MedSeq Project Pilot Study: Integrating Whole Genome Sequencing Into the Practice of Clinical Medicine

Resource links provided by NLM:


Further study details as provided by Robert C. Green, MD, MPH, Brigham and Women's Hospital:

Primary Outcome Measures:
  • Change in Attitudes and Trust [ Time Frame: Baseline and 6-weeks post-disclosure ]
    Novel measures and adapted measures (Hall, MA, et al. 2006) will assess participants' attitudes toward genetic information and trust of their physicians and the medical system regarding interpretation and use of genetic information.

  • Change in Self Efficacy [ Time Frame: Baseline and 6-months post-disclosure ]
    Assessed through a scale developed for the Multiplex Initiative (Kaphingst, K.A., et al. 2012)

  • Change in Preferences for WGS information [ Time Frame: Baseline and 6-weeks post-disclosure ]
    Through novel survey items, participants will be asked about their preferences for the types of genetic testing results they would like to receive from their whole genome sequence and their preferences regarding their sequencing results in their medical record.

  • Change in Risk Perception [ Time Frame: Baseline, at the disclosure visit (about 1 hour after results disclosure) and 6-months post-disclosure ]
    Novel and adapted survey measures from the Multiplex Initiative will assess changes in how participants perceive their own health and risk of health conditions.

  • Change in Shared Decision Making [ Time Frame: Baseline ]
    Changes in shared decision making will be assessed through the Control Preferences Scale, a validated survey measure designed to ascertain the degree of control an individual wants to assume when decisions are being made about medical treatment. The measure will assess how patients prefer to make healthcare decisions with their doctor. This will be measured one time as a stable trait.

  • Change in Intolerance of Uncertainty [ Time Frame: Baseline and 6-months post-disclosure ]
    Changes in participants' tolerance for uncertainty will be assessed through a short version of the Intolerance of Uncertainty Scale (Carleton, 2007).

  • Change in General Anxiety and Depression [ Time Frame: Baseline and at the disclosure visit (about 1 hour after results disclosure), 6-weeks post-disclosure and 6-months post-disclosure ]
    The Hospital Anxiety and Depression Scale (HADS) scale will be administered through a survey. This is a validated scale designed to assess the participants' level of depression and anxiety through Likert-type questions. Any participant scoring >14 on the anxiety subscale or >16 on the depression subscale will be contacted by study staff for evaluation.

  • Change in Health Behaviors and Intentions [ Time Frame: Baseline and at the disclosure visit (about 1 hour after results disclosure), 6-weeks post-disclosure and 6-months post-disclosure ]
    Changes in participants' health behaviors and intentions will be assessed through novel and adapted survey measures (from the Cancer Prevention Research Center, Stages of Change Measures, 1991) asking about vitamin, supplement and medication use, insurance-purchasing behaviors, and diet, smoking and exercise practices.

  • Change in Information Seeking and Sharing [ Time Frame: Baseline, at the disclosure visit (about 1 hour after results disclosure), 6-weeks post-disclosure and 6-months post-disclosure ]
    Changes in participants' information seeking and sharing behaviors will be assessed through measures adapted from the HINTS surveys on information seeking and information sharing.

  • Changes in Genetic Literacy and Numeracy [ Time Frame: Assessing Genomic Literacy at baseline and 6-months post-disclosure. Measuring Subjective Numeracy at baseline and Objective Numeracy at post-disclosure visit (about 1 hour after results disclosure) ]
    Changes in participants' numeracy will be assessed through validated measures of objective and subjective numeracy (Lipkus et al. 2007 and Fagerlin et al. 2007), and changes in genetic literacy will be measured by survey measures adapted from the ClinSeq Study (Kaphingst K.A. et al. 2012). We are only assessing changes in Genetic Literacy. Genetic Numeracy will be measured one time as a stable trait.

  • Change in Health Care Utilization [ Time Frame: Baseline, at the disclosure visit (about 1 hour after results disclosure), 6-weeks post-disclosure, and 6-months post-disclosure ]
    Changes in participants' health care utilization will be assessed through novel and adapted measures from the Behavioral Risk Factor Surveillance System (BRFSS).

  • Change in Expectations/Perceived Utility [ Time Frame: At baseline, disclosure visit at the disclosure visit (about 1 hour after results disclosure), 6-weeks and 6-months post-disclosure ]
    Novel survey items will assess participants' expectations of the number of health conditions they will learn about through genome sequencing, and their interest in, their perceived usefulness of and their concerns about these results. Novel survey items will also assess affective forecasting. Additionally, novel survey items will assess participants' perceived utility of their results in terms of their own healthcare and planned behavior.


Secondary Outcome Measures:
  • Psychological Impact [ Time Frame: 6-weeks post-disclosure and 6-months post-disclosure ]
    Psychological impact will be assessed by a modified version of the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire.

  • Satisfaction and Decisional Regret [ Time Frame: Assessing Satisfaction with Clinician and Decisional Regret at post-disclosure visit (about 1 hour after results disclosure). Assessing Satisfaction with Information at 6-weeks post-disclosure. ]
    Participants' satisfaction with their clinician will be measured via the RIAS scale (Roter and Larson, 2002). Participants' satisfaction with the information learned from genome sequencing will be assessed with novel measures. Decisional regret will be assessed through a validated scale (Brehaut 2003).

  • Understanding and Recall [ Time Frame: Assessing Understanding of Informed Consent at baseline. Assessing Understanding of Results at post-disclosure visit at the disclosure visit (about 1 hour after results disclosure), 6-weeks post-disclosure, and 6-months post-disclosure ]
    Novel items will assess participants' understanding of their genome sequencing results. Additionally, novel items will assess participants' objective understanding of the informed consent for whole genome sequencing and adapted items will assess participants' subjective understanding of the informed consent for genome sequencing.

  • Motivations for Participation [ Time Frame: Baseline ]
    Novel survey items will ask participants about why they decided to participate in this study.


Estimated Enrollment: 220
Study Start Date: December 2011
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: "Standard of Care" + Whole Genome Sequencing
Doctors and their patients will receive a Genome Report and an Annotated Family History Report.
Other: Main Study Experimental: "Standard of Care" + Whole Genome Sequencing (Genome Report)

Doctors and their patients will receive a Genome Report and a Family History Report.

There will be two sections of the Genome Report:

  1. The General Genome Report, which will include highly penetrant disease mutations, carrier status for recessive disease, and pharmacogenetic associations.
  2. The Cardiac Risk Supplement, which will contain genetic information found in the genome regarding cardiac diseases or a risk of cardiovascular diseases that can help with the care of the patient.

Extension Phase: Experimental: "Standard of Care" + Whole Genome Sequencing (Genome Report)

*In the main study participants are are randomized between Experimental and Placebo, in the Extension phase of the study participants all are in the Experimental Arm.

Placebo Comparator: "Standard of Care" Only
Doctors and their patients will receive an Annotated Family History Report only.
Other: Placebo Comparator: "Standard of Care" Only
Doctors and their patients will receive a Family History report only

Detailed Description:

Whole genome sequencing (WGS) and whole exome sequencing (WES) services are currently available to and are being utilized by physicians and their patients in both research and clinical settings. The widespread availability and use of WGS and WES in the practice of clinical medicine is imminent. In the very near future, sequencing of individual genomes will be inexpensive and ubiquitous, and patients will be looking to the medical establishment for interpretations, insight and advice to improve their health. Developing standards and procedures for the use of WGS information in clinical medicine is an urgent need, but there are numerous obstacles related to integrity and storage of WGS data, interpretation and responsible clinical integration. MedSeq™ seeks to develop a process to integrate WGS into clinical medicine and explore the impact of doing so.

We believe that WGS will be used in many ways, including two distinct and complementary situations. In generally healthy patients, physicians will use the results of WGS to derive insight into future health risks and inform prevention and surveillance efforts, a category we refer to as General Genomic Medicine. In patients presenting with a family history or symptoms of a disease, physicians will use the results of WGS to interrogate particular sets of genes known to be associated with the disease in question, a category we refer to as Disease-Specific Genomic Medicine.

Beginning in fall 2012, we will enroll 10 primary care physicians and 100 of their healthy middle-aged patients to evaluate the use of General Genomic Medicine, and 10 cardiologists and 100 of their patients presenting with hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM) to evaluate the use of Disease-Specific Genomic Medicine. We will randomize physicians and their patients within each of the above models to receive clinically meaningful information derived from WGS versus current standard of care without the use of WGS.

MedSeq™ is comprised of three distinct but highly collaborative projects. Project 1 will enroll physicians and patients into the protocol, educate the physicians on basic genomic principles and safely monitor the use of genomic information in clinical practice. Project 2 will use a WGS analysis/interpretation pipeline to generate a genome report on each patient randomized to receive WGS in this protocol. Project 3 will examine preferences and motivations of physicians and patients enrolled, evaluate the flow and utilization of genomic information within the clinical interactions, and assess understanding, behavior, medical consequences and healthcare costs associated with the use of WGS in these models of medical practice.

In an extension phase of the study, we will 1) recruit approximately 10-15 patient-participants who self-identify as African or African American, whose physicians deem to be healthy. All will be placed in the whole genome-sequencing arm of the study. They will undergo the same activities as traditional MedSeq participants except for randomization. 2) We will conduct a targeted phenotype assessment on MedSeq Project patient-participants who are identified to have a monogenic finding. We plan to perform additional analysis by reviewing their medical records and looking specifically with their variant in mind to see if features associated with the variants were known prior to the study or were identified by further testing or by their physical during the course of the study.

This initiative will significantly accelerate the use of genomics in clinical medicine by creating and safely testing novel methods for integrating information from WGS into physicians' care of patients.

  Eligibility

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.


Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Note for Age Eligibility:

  • Cardiology patients 18 Years to 90 Years OR
  • Primary Care Patients 40 Years to 65 Years (Adult, Senior)

Inclusion Criteria:

Primary Care

  • Generally healthy (as defined by the primary care provider) adult patients at Brigham and Women's Hospital ages 40-65. All patients must be fluent in English.

Cardiology

  • Patients in the Partners Healthcare System who are 18 years or older with a diagnosis of hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM) and a family history of HCM or DCM who previously had or who are candidates for targeted HCM or DCM genetic testing through routine clinical practice within Partners. All patients must be fluent in English.

Exclusion Criteria:

Primary Care

  • Patients who do not meet the above criteria. Patients with cardiac disease or a progressive debilitating illness. Patients who are pregnant or patients whose spouses/significant others are pregnant. Patients with untreated clinical anxiety or depression (as measured by a Hospital Anxiety and Depression Scale (HADS) score > 11 administered at the baseline study visit.)

Cardiology

  • Patients who do not meet the above criteria. Patients with a progressive debilitating illness. Patients who are pregnant or patients whose spouses/significant others are pregnant. Patients with untreated clinical anxiety or depression (as measured by a Hospital Anxiety and Depression Scale (HADS) score > 11 administered at the baseline study visit.)

Extension Phase - Additional Inclusion Criteria

Part 1:

  • Above inclusion and exclusion criteria PLUS:
  • Inclusion: Self-identify as African or African American.

Part 2:

Inclusion Criteria

  • MedSeq participants determined to have a monogenic finding

Exclusion Criteria

  • Participants not previously enrolled in MedSeq Project
  • Participants not identified to have a monogenic finding
  Contacts and Locations
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): NCT01736566


Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
National Human Genome Research Institute (NHGRI)
Baylor College of Medicine
Duke University
Investigators
Principal Investigator: Robert C Green, MD, MPH Brigham and Women's Hospital
  More Information

Additional Information:
NHGRI  This link exits the ClinicalTrials.gov site

Publications:
Green RC, Rehm H, Kohane I. Clinical Genome Sequencing. Genomic and Personalized Medicine 2nd Edition: 102- 122, 2012.

Responsible Party: Robert C. Green, MD, MPH, Principal Investigator, The MedSeq Project, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01736566     History of Changes
Other Study ID Numbers: MedSeq™
U01HG006500 ( U.S. NIH Grant/Contract )
First Submitted: August 17, 2012
First Posted: November 29, 2012
Last Update Posted: December 29, 2016
Last Verified: December 2016

Keywords provided by Robert C. Green, MD, MPH, Brigham and Women's Hospital:
Primary Care
Cardiology
Hypertrophic Cardiomyopathy
Dilated Cardiomyopathy
Whole Genome Sequencing

Additional relevant MeSH terms:
Cardiomyopathies
Hypertrophy
Cardiomyopathy, Dilated
Cardiomyopathy, Hypertrophic
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Cardiomegaly
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases