Clinical trial NCT01736566: A Pilot Project Exploring the Impact of Whole Genome Sequencing in Healthcare
Official title: The MedSeq Project Pilot Study: Integrating Whole Genome Sequencing Into the Practice of Clinical Medicine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Adults (Full Study and Extension Phase)
Hypertrophic Cardiomyopathy or Dilated Cardiomyopathy
Keywords: Primary Care
Cardiology
Hypertrophic Cardiomyopathy
Dilated Cardiomyopathy
Whole Genome Sequencing
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Human Genome Research Institute (NHGRI)
name: Baylor College of Medicine
name: Duke University
First posted: 2012-11-29
Enrollment: 213
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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.

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 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

Primary outcomes:
measure: Change in Attitudes and Trust
timeFrame: Change at 6-weeks post-results disclosure relative to baseline, administered approx.12.5 months after baseline
measure: Change in Self Efficacy
timeFrame: Baseline and 6-months post-results disclosure (6 mos. follow-up administered approx. 17 months after baseline)
measure: Change in Preferences for WGS Information
timeFrame: Baseline and 6-weeks post-disclosure (6 wks follow-up administered approx. 12.5 mos. after baseline)
measure: Change in Perceived Health
timeFrame: Baseline, at the disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline) and 6-months post-disclosure (6 mos. follow-up follow-up administered approx. 17 months after baseline)
measure: Change in Shared Decision Making
timeFrame: Baseline and 6-weeks post-disclosure (6 wks follow-up administered approx. 12.5 mos. after baseline)
measure: Change in Intolerance of Uncertainty
timeFrame: Baseline and 6-months post-disclosure (6 mos. follow-up administered approx. 17 mos. after baseline)
measure: Change in General Anxiety and Depression
timeFrame: Baseline, at the disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline), 6-weeks post-disclosure and 6-months post-disclosure (6 wks. follow-up administered approx. 12.5 mos and 6 mos follow-up approx 17 mos. after baseline)
measure: Change in Health Behaviors
timeFrame: 6-weeks post-disclosure and 6-months post-disclosure (6 wks. follow-up administered approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)
measure: Information Sharing
timeFrame: At the disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline) and 6-months post-disclosure (approx. 17 mos. after baseline)
measure: Changes in Genomic Literacy
timeFrame: Assessing Genomic Literacy at baseline and 6-months post-disclosure (approx. 17 mos. after baseline)
measure: Changes in Health Care Utilization
timeFrame: 6 months prior to disclosure and 6-months post-disclosure (approx. 17 mos. after baseline) and 5-years post-disclosure
measure: Change in Perceived Utility
timeFrame: At baseline and 6-months post-disclosure (approx. 17 mos. after baseline)
Secondary outcomes:
measure: Psychological Impact
timeFrame: 6-weeks post-disclosure and 6-months post-disclosure (6wks. follow-up administered approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)
measure: Decisional Regret
timeFrame: At post-disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline), at 6-weeks post-disclosure, and at 6-months post-disclosure (6 wks follow-up approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)
measure: Understanding
timeFrame: At post-disclosure visit (about 1 hour after results disclosure, avg. 11 mos. after baseline), at 6-weeks post-disclosure, and at 6-months post-disclosure (6 wks follow-up approx. 12.5 mos. and 6 mos. follow-up approx. 17 mos. after baseline)
measure: Expectations
timeFrame: Baseline
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Robert C Green, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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