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Adult Patients With Undiagnosed Conditions and Their Responses to Clinically Uncertain Results From Exome Sequencing

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ClinicalTrials.gov Identifier: NCT03605004
Recruitment Status : Recruiting
First Posted : July 30, 2018
Last Update Posted : June 11, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

Brief Summary:

Background:

People with conditions that are unknown or hard to diagnose may be helped by a genetic technique. It is called exome sequencing. It helps diagnose disease by unlocking all the data in a person s genetic code. But the results from it are often unclear. Uncertain results can pose problems for doctors and patients. Researchers want to learn more about how people respond when they get uncertain results.

Objective:

To study the psychological and behavioral effects of getting uncertain results from exome sequencing.

Eligibility:

Adults who have:

Had a diagnostic odyssey for at least 6 months. An example is having clinical symptoms but no diagnosis.

And had exome sequencing to try to reach a diagnosis.

Design:

Participants will choose a date and time for their interview. They will sign a form to give consent and authorization.

Participants will fill out 2 forms. One is the Intolerance of Uncertainty Short Form Scale. The other is the Perceptions of Uncertainties in Genome Sequencing Scale.

Both scales ask about what it is like to get clinically uncertain results from exome sequencing. They focus on coping and other behavioral responses.

Participants will have a phone interview. It will last for 45-60 minutes. It will be recorded and transcribed.

At the start of the call, the researcher will review the consent form with the participant. Participants will give data such as race, education, income, and how long they have been looking for a diagnosis.

Participants will read their responses to the 2 scales during the interview.


Condition or disease
Undiagnosed Disease

Detailed Description:
Patients pursuing exome sequencing in their quest for diagnosis will most often receive a clinically uncertain result. A clinically uncertain result is a result that has some level of objective uncertainty frequently viewed by clinicians in regard to a patient s diagnosis. A clinically uncertain result can be a result that is negative, with no reportable variants, or that includes one or more variants deemed uncertain with regard to the cause of a patient s illness. Clinically uncertain results present challenges to both providers and patients in the forms of disclosing and processing uncertain health information. This exploratory study aims to seek insight into the psychological and behavioral impact of receiving clinically uncertain results from exome sequencing. Semi-structured phone interviews will be conducted with approximately 30-40 adult patients with undiagnosed conditions who have received clinically uncertain result from exome sequencing. The interviews will focus on the experience of receiving the clinically uncertain result, with emphasis on appraisal of uncertainty, coping, and other affective and behavioral responses. Interviews will be transcribed and subjected to thematic analysis. Understanding how patients with undiagnosed conditions respond to clinically uncertain results from exome sequencing may inform providers practices around informed consent for exome sequencing and the disclosure of clinically uncertain results through a greater consideration of patient concerns and challenges with adaptation. This study may also identify implications for interventions to reduce negative effects of receiving uncertain genomic information.

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Study Type : Observational
Estimated Enrollment : 250 participants
Observational Model: Other
Time Perspective: Retrospective
Official Title: Adult Patients With Undiagnosed Conditions and Their Responses to Clinically Uncertain Results From Exome Sequencing
Actual Study Start Date : August 13, 2018
Estimated Primary Completion Date : February 28, 2025
Estimated Study Completion Date : February 28, 2025

Group/Cohort
Negative
Adult patients with undiagnosed conditions who have received an uninformative negative result from exome sequence.
VUS
Adult patients with undiagnosed conditions who have received one or more variants ofuncertain significance from exome sequence.



Primary Outcome Measures :
  1. Recall and Perception [ Time Frame: Interview ]
    Extent of the patients recall of their clinically uncertain result, including their understanding of the limitations of a clinically uncertain result due to its uncertain nature. It will also explore how patients appraise the uncertainty related to their clinically uncertain result, as well as their perceptions of the relationship between their clinically uncertain result and the cause of their illness.

  2. Affective and Behavioral Responses [ Time Frame: Interview ]
    How patients describe and categorize their emotional reactions to receiving clinically uncertain result from exome sequencing. It will also explore how patients describe their behavior in response to clinically uncertain result disclosures, such as use of coping strategies and decisions to disclose their results to family and friends.



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 to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Data will be received from up to 250 potential participants, in order to do interviews with a sample of approximately 30-40 participants. Participants are adult patients with undiagnosed conditions who have received one of the most common types of clinically uncertain results (negative result or one or more variants of uncertain significance (VUSs) without a known pathogenic result) from exome sequencing. Patients will be recruited from Johns Hopkins Hospital Genetics Clinics and Kennedy Krieger Institute.
Criteria
  • INCLUSION CRITERIA:
  • Had endured a diagnostic odyssey of at least 6 months before receiving exome sequencing. A diagnostic odyssey may be defined as:

    • Having a set of clinical symptoms but no diagnosis OR
    • Having a clinical diagnosis of a broad category of disease (i.e. ataxia, muscular dystrophy) but no specific diagnosis OR
    • Having a clinical diagnosis composed of psychosomatic and/or descriptive diagnoses that individually define single symptoms or groups of symptoms (i.e. migraines, IBS, joint pain), but that do not explain the entire phenotype
  • and Had exome sequencing in an attempt to attain diagnosis
  • and Received post-test counseling for exome sequencing by a genetic counselor
  • and Received a clinically uncertain result from exome sequencing. For the purposes of this study, a clinically uncertain result is defined as one of the following options:

    • One or more VUSs
    • A negative test result (no reported variants)
  • and Result disclosure for exome sequencing occurred anywhere from 1 week to 7 years prior to being interviewed

EXCLUSION CRITERIA:

  • Exome sequencing results provided a genetic diagnosis for the patient that does not fall into one of the above inclusion categories
  • Patient was under age 18 at time of clinically uncertain result disclosure
  • Patient has a cognitive disability that prevents him/her from comprehensibly answering interview questions
  • Patient cannot speak or understand English

Patients who have since received a genetic diagnosis (from some other mechanism besides their exome sequencing test) may still participate in the study if they are able to recount their experiences around receiving this sort of exome sequencing result during the time they were undiagnosed.


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): NCT03605004


Contacts
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Contact: Lori Erby, Ph.D. (301) 443-2635 lori.erby@nih.gov

Locations
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United States, Maryland
Johns Hopkins School of Public Health Recruiting
Baltimore, Maryland, United States, 21205
Contact: Jill Owczarzak, Ph.D.    410-502-0026    jillowczarzak@jhu.edu   
Kennedy Krieger Institute Recruiting
Baltimore, Maryland, United States, 21205
Contact: Julie Cohen    443-923-9243    cohenju@kennedykrieger.org   
Sponsors and Collaborators
National Human Genome Research Institute (NHGRI)
Investigators
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Principal Investigator: Lori Erby, Ph.D. National Human Genome Research Institute (NHGRI)

Publications:
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Responsible Party: National Human Genome Research Institute (NHGRI)
ClinicalTrials.gov Identifier: NCT03605004     History of Changes
Other Study ID Numbers: 999918124
18-HG-N124
First Posted: July 30, 2018    Key Record Dates
Last Update Posted: June 11, 2019
Last Verified: June 6, 2019

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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 National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ):
Genetic Testing
Variant of Uncertain Significance
Uncertainty
Qualitative