Undiagnosed DiseaseNCT03605004
Adult Patients With Undiagnosed Conditions and Their Responses to Clinically Uncertain Results From Exome Sequencing
An observational study of Undiagnosed Disease, run by National Human Genome Research Institute (NHGRI) at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Undiagnosed Disease
- How many people
- 26 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Aug 2018to 7 May 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Johns Hopkins School of Public Health
Baltimore, Maryland, 21205
Kennedy Krieger Institute
Baltimore, Maryland, 21205
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Undiagnosed Disease
- Keywords
- Genetic Testing, Variant of Uncertain Significance, Uncertainty, Qualitative
- Medical subject headings
- Undiagnosed Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recall and Perception
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.
Measured: Interview
Affective and Behavioral Responses
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.
Measured: Interview
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2018
- Study start13 Aug 2018
- Primary completion7 May 2020
- Study completion7 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Undiagnosed DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Retrospective
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lori Erby, Ph.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03605004
- Sponsor's protocol ID
- 999918124
- Other IDs
- 18-HG-N124
- Status last verified
- May 2020
- First submitted
- 27 Jul 2018
- Last updated
- 11 May 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Vos J, Otten W, van Asperen C, Jansen A, Menko F, Tibben A. The counsellees' view of an unclassified variant in BRCA1/2: recall, interpretation, and impact on life. Psychooncology. 2008 Aug;17(8):822-30. doi: 10.1002/pon.1311.
PubMed 18157792Han PKJ, Umstead KL, Bernhardt BA, Green RC, Joffe S, Koenig B, Krantz I, Waterston LB, Biesecker LG, Biesecker BB. A taxonomy of medical uncertainties in clinical genome sequencing. Genet Med. 2017 Aug;19(8):918-925. doi: 10.1038/gim.2016.212. Epub 2017 Jan 19.
PubMed 28102863Skinner D, Raspberry KA, King M. The nuanced negative: Meanings of a negative diagnostic result in clinical exome sequencing. Sociol Health Illn. 2016 Nov;38(8):1303-1317. doi: 10.1111/1467-9566.12460. Epub 2016 Aug 19.
PubMed 27538589
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adult Patients With Undiagnosed Conditions and Their Responses to Clinically Uncertain Results From Exome Sequencing
- ClinicalTrials.gov ID
- NCT03605004
- Acronym / sponsor ID
- 999918124
- Conditions
- Undiagnosed Disease
- Keywords
- Genetic Testing, Variant of Uncertain Significance, Uncertainty, Qualitative
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 13 Aug 2018 (actual)
- Primary completion
- 7 May 2020 (actual)
- Study completion
- 7 May 2020 (actual)
- First posted
- 30 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Other
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (10 listed)
- Had endured a diagnostic odyssey of at least 6 months before receiving exome sequencing. A diagnostic odyssey may be defined as:
- 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:
- and Result disclosure for exome sequencing occurred anywhere from 1 week to 7 years prior to being interviewed
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2020.
- Background: PubMed 18157792Vos J, Otten W, van Asperen C, Jansen A, Menko F, Tibben A. The counsellees' view of an unclassified variant in BRCA1/2: recall, interpretation, and impact on life. Psychooncology. 2008 Aug;17(8):822-30. doi: 10.1002/pon.1311.
- Background: PubMed 28102863Han PKJ, Umstead KL, Bernhardt BA, Green RC, Joffe S, Koenig B, Krantz I, Waterston LB, Biesecker LG, Biesecker BB. A taxonomy of medical uncertainties in clinical genome sequencing. Genet Med. 2017 Aug;19(8):918-925. doi: 10.1038/gim.2016.212. Epub 2017 Jan 19.
- Background: PubMed 27538589Skinner D, Raspberry KA, King M. The nuanced negative: Meanings of a negative diagnostic result in clinical exome sequencing. Sociol Health Illn. 2016 Nov;38(8):1303-1317. doi: 10.1111/1467-9566.12460. Epub 2016 Aug 19.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lori Erby, Ph.D. principal investigator
National Human Genome Research Institute (NHGRI)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Undiagnosed Disease, run by National Human Genome Research Institute (NHGRI) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recall and Perception (time frame: Interview). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03605004, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2020.