Long QT Syndrome
Conditions
Keywords
Cascade, Screening, Ethical, Legal, Social
Brief summary
The objectives of the protocol are to: (1) evaluate the uptake of cascade screening and preventative therapies after the implementation of a simplified screening process and (2) assess proband and family member perspectives about the return of research results and cascade screening for the KCNQ1 Thr224Met variant. The investigators will conduct a mixed methods study in the Old Order Amish community where the KCNQ1 variant is enriched over 100,000-fold compared to other populations. The intervention will offer free, mail-in, saliva-based genetic testing for family members of probands. The rate of uptake of testing and preventative therapy after the intervention is implemented (i.e. when 'simplified' free, mail-in, saliva-based testing was available) will be compared to data from before the intervention (i.e. when 'traditional' $50 blood-based testing was available to family members) when uptake was essentially zero. The primary outcome is the rate of uptake of cascade screening with the intervention ('simplified'). The secondary outcomes include: extent of disclosure of genotype results before and after the intervention, proportion of informed relatives who get screened before and after the intervention, and the uptake of appropriate preventative care (e.g. seeing a cardiologist and/or taking beta-blocker). The tertiary outcomes are demographic characteristics associated with uptake of cascade screening or uptake of preventative therapy. The investigators will also assess qualitative themes surrounding the return of results process and cascade screening using interviews.
Interventions
GENETICSimplified Cascade Screening
Screening of the KCNQ1 Thr224Met variant for family members of probands
Sponsors
National Human Genome Research Institute (NHGRI)
University of Maryland, Baltimore
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* KCNQ1Thr224Met proband or first degree family member
Exclusion criteria
* Family members who have not been contacted by probands
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of At-risk Family Members Who Underwent Cascade Screening | 18 months | Rate of uptake of cascade screening after the intervention ('simplified') |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Extent of Disclosure Determined by Questionnaire | 18 months | proportion of family members told after the intervention ('simplified') |
| Number of Informed Relatives Screened Determined by Questionnaire | 18 months | Number of informed family members tested after the intervention ('simplified') |
| Number of Participants With an Uptake of Preventative Therapy as Determined by Questionnaire | 18 months | Uptake of preventative therapy was defined as those taking a beta-blocker if recommended or those who implemented lifestyle modifications if beta-blocker not recommended. The survey was mailed to all probands. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Simplified Cascade Screening Free, mail-in, saliva-based screening for the KCNQ1 Thr224Met variant.
Simplified Cascade Screening: Screening of the KCNQ1 Thr224Met variant for family members of probands | 131 |
| Total | 131 |
Baseline characteristics
| Characteristic | Simplified Cascade Screening |
|---|---|
| Age, Categorical <=18 years | 88 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants |
| Age, Continuous | 19 years STANDARD_DEVIATION 17 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 131 Participants |
| Region of Enrollment United States | 131 participants |
| Sex: Female, Male Female | 59 Participants |
| Sex: Female, Male Male | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 131 |
| other Total, other adverse events | 0 / 131 |
| serious Total, serious adverse events | 0 / 131 |
Outcome results
Primary
Percentage of At-risk Family Members Who Underwent Cascade Screening
Rate of uptake of cascade screening after the intervention ('simplified')
Time frame: 18 months
Population: 809 family members were eligible to be screened and were considered at-risk.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Simplified Cascade Screening | Percentage of At-risk Family Members Who Underwent Cascade Screening | 131 Participants |
Secondary
Extent of Disclosure Determined by Questionnaire
proportion of family members told after the intervention ('simplified')
Time frame: 18 months
Population: Because of COVID, too much time had passed since we had originally contacted the probands and we did not think we could get reliable data on how many family members they had told after the intervention. Thus, these data were not collected. During the COVID pandemic we had to switch gears and warn people with LQTS about the risks of QT-prolongation with chloroquine, hydroxychloroquine, and azithromycin.
Secondary
Number of Informed Relatives Screened Determined by Questionnaire
Number of informed family members tested after the intervention ('simplified')
Time frame: 18 months
Population: Number of family members tested of those mailed letters. The overall number of participants analyzed differs from the number in the Participant Flow Module because it represents the number of family members who were mailed letters whereas the participant flow module includes individuals who consented for testing. These numbers are not related to each other because we didn't mail letters to children, although children were eligible for testing.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Simplified Cascade Screening | Number of Informed Relatives Screened Determined by Questionnaire | 27 Participants |
Secondary
Number of Participants With an Uptake of Preventative Therapy as Determined by Questionnaire
Uptake of preventative therapy was defined as those taking a beta-blocker if recommended or those who implemented lifestyle modifications if beta-blocker not recommended. The survey was mailed to all probands.
Time frame: 18 months
Population: We analyzed the number of survey responses obtained for the questions on beta-blocker therapy and lifestyle modifications which is why the numbers are different than those reported in the participant flow module.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Simplified Cascade Screening | Number of Participants With an Uptake of Preventative Therapy as Determined by Questionnaire | 6 Participants |