KCNQ1 Cascade Screening

A Community-Based Approach to Overcoming Barriers to Cascade Screening for Long QT Syndrome

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.

Study Overview

• Status: Terminated
• Conditions: Long QT Syndrome
• Intervention / Treatment: Genetic: Simplified Cascade Screening

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17602
      • University of Maryland Amish Research Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• KCNQ1Thr224Met proband or first degree family member

Exclusion Criteria:

• Family members who have not been contacted by probands

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simplified Cascade Screening; Free, mail-in, saliva-based screening for the KCNQ1 Thr224Met variant.	Genetic: Simplified Cascade Screening; Screening of the KCNQ1 Thr224Met variant for family members of probands

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of At-risk Family Members Who Underwent Cascade Screening	Rate of uptake of cascade screening after the intervention ('simplified')	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extent of Disclosure Determined by Questionnaire	proportion of family members told after the intervention ('simplified')	18 months
Number of Informed Relatives Screened Determined by Questionnaire	Number of informed family members tested after the intervention ('simplified')	18 months
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.	18 months

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: National Human Genome Research Institute (NHGRI)

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2019
• Primary Completion (Actual): April 27, 2021
• Study Completion (Actual): December 29, 2022

Study Registration Dates

• First Submitted: December 18, 2018
• First Submitted That Met QC Criteria: December 20, 2018
• First Posted (Actual): December 21, 2018

Study Record Updates

• Last Update Posted (Actual): June 27, 2023
• Last Update Submitted That Met QC Criteria: June 2, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Social; Screening; Cascade; Ethical; Legal
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Congenital Abnormalities; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Syndrome; Long QT Syndrome
• Other Study ID Numbers: HP-00081981; R21HG010412 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No