Comparing Direct vs Indirect Methods for Cascade Screening

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05348564
• Collaborator: (none)
• Enrollment: 200
• Arms: 2
• Anticipated Duration (Months): 53

Study Details

Study Description

Brief Summary

An important aspect of successful genomic medicine implementation is developing effective approaches for screening at-risk family members after probands are identified, also known as cascade screening. Most cascade screening studies conducted to date have been conducted outside the US, and very few studies have used a rigorous approach involving a comparator group or randomized controlled design. A major question in the field is how to most effectively implement cascade screening, given commonly cited communication barriers, while respecting privacy among probands and family members. This study will conduct a randomized controlled trial to assess direct contact of relatives by study team members vs indirect, or proband-initiated, contact. We will assess efficacy of the cascade screening intervention, patient-centered outcomes regarding mental, physical, and psychosocial outcomes in probands and family members, and implementation evaluation outcomes.

Individuals who are known to carry the KCNQ1 Met224Thr or APOB Arg3527Gln variant will be eligible to participate. After providing consent and being deemed eligible, individuals will be randomized in a 1:1 manner into the direct or indirect contact of family members arm of the study. The randomization will be stratified by variant to ensure equal representation of each variant in the study arms. Individuals in the indirect arm will be instructed to contact their first-degree family members about the opportunity to be screened. They will be provided with a disease-specific pamphlet and a family letter explaining the cascade screening. In the direct arm, probands will be advised that the study staff will be contacting their family members. They will be instructed to also contact their family members prior to the study team contacting them. Approximately two weeks after this meeting with the proband, the study staff will mail letters to eligible first-degree family members of the probands. If we do not hear back from individual family members, we will follow-up with another letter, telephone call, or home visit. The information contained in the letters will be the same information for both the direct and indirect arms of the study. All interested family members will receive pre-test counseling and free, in-home, saliva-based genetic testing, and post-test counseling.

Condition or Disease	Intervention/Treatment	Phase
Long QT Syndrome; Familial Hypercholesterolemia; Ethics; Genetic Testing	Behavioral: Direct contact of family members for cascade screening of relevant variants	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Screening
• Official Title: Comparing Direct and Indirect Methods for Cascade Screening in Familial Hypercholesterolemia (FH) and Long QT Syndrome (LQTS)
• Anticipated Study Start Date: Oct 1, 2022
• Anticipated Primary Completion Date: Mar 1, 2026
• Anticipated Study Completion Date: Mar 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Direct contact Study team contact of family members	Behavioral: Direct contact of family members for cascade screening of relevant variants; Study team members will directly contact potentially impacted family members to offer genetic testing of relevant variant.
No Intervention: Indirect contact Proband initiated contact of family members

Outcome Measures

Primary Outcome Measures

1. Uptake of cascade screening among all first-degree relatives [Through study completion: approximately 4 years]

   Proportion of first-degree relatives who undergo testing/All eligible first-degree relatives

Secondary Outcome Measures

1. Number of new cases detected among all first-degree family members [Through study completion: approximately 4 years]

   New cases/All eligible first-degree family members

2. Perceived alignment of ethical principles questionnaire [up to 6 months]

   Among probands and family members

3. Anxiety regarding method of contact questionnaire [up to 6 months]

   Among probands and family members

4. Perceived pressure to undergo testing/share health information questionnaire [up to 6 months]

   Among probands and family members

5. Knowledge of disease and variant questionnaire [up to 6 months]

   Among probands and family members

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Proband Inclusion Criteria:

• KCNQ1 Thr224Met or APOB R3527Q carrier

• 18 years or older

Proband Exclusion Criteria:

• None

Family Inclusion Criteria:

• 1st degree relative of a KCNQ1 Thr224Met or APOB Arg3527Gln carrier

Family Exclusion Criteria:

• None

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of Maryland, Baltimore

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Amber Beitelshees, Associate Professor, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT05348564
• Other Study ID Numbers: R01HL163514
• First Posted: Apr 27, 2022
• Last Update Posted: Aug 16, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Long QT Syndrome; Hyperlipoproteinemia Type II; Hypercholesterolemia; Syndrome

Study Results

No Results Posted as of Aug 16, 2022