A Study Comparing Direct and Indirect Contact Methods for Genetic Cascade Screening in Adults with Familial Hypercholesterolemia and Long QT Syndrome

What this Trial Is About

This research aims to improve methods for cascade screening, which is the process of identifying and testing family members who may carry specific genetic variants linked to Long QT Syndrome and Familial Hypercholesterolemia. The study compares two approaches direct contact by the study team versus indirect contact initiated by the proband the identified individual. It also evaluates how these methods affect mental, physical, and psychosocial outcomes for both probands and their family members, while respecting privacy and communication challenges. Participants known to carry the KCNQ1 Met224Thr or APOB Arg3527Gln variants will be randomly assigned to one of two groups. In the indirect group, probands will inform their first-degree relatives about screening opportunities using provided informational materials. In the direct group, study staff will contact eligible first-degree relatives after probands are informed and have also contacted their family. Family members in both groups will receive pre-test counseling and free saliva-based genetic testing at home, followed by post-test counseling. Follow-up contact may include letters, phone calls, or home visits if family members do not respond. Throughout the study, participants will complete surveys assessing ethical views, anxiety, perceived pressure, and disease knowledge at one week after family contact and at study end. The study team will also conduct interviews to explore implementation challenges and acceptability. The main outcome measures include the proportion of first-degree relatives who undergo screening and the number of new cases detected. The estimated study duration is approximately four years, with continuous monitoring and evaluation.

Comparing Direct vs Indirect Methods for Cascade Screening