Comparing Direct vs Indirect Methods for Cascade Screening

Familial Hypercholesterolemia Clinical Trial

Official title:

Comparing Direct and Indirect Methods for Cascade Screening in Familial Hypercholesterolemia (FH) and Long QT Syndrome (LQTS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05348564
• Other study ID #: R01HL163514
• Status: Recruiting
• Phase: N/A
• Start date: May 15, 2023
• Est. completion date: March 2027

Study information

• Verified date: April 2024
• Source: University of Maryland, Baltimore
• Contact: Amber L Beitelshees, PharmD
• Phone: 410-706-0118
• Email: abeitels[@]som.umaryland.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: March 2027
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ethics
• Familial Hypercholesterolemia
• Genetic Testing
• Hypercholesterolemia
• Hyperlipoproteinemia Type II
• Long QT Syndrome
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
United States	University of Maryland Amish Research Clinic	Lancaster	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Maryland, Baltimore

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Uptake of cascade screening among all first-degree relatives	Proportion of first-degree relatives who undergo testing/All eligible first-degree relatives	Through study completion: approximately 4 years
Secondary	Number of new cases detected among all first-degree family members	New cases/All eligible first-degree family members	Through study completion: approximately 4 years
Secondary	Perceived alignment of ethical principles questionnaire	Among probands and family members	up to 6 months
Secondary	Anxiety regarding method of contact questionnaire	Among probands and family members	up to 6 months
Secondary	Perceived pressure to undergo testing/share health information questionnaire	Among probands and family members	up to 6 months
Secondary	Knowledge of disease and variant questionnaire	Among probands and family members	up to 6 months