Penn Family Screening for Familial Hypercholesterolemia

NCT ID: NCT05750667

Last Updated: 2025-07-25

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 800 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-24
• Study Completion Date: 2027-02-28

Brief Summary

The goal of this clinical trial is to test two implementation strategies (automated health system [Penn Medicine]-mediated strategy vs. Family Heart Foundation-mediated strategy using a patient navigator) versus usual care to promote family cascade screening for familial hypercholesterolemia (FH) in Penn Medicine patients diagnosed with FH ("probands"). The main questions this study aims to answer are: (1) evaluating the effect of the three approaches on reach (proportion of probands who have at least one family member who completes screening), number of family members screened, number of family members diagnosed with FH, and proband LDL-C levels; and (2) identifying implementation strategy mechanisms focusing on health equity using mixed methods and oversampling populations that experience disparities. Participants (probands) in the active arms (health system [Penn Medicine]-mediated, Family Heart Foundation-mediated) will receive messaging that provides education about FH and provides instructions for participating in family cascade screening. A subset of probands will be invited to complete a qualitative interview about their experience receiving the implementation strategy. The research team will compare the active arms to Penn Medicine usual care for cascade screening to evaluate whether the active arms are more effective at promoting cascade screening than usual care.

Detailed Description

This project leverages Penn Medicine's and the investigative team's longstanding partnership with the Family Heart Foundation (FHF), a nonprofit research and advocacy organization, to test two promising approaches to implementing cascade screening. The study will test two patient-facing implementation strategies to increase reach of cascade screening with FH probands within Penn Medicine. This pragmatic randomized controlled trial (RCT) will test (a) a health system (Penn Medicine)-mediated strategy using automated text messages and emails, (b) an FHF-mediated strategy delivered by a navigator, and (c) the "usual care" approach. Both active strategies use centralized direct contact to relatives and behavioral economics. Specifically, we will conduct a 3-arm hybrid type III effectiveness-implementation RCT.

Aim 1: Compare the effect of the three arms on effectiveness and implementation outcomes.

• Reach (primary outcome): proportion of probands who have at least one family member who completes screening
• Absolute number of family members screened
• Absolute number of family members with a new FH diagnosis
• Proband LDL-C levels 12 months post-randomization

Aim 2: Use mixed methods to identify implementation strategy mechanisms with a focus on health equity. In Aim 2a, the researchers will conduct qualitative interviews to understand proband perspectives on mechanisms of the implementation strategies using the Consolidated Framework for Implementation Research, oversampling for populations at risk for disparities. In Aim 2b, the researchers will explore disparities quantitatively by evaluating differential strategy effectiveness by race/ethnicity and gender; and descriptively explore differential strategy effectiveness by income and medical mistrust.

Conditions

Familial Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

Penn Medicine (health system)-mediated

Probands receive automated text messages and/or emails through the Way to Health (WTH) platform containing information about FH and cascade screening from Penn Medicine, and a request to identify first-degree biological relatives. Probands choose whether to contact relatives themselves or share contact information so that automated text messages and/or emails can be sent by Penn Medicine to relatives directly via WTH. If probands opt to contact relatives themselves (self-contact), they receive tips on how to do this effectively. If probands opt for Penn Medicine to contact their relatives (direct contact), relatives receive information via WTH about FH and instructions for screening. All relatives (regardless of whether they were contacted via self-contact and direct contact) will be offered FH screening at no cost. If a proband's initial choice of outreach is not successful, they will have the option of initiating the alternate outreach approach (direct or self-contact).

Group Type: EXPERIMENTAL

Cascade screening

Intervention Type: BEHAVIORAL

FH is a genetic condition that causes high LDL cholesterol starting at birth. When one individual with FH is diagnosed, it is important that biological family members are also screened, since there is a 50% chance that each first-degree relative will have also inherited FH. More distant relatives may also have inherited FH. This evidence-based process is known as cascade screening.

Family Heart Foundation-mediated

After using WTH to conduct an identity screen and giving probands an option to opt-out of having their information shared with Family Heart Foundation (FHF), FHF reaches out directly to probands via an FHF-employed navigator. During an initial call, the navigator introduces the proband to navigation services, conducts a social history, and initiates a plan for contacting relatives. Probands choose whether to contact relatives themselves (self-contact) or have FHF contact relatives directly (direct contact). Those who choose self-contact receive personalized coaching to address barriers and concerns. For direct contact relatives, FHF will call these relatives directly. All relatives (regardless of whether they were contacted via self-contact and direct contact) will be offered FH screening at no cost. If a proband's initial choice of outreach is not successful, they will have the option of initiating the alternate outreach approach (direct or self-contact).

Group Type: EXPERIMENTAL

Cascade screening

Intervention Type: BEHAVIORAL

FH is a genetic condition that causes high LDL cholesterol starting at birth. When one individual with FH is diagnosed, it is important that biological family members are also screened, since there is a 50% chance that each first-degree relative will have also inherited FH. More distant relatives may also have inherited FH. This evidence-based process is known as cascade screening.

Usual Care

Probands randomized to this arm will not receive any contact from the research team or Family Heart Foundation regarding cascade screening (i.e., no intervention).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Cascade screening

FH is a genetic condition that causes high LDL cholesterol starting at birth. When one individual with FH is diagnosed, it is important that biological family members are also screened, since there is a 50% chance that each first-degree relative will have also inherited FH. More distant relatives may also have inherited FH. This evidence-based process is known as cascade screening.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Adults aged 18 years and older with clinically diagnosed FH who are treated within the Penn Medicine system
• Have contact information for at least one living, first-degree biological relative
• Have a cell phone with texting capabilities and/or access to email

Exclusion Criteria

• People under age 18
• Do not have contact information for at least one living, first-degree biological relative
• Do not have a cell phone with texting capabilities nor access to email

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: collaborator

Family Heart Foundation

UNKNOWN

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Rinad Beidas

Ralph Seal Paffenbarger Professor and Chair, Department of Medical Social Sciences

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Pennsylvania, Perelman School of Medicine

Philadelphia, Pennsylvania, United States

Countries

United States

References

Johnson C, Chen J, McGowan MP, Tricou E, Card M, Pettit AR, Klaiman T, Rader DJ, Volpp KG, Beidas RS. Family cascade screening for equitable identification of familial hypercholesterolemia: study protocol for a hybrid effectiveness-implementation type III randomized controlled trial. Implement Sci. 2024 Apr 9;19(1):30. doi: 10.1186/s13012-024-01355-x.

Reference Type: DERIVED

PMID: 38594685 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

SP0078729

Identifier Type: -

Identifier Source: org_study_id