An interventional study of Cascade screening in Familial Hypercholesterolemia, sponsored by Northwestern University. Enrolling by invitation at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-09.
Sponsored by Northwestern University · Not applicable, Interventional, and Health services research
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.
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.
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.
245 studies on the registry are indexed under Hyperlipoproteinemia Type II; 52 are open to participants now.
This study's planned enrollment of 800 is above the median of 86 across 170 interventional studies indexed under Hyperlipoproteinemia Type II.
Browse Hyperlipoproteinemia Type II studies →Northwestern University is the lead sponsor of 1,396 studies on the registry; 199 are open to participants now.
Of its 102 completed or terminated interventional studies of FDA-regulated products, 73 (72%) have results posted.
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Exclusion Criteria (probands):
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).
Behavioral: Cascade screening
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).
Behavioral: Cascade screening
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).
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.
Reach
Reach is defined as the proportion of probands who have at least one family member who completes screening (via a lipid panel or an FH genetic test) within 6 months of proband randomization. To mimic real world settings, we will allow family members to select how they would like to complete their screening from a range of mechanisms: sharing results from a recent lipid panel, requesting a lipid panel from their primary care provider, or having the study clinician order a lipid panel via LabCorp, a nationwide lab testing company.
Time frame: Collected from proband randomization date through six months post-randomization
Absolute number of family members who are screened for FH as a result of cascade screening
Absolute number of family members who are screened for FH as a result of cascade screening within 6 months of proband enrollment will be obtained through several complementary approaches: 1) self-report from the proband or from the family member; 2) confirmation of lipid testing by the study; 3) direct receipt of blood lipid panel testing from the lab when ordered by the study clinician.
Time frame: Collected from proband randomization date to six months post-randomization
Absolute number of family members who are newly diagnosed with FH as a result of cascade screening
Absolute number of family members who are newly diagnosed with FH as a result of cascade screening within 6 months of proband enrollment will be obtained through several complementary approaches: 1) self-report from the proband or from the family member; 2) confirmation of genetic testing by the study; 3) direct receipt of genetic testing from the lab when ordered by the study clinician.
Time frame: Collected from proband randomization date to six months post-randomization
LDL-C in probands
Proband LDL-C will be collected via lipid panel results obtained through two complementary approaches: 1) self-report from the proband; or 2) direct receipt of blood lipid panel testing from the lab when ordered by the study clinician.
Time frame: One-time collection at 12 months post-randomization
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