Cascade Screening for High Cholesterol

(NHLBI-R33 Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northwestern University

Disqualifiers: Under 18, No relative contact, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different methods to encourage family screenings for familial hypercholesterolemia (FH), a hereditary condition causing high cholesterol. Researchers compare usual care to two methods: one using Penn Medicine's automated messages and another with direct assistance from the Family Heart Foundation. The goal is to determine which method leads to more family members being screened and diagnosed. Individuals with FH who receive treatment at Penn Medicine and have contact information for at least one close family member might be suitable candidates. As an unphased trial, this study allows participants to contribute to innovative strategies that could enhance family health outcomes.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that these implementation strategies are safe for promoting family cascade screening for familial hypercholesterolemia?

Research shows that checking family members for familial hypercholesterolemia (FH) safely and effectively identifies those at risk for this genetic condition. Studies have found that examining the family members of diagnosed individuals helps identify cases earlier. Early detection allows treatment, such as starting medications, to begin sooner, reducing the risk of heart problems.

No reports indicate safety issues with this screening method. It mainly involves collecting family health history and sometimes a simple blood test. These steps are generally easy to handle and not invasive. By finding FH early, this screening helps prevent more serious health issues later, without any known risks to participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about cascade screening for high cholesterol because it introduces a proactive and interconnected approach to identifying familial hypercholesterolemia (FH), a genetic condition that often goes undiagnosed. Unlike standard care, which typically involves individual diagnosis and treatment, cascade screening leverages family connections to identify at-risk relatives early on. This method can potentially increase early detection rates by systematically reaching out to family members, offering them free FH screening. By using automated communication through systems like Penn Medicine's Way to Health platform or personalized navigator support from the Family Heart Foundation, the approach maximizes outreach efficiency and effectiveness, potentially leading to earlier interventions and better health outcomes for families affected by FH.

What evidence suggests that this trial's strategies could be effective for promoting family cascade screening for familial hypercholesterolemia?

Research has shown that testing family members for familial hypercholesterolemia (FH) is highly effective. One study found that individuals identified through family testing had significantly lower rates of heart disease caused by hardened arteries (8.2% compared to 26.3%) than those not identified this way. Another study demonstrated that family testing can help diagnose FH early by systematically checking relatives. This trial will compare different approaches to cascade screening, including Penn Medicine-mediated and Family Heart Foundation-mediated methods, to determine their effectiveness in improving health outcomes. Overall, family testing serves as a powerful tool for early detection and management of FH. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with familial hypercholesterolemia (FH) treated at Penn Medicine. They must have a cell phone or email and contact info for at least one living first-degree relative. It's not for those under 18 without these communication tools or family contacts.

Inclusion Criteria

I am 18 or older with diagnosed FH and treated at Penn Medicine.

Have contact information for at least one living, first-degree biological relative

I have a cell phone that can send texts or I can access email.

Exclusion Criteria

I am under 18 years old.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implementation Strategy

Probands receive either automated messages from Penn Medicine or direct contact from Family Heart Foundation to promote family cascade screening

6 months

Ongoing contact via text, email, or phone

Follow-up

Participants are monitored for effectiveness of the implementation strategies and proband LDL-C levels are collected

12 months

1 visit (in-person or virtual) for LDL-C collection

What Are the Treatments Tested in This Trial?

Interventions

• Cascade screening

Trial Overview

The study tests two strategies to encourage family screening for FH against usual care: an automated health system approach and a patient navigator-led strategy by the Family Heart Foundation. It measures how many relatives get screened, diagnosed, and effects on proband LDL-C levels.

How Is the Trial Designed?

Group I: Penn Medicine (health system)-mediated Experimental Treatment 1 Intervention

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 II: Family Heart Foundation-mediated Experimental Treatment 1 Intervention

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 III: Usual Care Active Control 1 Intervention

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).

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Family Heart Foundation

Collaborator

Trials

3

Recruited

1,600+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

In a study of 183 individuals with familial hypercholesterolemia (FH), key predictors for enrolling relatives in genetic screening included the index-case's LDL-cholesterol levels, their knowledge of family history of dyslipidemia, and the referral source, with those referred through a dedicated website showing higher enrollment rates.

The findings suggest that understanding the clinical and socio-economic characteristics of index-cases can help improve strategies for enrolling at-risk individuals in FH screening programs, potentially enhancing early detection and management of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of Family Enrollment in a Genetic Cascade Screening Program for Familial Hypercholesterolemia. Silva, PRS., Jannes, CE., Oliveira, TGM., et al.[2019]

Cascade testing for familial hypercholesterolaemia is shown to be cost-effective and increases the uptake of preventive measures, although its implementation is limited to a few countries due to funding and infrastructure challenges.

While statins have been effective in improving vascular function in children with familial hypercholesterolaemia, there is a lack of extensive safety data, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of cascade testing for the detection of familial hypercholesterolaemia. Hadfield, SG., Humphries, SE.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8403726/

Cost-effectiveness of cascade genetic testing for familial ...

Cascade testing was cost effective, with an average discounted cost per life year gained per person and associated confidence interval of less than $50,000, ...

2.

academic.oup.com

academic.oup.com/eurjpc/advance-article/8125662

Cascade screening in familial hypercholesterolaemia is ...

In the present study, cascade screening cases had 3.2 times less ASCVD than index cases (8.2% vs. 26.3%) and less CV risk factors at first visit ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11003060/

Family cascade screening for equitable identification ...

Family cascade screening is an evidence-based practice that can increase diagnosis and improve health outcomes but is rarely implemented in ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S2772963X24004290

IMPACT-FH Study for Implementing Innovative Family ...

An average of 1.2 strategies was selected per adult relative. Cascade testing was completed for 26.6% (144/541) of adults with at least one strategy selected, ...

5.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCGEN.119.002723

New Case Detection by Cascade Testing in Familial ...

Cascade testing enables early detection of cases through systematic family tracing. Establishment of familial hypercholesterolemia cascade ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3102597/

Cascade Screening for Familial Hypercholesterolemia (FH)

Data from the U.K. has shown that cascade screening reduces the average age at which FH patients are diagnosed [3]. Cascade screening has also ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S1933287424002228

Implementation outcomes from the IMPACT-FH study

Cascade testing can be highly effective in identifying individuals with familial hypercholesterolemia (FH) and help prevent atherosclerotic cardiovascular ...

8.

jacc.org

jacc.org/doi/10.1016/j.jacadv.2024.101201

The Power of the Pedigree: Cascade Screening in Familial ...

Cascade screening represents a simple, cost-effective method for identifying additional cases in a family. This ultimately leads to earlier diagnoses of FH.