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

800 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the treatment Cascade screening for high cholesterol?

Research shows that cascade screening is an effective way to identify people with familial hypercholesterolemia (a genetic condition causing high cholesterol), helping to diagnose more cases and allowing for earlier treatment. ^{1 2 3 4 5}

Is cascade screening for high cholesterol safe for humans?

The research articles do not provide specific safety data for cascade screening for high cholesterol, but they discuss the concept of prescribing cascades, where one medication leads to side effects that require additional medications. This highlights the importance of careful medication management to avoid unnecessary risks. ^{6 7 8 9 10}

How is cascade screening for high cholesterol different from other treatments?

Cascade screening is unique because it involves testing family members of someone diagnosed with familial hypercholesterolemia (a genetic condition causing high cholesterol) to find others who might have the condition. This approach focuses on early identification and prevention rather than treating symptoms after they appear. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Cascade screening for familial hypercholesterolaemia: implications of a pilot study for national screening programmes. [2022]

2. Brazil pubmed.ncbi.nlm.nih.gov

Predictors of Family Enrollment in a Genetic Cascade Screening Program for Familial Hypercholesterolemia. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Implementation of cascade testing for the detection of familial hypercholesterolaemia. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

Cascade Screening in Familial Hypercholesterolemia: Advancing Forward. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of genetic testing and cascade screening in familial hypercholesterolemia. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Modifiable statin characteristics associated with potential statin-related prescribing cascades. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Associations between statins and adverse events in secondary prevention of cardiovascular disease: Pairwise, network, and dose-response meta-analyses of 47 randomized controlled trials. [2022]

8. Argentina pubmed.ncbi.nlm.nih.gov

Prescribing cascade. A proposed new way to evaluate it. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Evaluation of a Beta-Blocker-Edema-Loop Diuretic Prescribing Cascade: A Prescription Sequence Symmetry Analysis. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

A quality-of-care analysis of cascade iatrogenesis in frail elderly hospital patients. [2019]