Familial HypercholesterolemiaNHLBI-R33NCT05750667
Penn Family Screening for Familial Hypercholesterolemia
A study testing Cascade screening in people with Familial Hypercholesterolemia, run by Northwestern University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Familial Hypercholesterolemia
- What is being tested?
- Cascade screening
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 800 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jan 2023to 28 Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of Pennsylvania, Perelman School of Medicine
Philadelphia, Pennsylvania, 19104
About this study
Official title: Leveraging Behavioral Economics to Equitably Implement Cascade Screening in Individuals With Familial Hypercholesterolemia in Partnership With the FH Foundation (R33 Phase)
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.
Read the 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
- Being tested
- Cascade screening
- Keywords
- implementation science, behavioral economics, equity, cascade screening
- Medical subject headings
- Hyperlipoproteinemia Type II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cascade screeningBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Penn Medicine (health system)-mediated | Experimental | 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). Receives: Behavioral: Cascade screening |
| Family Heart Foundation-mediated | Experimental | 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). Receives: Behavioral: Cascade screening |
| Usual Care | No 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Collected from proband randomization date through six months post-randomization
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: One-time collection at 12 months post-randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2023
- Study start24 Jan 2023
- Primary completion28 Feb 2027 (estimated)
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Familial HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Probands will be randomized to one of the two active implementation strategy arms (Penn Medicine, Family Heart Foundation; n=220 each) or usual care (n=360).
- Masking
- None (open label)
- Enrolment
- 800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pennsylvania, Family Heart Foundation
- Responsible party
- Principal investigator, Rinad Beidas, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05750667
- Sponsor's protocol ID
- SP0078729
- Acronym
- NHLBI-R33
- Status last verified
- Feb 2026
- First submitted
- 15 Feb 2023
- Last updated
- 9 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 38594685
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Leveraging Behavioral Economics to Equitably Implement Cascade Screening in Individuals With Familial Hypercholesterolemia in Partnership With the FH Foundation (R33 Phase)
- ClinicalTrials.gov ID
- NCT05750667
- Acronym / sponsor ID
- NHLBI-R33 / SP0078729
- Conditions
- Familial Hypercholesterolemia
- Keywords
- implementation science, behavioral economics, equity, cascade screening
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- University of Pennsylvania, Family Heart Foundation
- Study start
- 24 Jan 2023 (actual)
- Primary completion
- 28 Feb 2027 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 2 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Probands will be randomized to one of the two active implementation strategy arms (Penn Medicine, Family Heart Foundation; n=220 each) or usual care (n=360).
| Arm | Type | Receives |
|---|---|---|
| Penn Medicine (health system)-mediated | Experimental | Behavioral: Cascade screeningProbands 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). |
| Family Heart Foundation-mediated | Experimental | Behavioral: Cascade screeningAfter 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). |
| Usual Care | No 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 may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cascade screeningFH 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. | Behavioural | Family Heart Foundation-mediated, Penn Medicine (health system)-mediated |
Primary outcome
Reach
Time frame: Collected from proband randomization date through six months post-randomization
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.
3 secondary outcomes
Absolute number of family members who are screened for FH as a result of cascade screening
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
Time frame: Collected from proband randomization date to six months post-randomization
LDL-C in probands
Time frame: One-time collection at 12 months post-randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2026.
- Derived from this study: PubMed 38594685Johnson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cascade screening in people with Familial Hypercholesterolemia, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 9 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reach (time frame: Collected from proband randomization date through six months post-randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05750667, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2026.