Genetic Risk Score Disclosure for Coronary Artery Disease

(PROACT 3 Trial)

Overseen By Roukoz Karam, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Statins, Colchicine

Disqualifiers: Cardiovascular disease, Liver disease, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how sharing a genetic risk score for coronary artery disease (CAD) affects heart health. It compares two groups: one receives their genetic risk score immediately (immediate disclosure of non-high CAD PRS), while the other waits a year (deferred disclosure of non-high CAD PRS). The aim is to determine if knowing the risk score influences heart health over a year. Ideal candidates are individuals aged 40 to 75 who regularly visit Mass General Brigham and have not been diagnosed with heart disease or are on heart medications. As an unphased trial, this study provides a unique opportunity to understand how genetic information can empower individuals to take proactive steps for better heart health.

Do I have to stop taking my current medications to join the trial?

If you are currently taking LDL cholesterol-lowering or anti-inflammatory medications, including statins or colchicine, you cannot participate in this trial.

What prior data suggests that this protocol is safe for participants?

Research has shown that sharing a low genetic risk score for coronary artery disease (CAD) is generally safe. In past studies, providing these scores did not cause any major health issues. For example, one study with individuals who did not have CAD found that informing them of their low risk score, or not informing them, did not lead to any serious health problems. This suggests that knowing one's genetic risk is usually well-tolerated.

Additionally, research indicates that individuals who learned about their risk score often adopted healthier lifestyle choices, which can support heart health. It's important to understand that a genetic risk score is merely an assessment, not a treatment, so it doesn't involve medication or procedures, reducing safety concerns. Overall, evidence suggests that participants can feel confident about the safety of learning their CAD genetic risk score. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it's exploring how sharing genetic risk scores for coronary artery disease (CAD) might impact patients. Unlike traditional treatments for CAD, which focus on managing symptoms or reducing risk through medication and lifestyle changes, this approach leverages genetic information to potentially influence patient behavior and healthcare decisions. The trial compares immediate versus deferred disclosure of non-high CAD polygenic risk scores (PRS), aiming to see if learning about one's genetic risk earlier can lead to better health outcomes. This could pave the way for more personalized and proactive healthcare strategies in the future.

What evidence suggests that this trial's treatments could be effective for maintaining cardiovascular health?

This trial will compare the effects of immediate versus deferred disclosure of non-high coronary artery disease (CAD) genetic risk scores. Research has shown that knowing a genetic risk score for heart disease can help predict heart health risks. Studies indicate that when people learn they have a high risk, they often make better lifestyle choices and may use heart medications more effectively. Participants in this trial who receive their risk score immediately may adopt more proactive health habits. Overall, this genetic risk score provides a clearer understanding of heart disease risk, helping guide better prevention and care. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

Adults aged 40-75 without cardiovascular disease or high genetic risk for coronary artery disease (CAD), not on statins, and with a recent primary care visit at Mass General Brigham can join. Excluded are those who can't hold their breath for 10 seconds, have known heart diseases, take certain cholesterol or anti-inflammatory meds, have liver issues, are pregnant/breastfeeding/planning pregnancy, cannot consent, or have contraindications to study drugs.

Inclusion Criteria

Established primary care at Mass General Brigham with at least one visit in the last 2 years

I am between 40 and 75 years old.

Exclusion Criteria

Inability to hold breath for 10 seconds

I have a high genetic risk score for coronary artery disease.

I have a known heart or blood vessel disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genotyping and Randomization

Participants undergo CAD PRS testing and are randomized to immediate or deferred disclosure groups

1 week

Intervention

Immediate disclosure group receives CAD PRS results; deferred group waits 12 months

12 months

Regular primary care visits as needed

Follow-up

Participants are monitored for changes in cardiovascular health behaviors and outcomes

12 months

At least one primary care visit

What Are the Treatments Tested in This Trial?

Interventions

• Deferred Disclosure of non-high CAD PRS
• Immediate disclosure of non-high CAD PRS

Trial Overview The trial is testing if telling people their non-high genetic risk score for CAD affects their heart health over a year compared to standard care. It involves adults without heart disease and looks at whether knowing this information helps maintain cardiovascular health.

How Is the Trial Designed?

Group I: Immediate Disclosure Experimental Treatment 1 Intervention

Participants are randomized to receive their non-high CAD PRS immediately after genotyping.

Group II: Deferred Disclosure Active Control 1 Intervention

Participants are randomized to have their non-high CAD PRS withheld for 12 months before receiving their result after the follow up period.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07087431?aggFilters=status%3A

Impact of Disclosing Coronary Artery Disease Polygenic ... The trial will assess whether disclosure of a non-high CAD PRS preserves cardiovascular health within a pre-specified 5 point non-inferiority margin. 12 months ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10150334/

Clinical utility of polygenic risk scores for coronary artery ... Among the 1,197 individuals with high PRS for CAD, a 37% reduction in cardiovascular disease risk with alirocumab was observed. The number of ...

3. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.070632

Genetic and Lifestyle Risks for Coronary Artery Disease ... We examined whether an increased genetic risk for CAD is associated with long-term risk of developing all-cause, Alzheimer's, or vascular dementia.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06542432

Utility and Effectiveness of Polygenic Risk Scoring (PRS) ... This is a 1:1 randomized controlled trial of participants with no known coronary artery disease, are not on lipid-lowering therapy, and do not have LDL-C over ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10842813/

Clinical applications of polygenic risk score for coronary artery ... Among placebo-treated individuals with CAD in a PCSK9 inhibitor trial, a high CAD PRS was associated with 1.65-fold increased risk of recurrent coronary events ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07087431?lastUpdPost=2020-10-10_

Impact of Disclosing Coronary Artery Disease Polygenic ... The trial will assess whether disclosure of a non-high CAD PRS preserves cardiovascular health within a pre-specified 5 point non-inferiority margin. 12 months ...

7. sciencedirect.com sciencedirect.com/science/article/am/pii/S0021915023052772

Clinical applications of polygenic risk score for coronary ... Prospective implementation data of CAD PRS is also starting to emerge, with early results showing positive impact on healthy behavior and LDL cholesterol ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12352389/

Genetic Risk Score Enables a Vaccine for Early Primary ... The individuals with the highest genetic risk score had the highest risk for CAD. The PRS predicted cardiac events independent of traditional ...