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PEPRS2: Prospective Electronic Polygenic Risk Study - Second Phase

Sponsor
Scripps Translational Science Institute (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05175651
Collaborator
Illumina, Inc. (Industry), Optum, Inc. (Industry), Quest Diagnostics-Nichols Insitute (Industry)
10,000
Enrollment
1
Arm
60
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This study will investigate the role of polygenic risk scores (PRS) in preventive health.

Condition or Disease Intervention/Treatment Phase
  • Behavioral: Genetic risk assessment
 N/A

Detailed Description

This study will investigate the role of polygenic risk scores (PRS) in preventive health. Specifically, the purpose of this study is to determine whether knowledge of the degree of coronary artery disease (CAD) genetic risk or glaucoma genetic risk, as measured and conveyed by a PRS, influences patient and physician decision-making as well as clinical outcomes during short-term (6-month / 2-year) and long-term (3-year / 5-year) follow-up. A CAD and glaucoma PRS will be calculated for all study participants, with participants randomized to receiving either their CAD or glaucoma PRS. This study design allows for causal attribution of preventive actions and clinical outcomes to the receipt and degree of genetic risk. The design is informed by a pilot (MyGeneRank) and phase 1 (PEPRS first phase) study, with the key extensions being the addition of randomization and increasing the study population size to power causal association with long-term, hard clinical outcomes.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
10000 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Prospective Electronic Polygenic Risk Study - Second Phase
Anticipated Study Start Date :
Jan 15, 2022
Anticipated Primary Completion Date :
Jan 15, 2025
Anticipated Study Completion Date :
Jan 15, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: Subjects identified by Optum Health

10,000 individuals identified by Optum Health as likely meeting inclusion criteria by claims analysis.

Behavioral: Genetic risk assessment
A coronary artery disease (CAD) and glaucoma polygenic risk scores (PRS) will be calculated for all study participants, with participants randomized to receiving either their CAD or glaucoma PRS.

Outcome Measures

Primary Outcome Measures

  1. Composite MACE in intermediate to high clinical risk population [5 years post enrollment]

    Incident MACE. Binary outcome measured at 5-years post-enrollment by EHR analysis. An interim analysis will be performed at 3-years. MACE is defined as arterial revascularization or hospitalization for unstable angina, myocardial infarction, stroke, or death from cardiovascular causes. The rate of incident MACE will be compared across CAD vs glaucoma arms overall in individuals achieving a baseline PCE≥7.5%.

Secondary Outcome Measures

  1. Composite MACE in high PRS [5 years post enrollment]

    Incident MACE. Binary outcome measured at 3- and 5-years post-enrollment by EHR analysis. The rate of incident MACE will be compared across high CAD PRS individuals receiving vs blinded to their genetic risk in individuals achieving a baseline PCE≥5%.

  2. MACE Components [5 years post enrollment]

    Incident MACE components (arterial revascularization or hospitalization for unstable angina, myocardial infarction, stroke, or death from cardiovascular causes). Binary outcomes measured at 3- and 5-years post-enrollment by EHR analysis. The rate of each incident MACE component will be compared across CAD vs glaucoma arms overall in individuals achieving a baseline PCE≥7.5%.

  3. Treated Glaucoma [5 years post enrollment]

    Incident glaucoma diagnosis with initiation of treatment. Binary outcome measured at 3- and 5-years post-enrollment by EHR analysis. Incident treated glaucoma is defined as any individual with a claim for ophthalmic surgery (laser trabeculoplasty, laser peripheral iridotomy, cycloablation) or a prescription ophthalmic solution with one or a combination of the following active ingredients: prostaglandin analogs (tafluprost, bimatoprost, latanoprostene, travaprost, latanoprost), beta blockers (timolol, levobunolol, metipranolol, betaxolol, carteolol), alpha agonists (brimonidine, apraclonidine), cholinergic agonists (pilocarpine, carbachol), carbonic anhydrase inhibitors (methazolamide, dorzolamide, brinzolamide), and/or rho kinase inhibitor (netarsudil). The rate and age of incident glaucoma diagnosis with treatment will be compared across CAD and glaucoma arms overall, as well as across high glaucoma PRS individuals receiving vs blinded to their genetic risk.

  4. LDL-C lowering [5 years post enrollment]

    Adequate LDL-C lowering. Binary outcome measured at 2-, 3-, and 5-years post enrollment by EHR entry. Adequate LDL-C lowering is defined as 30% or more reduction from baseline study measured LDL-C. The rate of adequate LDL-C lowering will be compared across CAD vs glaucoma arms overall, across high CAD PRS individuals receiving vs blinded to their genetic risk, and in association with high vs low CAD PRS in individuals receiving vs blinded to their genetic risk. Within these groups, the rate of adequate LDL-C lowering will be determined in the total population, as well as subgroups stratified by baseline PCE status. PCE strata are: <5%, 5%≤PCE<7.5%, and ≥7.5%.

  5. Statin or other lipid lowering therapy initiation or intensification [1 year post enrollment]

    New or intensified prescriptions for statins or other LDL lowering therapy. Binary outcome measured at 6-months post-enrollment by survey-based self-report and EHR analysis. A prescription is considered new if no equivalent EHR entry exists 1-year prior to enrollment. A statin prescription is considered intensified if it changes intensity tiers (high-, moderate-, and low-intensity) as described in the 2013 ACC/AHA Guidelines on the Treatment of Blood Cholesterol12. The rate of lipid lowering therapy initiation and intensification will be compared across high CAD PRS individuals receiving vs blinded to their genetic risk, and in association with high vs low CAD PRS in individuals receiving vs blinded to their genetic risk. Within these groups, the rate of statin or other lipid lowering therapy initiation or intensification will be determined in the total population, as well as subgroups stratified by baseline PCE status. PCE strata are: <5%, 5%≤PCE<7.5%, and ≥7.5%.

  6. Statin or other lipid lowering therapy persistence [2 years post enrollment]

    Statin or other lipid lowering therapy prescription renewal. Binary outcome measured at 2-years post-enrollment by EHR analysis. Statin persistence is defined as prescription renewal within 60 days of the end of the duration of an index statin prescription made after study enrollment13. The rate of lipid lowering therapy persistence will be compared across high CAD PRS individuals receiving vs blinded to their genetic risk, and in association with high vs low CAD PRS in individuals receiving vs blinded to their genetic risk. Within these groups, the rate of statin or other lipid lowering therapy persistence will be determined in the total population, as well as subgroups stratified by baseline PCE status. PCE strata are: <5%, 5%≤PCE<7.5%, and ≥7.5%.

  7. Statin or other lipid lowering therapy adherence [2 years post enrollment]

    Statin or other lipid lowering therapy prescription possession. Binary outcome measured at 2-years post-enrollment by EHR entry. Statin adherence is defined as prescription coverage of no less than 80% of the days between the index statin prescription and the end of the 2-year follow-up period13. The rate of lipid lowering therapy adherence will be compared across high CAD PRS individuals receiving vs blinded to their genetic risk, and in association with high vs low CAD PRS in individuals receiving vs blinded to their genetic risk. Within these groups, the rate of statin or other lipid lowering therapy adherence will be determined in the total population, as well as subgroups stratified by baseline PCE status. PCE strata are: <5%, 5%≤PCE<7.5%, and ≥7.5%.

  8. Glaucoma screening [2 years post enrollment]

    Adoption of glaucoma screening. Binary outcome measured at 6-months and 2-years post-enrollment by self-report electronic survey. An analysis using claims and EHR data will be conducted if the degree of missingness data (due to, e.g. uncaptured optometrist visits) is no greater than 20%. The rate of glaucoma screening will be compared across high glaucoma PRS individuals receiving vs blinded to their genetic risk, and in association with high vs normal glaucoma PRS in individuals receiving vs blinded to their genetic risk.

  9. Physician Utility [1 year]

    Physician confidence, perceived utility, and actions attributable to genomic testing. Measured at 6-months and 1-year by survey-based self-report. Physician utility is characterized using a survey. Analyses are descriptive.

Other Outcome Measures

  1. Lifestyle changes [6 months post enrollment]

    Adoption of Healthy Lifestyle. Binary outcomes derived from baseline and 6-months post-enrollment by survey-based self-report. Adoption of a healthy lifestyle is defined among individuals who self-report non-smoking, active lifestyle, or healthy diet at 6-months after initially reporting the absence of any of these healthy behaviors at baseline. These factors will be analyzed as separate binary outcomes and as a composite healthy lifestyle factor defined by an increase in the number of healthy lifestyle factors self-reported at 6-months vs baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:
45 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • 45 ≥ Age < 65

  • ASCVD Risk Score > 7.5% as defined by the standard pooled cohort equation

  • Access to and ability to use a smartphone

Exclusion Criteria:

  • Prior diagnosis of coronary disease as defined by prior myocardial infarction (STEMI or NSTEMI), or revascularization (stent or coronary artery bypass grafting)

  • Prior diagnosis or treatment of glaucoma

  • Cerebrovascular disease with history of ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting

  • Peripheral arterial disease with history of claudication, revascularization (stents or bypass)

  • Current and active high-intensity statin prescription (rosuvastatin 20 mg, rosuvastatin 40 mg, atorvastatin 40 mg and atorvastatin 80 mg)

  • Anti-PCSK9 therapy

  • Lipid apheresis therapy

  • Currently enrolled in a clinical trial for lipid lowering therapy

  • Known statin intolerance to 2 or more statins in the past

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Scripps Translational Science Institute
  • Illumina, Inc.
  • Optum, Inc.
  • Quest Diagnostics-Nichols Insitute

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Ali Torkamani, Director of Genomics and Genome Informatics, Scripps Translational Science Institute
ClinicalTrials.gov Identifier:
NCT05175651
Other Study ID Numbers:
  • IRB-21-7860
First Posted:
Jan 4, 2022
Last Update Posted:
Jan 4, 2022
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Coronary Artery Disease

Study Results

No Results Posted as of Jan 4, 2022