Prospective Electronic Polygenic Risk Study - Second Phase (PEPRS2)

November 3, 2022 updated by: Ali Torkamani, Scripps Translational Science Institute
This study will investigate the role of polygenic risk scores (PRS) in preventive health.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10000

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

45 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Composite MACE in intermediate to high clinical risk population
Time Frame: 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%.
5 years post enrollment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Composite MACE in high PRS
Time Frame: 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%.
5 years post enrollment
MACE Components
Time Frame: 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%.
5 years post enrollment
Treated Glaucoma
Time Frame: 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.
5 years post enrollment
LDL-C lowering
Time Frame: 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 years post enrollment
Statin or other lipid lowering therapy initiation or intensification
Time Frame: 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%.
1 year post enrollment
Statin or other lipid lowering therapy persistence
Time Frame: 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%.
2 years post enrollment
Statin or other lipid lowering therapy adherence
Time Frame: 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%.
2 years post enrollment
Glaucoma screening
Time Frame: 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.
2 years post enrollment
Physician Utility
Time Frame: 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.
1 year

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Lifestyle changes
Time Frame: 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
6 months post enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Scripps Translational Science Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Illumina, Inc.
Optum, Inc.
Quest Diagnostics-Nichols Insitute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2023

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 15, 2025

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 15, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 29, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 13, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 4, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 7, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 3, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB-21-7860

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Research records with patient identification will be kept for 6 years after study completion. The collected data and related de-identified health information may be kept indefinitely. Record retention will comply with the specific requirements of the Scripps IRB (i.e., Scripps Research must keep HIPAA form for at least 6 years after study completion).

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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