Genetic Testing to Understand and Address Renal Disease Disparities Across the United States

Study Overview
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Brief Summary
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The primary aim is to determine the effect of participant and provider knowledge of a positive APOL1 status and accompanying guideline based clinical decision support (CDS) on blood pressure management on change in systolic blood pressure (SBP) from baseline to 3 months after randomization among the APOL1 positive participants. Secondary aims are to: Determine the effect of participant and provider knowledge of a positive APOL1 status on the probability of appropriate CKD diagnosis. Determine the effect of participant and provider knowledge of a positive APOL1 status on the probability of receiving a urine microalbumin/creatinine testing and ACE-I/ARB prescription based on results of the urine microalbumin level. Explore cost effectiveness, mediators, moderators, psychobehavioral impact of results disclosure on participants, and effects of participant and provider knowledge of APOL1 status on provider treatment recommendations. PGX Substudy In addition, GUARDD-US will include a substudy to determine the effect of knowledge of genetic test results that predict efficacy of various antihypertensive medications on change in SBP from baseline to 3 months in APOL1 negative individuals. Approximately 6,650 participants of African ancestry age 18-70 with hypertension that either: 1) do not have diabetes and do not have CKD, or 2) have CKD. Participants with diabetes may be included as long as they also have CKD. Population for Main Study: Participants from Randomized Population (above) who test positive for APOL1 Population for PGx Substudy: Participants from Randomized Population (above) randomized to Intervention and who test negative for APOL1 Main Study Analyses: To determine the effect of participant and provider knowledge of a positive APOL1 status on SBP, we will compare the change in SBP from baseline to 3 months of the Intervention - APOL1 positive group to the change in SBP from baseline to 3 months of the Control - APOL1 positive group using a two sided t-test, as appropriate, with a two-sided type I error of 0.05. The effect of knowledge of a positive APOL1 status on all secondary endpoints will be compared between Intervention - APOL1 positives to Control - APOL1 positives with the proportion difference test. Additional analyses will include analysis of time trends in SBP, subset analyses, and exploratory analyses of cost effectiveness, mediators, moderators, psychobehavioral impact of results disclosure on participants, and effects of knowledge of APOL1 status on provider treatment recommendations. Substudy Analyses: All primary and secondary endpoint analyses conducted for the APOL1 main study will be repeated for the PGx substudy focusing on differences in outcomes between APOL1 negative individuals with immediate PGx ROR (PGx Intervention) and APOL1 negative individuals with delayed PGx ROR (PGx Control).

Official Title
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Genetic Testing to Understand and Address Renal Disease Disparities Across the United States

Conditions
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Renal Disease

Intervention / Treatment
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* Diagnostic Test: APOL1 status


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Self reported African ancestry English Speaking Age 18-70 years Have diagnosis of hypertension Diagnosis of hypertension is defined by either: ICD10 diagnosis codes (i.e., I10; I11.x; I12.x; I13.x; I16.x) OR On active antihypertensive therapy for indication of hypertension OR Having systolic blood pressure of 140 mm Hg or greater in at least 2 of the last 3 consecutive recorded values in the EHR OR Having hypertension in the patient's medical record problem list Have been seen at ≥1 time in past year at a participating primary care site Either: 1) do not have diabetes and do not have CKD, or 2) have CKD; Participants with diabetes may be included as long as they also have CKD. CKD is defined by either: 1) ICD10 codes (i.e., N18.x; E08.22; E09.22; E10.22; E11.22;E13.22 (exclude Z94.0; N18.6; Z99.2)) OR 15 ≤ eGFR ≤ 60 ml/min for 2 time periods ≥ 3 months Diabetes is defined by: HbA1c ≥ 6.5 at least one time in the last year OR ICD10 diagnosis codes (see Appendix A) OR Having diabetes in the patient's medical record problem list Exclusion Criteria: Have diabetes, but no CKD. Are currently on dialysis (ICD 10 codes N18.6, Z99.2 and Z94.0) Have ESRD (eGFR<15 ml/min) Have a left ventricular assist device (LVAD) Have a terminal illness Have patient-reported known pregnancy at time of enrollment Have had a liver, kidney, or bone marrow transplant Too cognitively impaired to provide informed consent and/or complete the study protocol Institutionalized or too ill to participate (i.e. incarcerated, psychiatric or nursing home facility) Plan to move out of the area within 6 months of enrollment Not a current patient seeing a provider who cares for their hypertension (i.e., family medicine, internal medicine, nephrology, HIV provider, cardiology, hypertension specialists) at a participating site Previously participated in the GUARDD pilot study OR have previously undergone APOL1 testing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Immediate versus delayed return of Apolipoprotein L1 (APOL1) gene testing results to provider and participant.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immediate Return of Results<br>Immediate return of results to inform participant of APOL1 status (either positive or negative). | Diagnostic Test: APOL1 status<br>* Participants will be randomized to immediate versus delayed return of results for positive or negative APOL1 status.<br>|
| Active Comparator: Delayed Return of Results<br>Delayed return of results of APOL1 status (either positive or negative) after the completion of the 6 month final study visit. | Diagnostic Test: APOL1 status<br>* Participants will be randomized to immediate versus delayed return of results for positive or negative APOL1 status.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in systolic blood pressure from baseline to 3 months | Change in systolic blood pressure | Baseline to 3 month study visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urine microalbuminuria/proteinuria | Change in urine microalbuminuria/proteinuria | From baseline to 6 months | 
| Appropriate order of microalbuminuria/proteinuria tests | Appropriate order of microalbuminuria/proteinuria tests | baseline to 6 months | 
| Change in appropriate diagnosis for stage 3 CKD | Change in appropriate diagnosis for stage 3 CKD | baseline to 6 months | 
| Appropriate diagnosis of CKD stage 3 and above | Appropriate diagnosis of CKD stage 3 and above | baseline to 6 months | 
| Change in appropriate diagnosis for any stage CKD | Change in appropriate diagnosis for any stage CKD | Baseline to 6 months | 
| Appropriate diagnosis of all stage CKD | Appropriate diagnosis of all stage CKD | Baseline to 6 months |