GUARDD-US: Genetic Testing to Understand and Address Renal Disease Disparities Across the United States
Study Details
Study Description
Brief Summary
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:
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Determine the effect of participant and provider knowledge of a positive APOL1 status on the probability of appropriate CKD diagnosis.
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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.
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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:
- 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:
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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
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APOL1 positive group to the change in SBP from baseline to 3 months of the Control - APOL1 positive group using a two sided Mann Whitney test, as appropriate, with a two-sided type I error of 0.05.
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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.
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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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Immediate Return of Results Immediate return of results to inform participant of APOL1 status (either positive or negative). |
Diagnostic Test: APOL1 status
Participants will be randomized to immediate versus delayed return of results for positive or negative APOL1 status.
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| Active Comparator: Delayed Return of Results 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
Participants will be randomized to immediate versus delayed return of results for positive or negative APOL1 status.
|
Outcome Measures
Primary Outcome Measures
- Change in systolic blood pressure from baseline to 3 months [Baseline to 3 month study visit]
Change in systolic blood pressure
Secondary Outcome Measures
- Change in urine microalbuminuria/proteinuria [From baseline to 6 months]
Change in urine microalbuminuria/proteinuria
- Appropriate order of microalbuminuria/proteinuria tests [baseline to 6 months]
Appropriate order of microalbuminuria/proteinuria tests
- Change in appropriate diagnosis for stage 3 CKD [baseline to 6 months]
Change in appropriate diagnosis for stage 3 CKD
- Appropriate diagnosis of CKD stage 3 and above [baseline to 6 months]
Appropriate diagnosis of CKD stage 3 and above
- Change in appropriate diagnosis for any stage CKD [Baseline to 6 months]
Change in appropriate diagnosis for any stage CKD
- Appropriate diagnosis of all stage CKD [Baseline to 6 months]
Appropriate diagnosis of all stage CKD
Eligibility Criteria
Criteria
Inclusion Criteria:
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Self reported African ancestry
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English Speaking
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Age 18-70 years
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Have diagnosis of hypertension
Diagnosis of hypertension is defined by either:
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ICD10 diagnosis codes (i.e., I10; I11.x; I12.x; I13.x; I16.x) OR
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On active antihypertensive therapy for indication of hypertension OR
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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
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Having hypertension in the patient's medical record problem list
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Have been seen at ≥1 time in past year at a participating primary care site
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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:
- ICD10 codes (i.e., N18.x; E08.22; E09.22; E10.22; E11.22;E13.22 (exclude Z94.0; N18.6; Z99.2)) OR
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15 ≤ eGFR ≤ 60 ml/min for 2 time periods ≥ 3 months
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Diabetes is defined by:
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HbA1c ≥ 6.5 at least one time in the last year OR
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ICD10 diagnosis codes (see Appendix A) OR
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Having diabetes in the patient's medical record problem list
Exclusion Criteria:
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Have diabetes, but no CKD.
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Are currently on dialysis (ICD 10 codes N18.6, Z99.2 and Z94.0)
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Have ESRD (eGFR<15 ml/min)
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Have a left ventricular assist device (LVAD)
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Have a terminal illness
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Have patient-reported known pregnancy at time of enrollment
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Have had a liver, kidney, or bone marrow transplant
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Too cognitively impaired to provide informed consent and/or complete the study protocol
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Institutionalized or too ill to participate (i.e. incarcerated, psychiatric or nursing home facility)
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Plan to move out of the area within 6 months of enrollment
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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
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Previously participated in the GUARDD pilot study OR have previously undergone APOL1 testing
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Florida - Gainesville | Gainesville | Florida | United States | 32610 |
| 2 | University of Florida - Jacksonville | Jacksonville | Florida | United States | 32209 |
| 3 | Eskenazi Health | Indianapolis | Indiana | United States | 46202 |
| 4 | Indiana University | Indianapolis | Indiana | United States | 46202 |
| 5 | University Medical Center New Orleans | New Orleans | Louisiana | United States | 70112 |
| 6 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
| 7 | The Institute for Family Health | New York | New York | United States | 10035 |
| 8 | Southeastern Healthcare | Lumberton | North Carolina | United States | 28358 |
| 9 | Meharry Medical College | Nashville | Tennessee | United States | 37208 |
| 10 | Nashville General Hospital | Nashville | Tennessee | United States | 37208 |
| 11 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
| 12 | Baylor Research Institute | Dallas | Texas | United States | 75210 |
Sponsors and Collaborators
- Duke University
Investigators
- Principal Investigator: Hrishikesh Chakraborty, Duke University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PRO00102997