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

Not Applicable

Completed

Conditions: Chronic Kidney Disease
Hypertension

Interventions: Diagnostic Test: APOL1 status

Registration Number: NCT04191824

Lead Sponsor: Duke University

Brief Summary: GUARDD-US is a prospective, multicenter, unblinded, two arm randomized pragmatic clinical trial. Participants will be randomized in a 1:1 ratio to immediate APOL1 gene testing and return of results (ROR) to participant and provider (Intervention arm) versus delayed APOL1 gene testing and ROR to participant and provider (Control arm). The main study will compare outcomes between APOL1 positive participants in the Intervention arm (i.e., early knowledge of APOL1 status) to APOL1 positive participants in the Control arm (i.e., delayed knowledge of APOL1 status). Participants that are APOL1 negative in the Intervention and Control groups will not be included in the main study analyses.

GUARDD-US also includes 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 at participating sites.

This substudy is listed separately on clinicaltrials.gov as NCT06748040 and Unique Protocol ID - PRO00102997_A

Detailed Description: High-risk variants in the APOL1 gene explain approximately 70% of the excess prevalence of CKD in African Americans (AAs), conferring a 5 times higher risk for hypertensive CKD and a 10 times higher risk for ESRD. A pilot study (GUARDD), showed that returning APOL1 gene test results had a statistically significant improvement in SBP at 3 months when comparing APOL1 positives to APOL1 negatives who received their genetic testing results and when comparing APOL1 positives that received their results early to overall controls who did not receive their results until after the 3 month visit. GUARDD was not however powered to evaluate the effects of having and knowing a positive APOL1 status on outcomes for those with high risk of developing CKD (i.e., comparing outcomes for APOL1 positive patients who know their genetic risk to APOL1 positive patients who do not know their genetic risk). A broader trial is needed to better determine the importance of APOL1 gene testing for improving the testing, diagnosis, and treatment of individuals at risk of CKD.

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:

1. Determine the effect of participant and provider knowledge of a positive APOL1 status on the probability of documented CKD diagnosis.

2. 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.

3. 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.

Approximately 6,750 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

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 an overall 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 6789

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: A) ICD10 codes (i.e., N18.x; E08.22; E09.22; E10.22; E11.22;E13.22 (exclude Z94.0; N18.6; Z99.2)) OR B) Microalbumin/proteinuria level >30 mg/g for 2 time periods ≥ 3 months. Values taken within 12 months of enrollment, unless 2 values are unavailable, then review within 24 months of enrollment. OR C) 15 ≤ eGFR ≤ 60 ml/min for 2 time periods ≥ 3 months. GFRs are taken within 12 months of enrollment, unless 2 values are unavailable, then review within 24 months.

Diabetes is defined by: HbA1c ≥ 6.5 at least one time in the last year OR ICD10 diagnosis codes 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 allogeneic 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Immediate Return of Results	APOL1 status	Immediate return of results to inform participant of APOL1 status (either positive or negative).
Delayed Return of Results	APOL1 status	Delayed return of results of APOL1 status (either positive or negative) after the completion of the 6 month final study visit.

Primary Outcome Measures

Name	Time	Method
Change in Systolic Blood Pressure From Baseline to 3 Months for APOL1 Positive Participants.	Baseline to 3 month study visit

Secondary Outcome Measures

Name	Time	Method
Change in Number of Participants With Urine Microalbuminuria/Proteinuria Orders	Baseline to 6 month study visit
Number of Participants With Documented Order of Microalbuminuria/Proteinuria Tests	From baseline to 6 month study visit
Number of Participants With a Change in Documented Diagnosis for Stage 3 CKD and Above	From baseline to 6 month study visit
Number of Participants With Documented Diagnosis of CKD Stage 3 and Above	From baseline to 6 month study visit
Number of Participants With a Change in Documented Diagnosis for Any Stage CKD	From baseline to 6 month study visit
Number of Participants With Documented Diagnosis of All Stages of CKD	From baseline to 6 month study visit

Trial Locations

Locations (14): Baylor Research Institute
🇺🇸
Dallas, Texas, United States
University Medical Center New Orleans
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New Orleans, Louisiana, United States
Icahn School of Medicine at Mount Sinai
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New York, New York, United States
University of Pittsburgh
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Pittsburgh, Pennsylvania, United States
Indiana University
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Indianapolis, Indiana, United States
Meharry Medical College
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Nashville, Tennessee, United States
Nashville General Hospital
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Nashville, Tennessee, United States
Vanderbilt University Medical Center
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Nashville, Tennessee, United States
University of Florida - Gainesville
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Gainesville, Florida, United States
University of Alabama at Birmingham
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Birmingham, Alabama, United States
Eskenazi Health
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Indianapolis, Indiana, United States
University of Florida - Jacksonville
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Jacksonville, Florida, United States
The Institute for Family Health
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New York, New York, United States
Southeastern Healthcare
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Lumberton, North Carolina, United States