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

Status

Completed

Phases

Unknown

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04191824

Acronym

GUARDD-US

Enrollment

6789

Registered

2019-12-10

Start date

2020-07-10

Completion date

2024-05-17

Last updated

2026-03-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Kidney Disease, Hypertension

Keywords

Kidney Disease, Genetic testing, APOL1, Genomics, Renal Disease

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.

Interventions

OTHERTiming of return of results

Participants will be randomized to immediate versus delayed APOL1 return of results

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Immediate versus delayed return of Apolipoprotein L1 (APOL1) genetic testing results to provider and participant.

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

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

Design outcomes

Primary

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

Secondary

Measure	Time frame
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

Countries

United States

Contacts

STUDY_DIRECTORHrishikesh Chakraborty, DrPH

Duke University

PRINCIPAL_INVESTIGATORCarol Horowitz, MD

Icahn School of Medicine at Mount Sinai

Participant flow

Recruitment details

Participants were recruited by providers who care for participants with hypertension (including, for example, general internists, primary care providers, and nephrologists).

Pre-assignment details

There were 6789 participants consented into the overall GUARDD-US trial. Of the 6789, 35 consented participants were not randomized into the trial and were not assigned to a treatment arm. The remaining 6754 consented participants were randomized and assigned into the treatment arms. The 6754 randomized participants will be described moving forward.

Participants by arm

Arm	Count
Immediate Return of Results Immediate return of results to inform participant of APOL1 status (either positive or negative).	3,380
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.	3,374
Total	6,754

Baseline characteristics

Characteristic	Total	Immediate Return of Results	Delayed Return of Results
Age, Continuous	54.9 years STANDARD_DEVIATION 10	54.7 years STANDARD_DEVIATION 9.9	55.4 years STANDARD_DEVIATION 10.2
Ethnicity (NIH/OMB) Hispanic or Latino	174 Participants	3 Participants	95 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6539 Participants	3281 Participants	3258 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	41 Participants	20 Participants	21 Participants
Race/Ethnicity, Customized Race American Indian or Alaska Native	19 Participants	0 Participants	9 Participants
Race/Ethnicity, Customized Race Asian	0 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized Race Black or African American	6191 Participants	457 Participants	428 Participants
Race/Ethnicity, Customized Race More than one race	374 Participants	184 Participants	190 Participants
Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander	2 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Race North African/Mediterranean	2 Participants	2 Participants	0 Participants
Race/Ethnicity, Customized Race Unknown or Not Reported	162 Participants	79 Participants	83 Participants
Race/Ethnicity, Customized Race White	0 Participants	0 Participants	0 Participants
Region of Enrollment United States	6754 Participants	3380 Participants	3374 Participants
Sex: Female, Male Female	600 Participants	2178 Participants	274 Participants
Sex: Female, Male Male	2443 Participants	160 Participants	1241 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	13 / 3,380	12 / 3,374
other Total, other adverse events	0 / 0	0 / 0
serious Total, serious adverse events	0 / 0	0 / 0