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

NCT04191824 | Completed Results DMC

• 7 other identifiers: PRO00102997U01HG010225U01HG007269U01HG010232U01HG010248U01HG010231U01HG010245
• Study Type: interventional
• Target: 6,789
• Locations: 1 country
• Sites: 14

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

Conditions

Chronic Kidney Disease; Hypertension

Keywords

Kidney Disease; Genetic testing; APOL1; Genomics; Renal Disease

Outcome Measures

Primary Outcomes (1)

• Change in Systolic Blood Pressure From Baseline to 3 Months for APOL1 Positive Participants.

  Baseline to 3 month study visit

Secondary Outcomes (6)

• 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

Study Arms (2)

Immediate Return of Results

ACTIVE COMPARATOR

Immediate return of results to inform participant of APOL1 status (either positive or negative).

Other: Timing of return of results

Delayed Return of Results

ACTIVE COMPARATOR

Delayed return of results of APOL1 status (either positive or negative) after the completion of the 6 month final study visit.

Other: Timing of return of results

Interventions

Timing of return of results OTHER

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

Delayed Return of Results; Immediate Return of Results

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• National Human Genome Research Institute (NHGRI): collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• University of Florida: collaborator
• Indiana University School of Medicine: collaborator
• Vanderbilt University Medical Center: collaborator

Study Sites (14)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of Florida - Gainesville

Gainesville, Florida, 32610, United States

Location

University of Florida - Jacksonville

Jacksonville, Florida, 32209, United States

Location

Eskenazi Health

Indianapolis, Indiana, 46202, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

The Institute for Family Health

New York, New York, 10035, United States

Location

Southeastern Healthcare

Lumberton, North Carolina, 28358, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Meharry Medical College

Nashville, Tennessee, 37208, United States

Location

Nashville General Hospital

Nashville, Tennessee, 37208, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor Research Institute

Dallas, Texas, 75210, United States

Location

Related Publications (2)

• Eadon MT, Cavanaugh KL, Orlando LA, Christian D, Chakraborty H, Steen-Burrell KA, Merrill P, Seo J, Hauser D, Singh R, Beasley CM, Fuloria J, Kitzman H, Parker AS, Ramos M, Ong HH, Elwood EN, Lynch SE, Clermont S, Cicali EJ, Starostik P, Pratt VM, Nguyen KA, Rosenman MB, Calman NS, Robinson M, Nadkarni GN, Madden EB, Kucher N, Volpi S, Dexter PR, Skaar TC, Johnson JA, Cooper-DeHoff RM, Horowitz CR; GUARDD-US Investigators. Design and rationale of GUARDD-US: A pragmatic, randomized trial of genetic testing for APOL1 and pharmacogenomic predictors of antihypertensive efficacy in patients with hypertension. Contemp Clin Trials. 2022 Aug;119:106813. doi: 10.1016/j.cct.2022.106813. Epub 2022 Jun 1.

  PMID: 35660539 BACKGROUND

• Eadon MT, Cavanaugh KL, She L, Steen-Burrell KA, Mohottige D, Nadkarni GN, Kitzman H, Chakraborty H, Empey PE, Limdi NA, Singh R, Beasley CM, Parker AS, Cicali EJ, Ramos MA, Clermont S, Dodgen L, Elwood EN, Robinson M, Umeukeje EM, Garcia Ortega A, Shroff N, Rosenman MB, Nguyen KA, Volpi S, Rider R, Dexter PR, Skaar TC, Peterson JF, Cavallari LH, Johnson JA, Wyatt CM, Orlando LA, Cooper-DeHoff RM, Horowitz CR; Implementing Genomics in Practice (IGNITE) Pragmatic Trials Network. Genetic Testing for APOL1 in Adults With Hypertension: The GUARDD-US Randomized Clinical Trial. JAMA Netw Open. 2026 Mar 2;9(3):e260528. doi: 10.1001/jamanetworkopen.2026.0528.

  PMID: 41784962 RESULT

Related Links

• Genetic Testing for APOL1 in Adults With Hypertension: The GUARDD-US Randomized Clinical Trial

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hypertension; Kidney Diseases

Condition Hierarchy (Ancestors)

Renal Insufficiency; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Hrishikesh Chakraborty, PhD
• Organization: Duke University

hrishikesh.chakraborty@duke.edu

919-668-1238

Study Officials

• Hrishikesh Chakraborty, DrPH

  Duke University

  STUDY DIRECTOR

• Carol Horowitz, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 10, 2019
• Study Start: July 10, 2020
• Primary Completion: April 9, 2024
• Study Completion: May 17, 2024
• Last Updated: March 25, 2026
• Results First Posted: April 30, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 3 months after publication
• Access Criteria: Datasets will be designated as controlled access and researchers will be able to apply to NIH data access committees (DACs) for use of these datasets.

Locations

US (14)