Genetic Testing to Understand and Address Renal Disease Disparities Across the United States Pharmacogenetic Substudy (GUARDD-US PGx)

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

This is a substudy of GUARDD-US (Genetic testing to Understand and Address Renal Disease Disparities across the United States, NCT04191824). Its primary purpose is to determine the effect of knowledge of genetic test results that predict efficacy of various antihypertensive medications on change in SBP (systolic blood pressure) from baseline to 3 months in APOL1 (apolipoprotein L1) negative individuals at participating sites.

Study Overview

• Status: Completed
• Conditions: Hypertension; Chronic Kidney Disease
• Intervention / Treatment: Other: Timing of return of results

Detailed Description

GUARDD-US includes a substudy that randomizes participants in the Intervention arm who are from the PGx substudy participating sites and who test negative for APOL1 to PGx Intervention (i.e., immediate PGx ROR) and PGx Control (i.e., delayed PGx ROR) in a 1:1 ratio. This substudy will compare outcomes between participants in the PGx Control group and the PGx Intervention group.

New data show that genetic differences may cause patients to respond differently antihypertensive medication therapy. Pharmacogenomics may help guide initial or add-on antihypertensive therapy management. However, the impact of PGx testing on BP has not been studied in clinical trials among general or African ancestry populations.

Population for PGx Substudy:

Participants from Randomized Population who are randomized to Intervention and who test negative for APOL1. Only participants from PGx-substudy participating sites are included in this population.

Substudy Analyses:

Major primary 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).

• Study Type: Interventional
• Enrollment (Actual): 1874
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida - Gainesville
    • Jacksonville, Florida, United States, 32209
      • University of Florida - Jacksonville
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
    • Indianapolis, Indiana, United States, 46202
      • Eskenazi Health
  • New York
    • New York, New York, United States, 10029
      • ICAHN School of Medicine at Mount Sinai
    • New York, New York, United States, 10035
      • The Institute for Family Health
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immediate Return of Results; Immediate return of pharmacogenetic (PGx) results to substudy (APOL1 negative) participant.	Other: Timing of return of results; Participants will be randomized to immediate versus delayed return of PGx results.
Active Comparator: Delayed Return of Results; Delayed return of pharmacogenetic (PGx) results to substudy (APOL1 negative) participant until after the completion of the 6 month final study visit.	Other: Timing of return of results; Participants will be randomized to immediate versus delayed return of PGx results.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Systolic Blood Pressure From Baseline to 3 Months for APOL1 Negative Participants	Baseline to 3 month study visit

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Icahn School of Medicine at Mount Sinai; University of Florida; National Human Genome Research Institute (NHGRI); Indiana University School of Medicine
• Investigators: Study Director: Hrishikesh Chakraborty, DrPH, Duke University; Principal Investigator: Carol Horowitz, MD, ICAHN School of Medicine at Mount Sinai

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2020
• Primary Completion (Actual): April 9, 2024
• Study Completion (Actual): May 17, 2024

Study Registration Dates

• First Submitted: December 19, 2024
• First Submitted That Met QC Criteria: December 19, 2024
• First Posted (Actual): December 24, 2024

Study Record Updates

• Last Update Posted (Actual): June 17, 2025
• Last Update Submitted That Met QC Criteria: May 30, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Kidney Disease; Pharmacogenomics; Genetic testing; Hypertensive medications
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: Pro00102997_A; U01HG007269 (U.S. NIH Grant/Contract); U01HG010225 (U.S. NIH Grant/Contract); U01HG010248 (U.S. NIH Grant/Contract); U01HG010245 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Data Coordinating Center (DCC) will submit de-identified participant level datasets and associated documentation to the NHGRI's data repository - Genomic Analysis, Visualization and Informatics Lab-space (AnVIL), for use by other investigators. The datasets and associated documentation will be available after publication of the primary results manuscript. Documentation will include annotated case report forms, list of derived variables along with descriptions, and a description of the data model and de-identification process. The substudy data will be submitted within the main study complete dataset.
• IPD Sharing Time Frame: 3 months after publication
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No