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

NCT ID: NCT06748040

Last Updated: 2025-06-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1874 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-10
• Study Completion Date: 2024-05-17

Brief Summary

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.

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).

Conditions

Chronic Kidney Disease; Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Immediate Return of Results

Immediate return of pharmacogenetic (PGx) results to substudy (APOL1 negative) participant.

Group Type: ACTIVE_COMPARATOR

Timing of return of results

Intervention Type: OTHER

Participants will be randomized to immediate versus delayed return of PGx results.

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.

Group Type: ACTIVE_COMPARATOR

Timing of return of results

Intervention Type: OTHER

Participants will be randomized to immediate versus delayed return of PGx results.

Interventions

Timing of return of results

Participants will be randomized to immediate versus delayed return of PGx results.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Human Genome Research Institute (NHGRI)

NIH

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: collaborator

Indiana University School of Medicine

OTHER

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hrishikesh Chakraborty, DrPH

Role: STUDY_DIRECTOR

Duke University

Carol Horowitz, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Florida - Gainesville

Gainesville, Florida, United States

University of Florida - Jacksonville

Jacksonville, Florida, United States

Eskenazi Health

Indianapolis, Indiana, United States

Indiana University

Indianapolis, Indiana, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

The Institute for Family Health

New York, New York, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 35660539 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

U01HG010225

Identifier Type: NIH

Identifier Source: secondary_id

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U01HG007269

Identifier Type: NIH

Identifier Source: secondary_id

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U01HG010248

Identifier Type: NIH

Identifier Source: secondary_id

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U01HG010245

Identifier Type: NIH

Identifier Source: secondary_id

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Pro00102997_A

Identifier Type: -

Identifier Source: org_study_id