Clinical trial NCT06748040: Genetic Testing to Understand and Address Renal Disease Disparities Across the United States Pharmacogenetic Substudy
Official title: Genetic Testing to Understand and Address Renal Disease Disparities Across the United States - Pharmacogenetic Substudy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Disease
Hypertension
Keywords: Kidney Disease
Genetic testing
Pharmacogenomics
Hypertensive medications
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Human Genome Research Institute (NHGRI)
name: Icahn School of Medicine at Mount Sinai
name: University of Florida
name: Indiana University School of Medicine
First posted: 2024-12-24
Enrollment: 1874
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Immediate versus delayed return of pharmacogenetics (PGx) testing results to provider and participant.
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Change in Systolic Blood Pressure From Baseline to 3 Months for APOL1 Negative Participants
timeFrame: Baseline to 3 month study visit
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Gainesville
country: United States
facility: University of Florida - Gainesville
state: Florida
city: Jacksonville
country: United States
facility: University of Florida - Jacksonville
state: Florida
city: Indianapolis
country: United States
facility: Eskenazi Health
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: The Institute for Family Health
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: Duke University
name: Hrishikesh Chakraborty, DrPH
role: STUDY_DIRECTOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Carol Horowitz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.