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

Hypertension Clinical Trial

— GUARDD-US  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04191824
• Other study ID #: PRO00102997
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 10, 2020
• Est. completion date: May 15, 2024

Study information

• Verified date: April 2024
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

PGx Substudy

In addition, GUARDD-US will include 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.

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

Population for PGx Substudy:

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

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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 6754
• Est. completion date: May 15, 2024
• Est. primary completion date: May 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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:

1) ICD10 codes (i.e., N18.x; E08.22; E09.22; E10.22; E11.22;E13.22 (exclude Z94.0; N18.6; Z99.2)) OR

• 15 = eGFR = 60 ml/min for 2 time periods = 3 months

• Diabetes is defined by:

• HbA1c = 6.5 at least one time in the last year OR

• ICD10 diagnosis codes (see Appendix A) 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

Related Conditions & MeSH terms

• Hypertension
• Kidney Diseases
• Renal Disease

Intervention

Diagnostic Test:
• APOL1 status
Participants will be randomized to immediate versus delayed return of results for positive or negative APOL1 status.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Baylor Research Institute	Dallas	Texas
United States	University of Florida - Gainesville	Gainesville	Florida
United States	Eskenazi Health	Indianapolis	Indiana
United States	Indiana University	Indianapolis	Indiana
United States	University of Florida - Jacksonville	Jacksonville	Florida
United States	Southeastern Healthcare	Lumberton	North Carolina
United States	Meharry Medical College	Nashville	Tennessee
United States	Nashville General Hospital	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University Medical Center New Orleans	New Orleans	Louisiana
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

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in systolic blood pressure from baseline to 3 months for APOL1 positive participants.	Change in systolic blood pressure from baseline to 3 months for APOL1 positive participants.	Baseline to 3 month study visit
Secondary	Change in urine microalbuminuria/proteinuria orders	Change in urine microalbuminuria/proteinuria orders	From baseline to 6 month study visit
Secondary	Documented order of microalbuminuria/proteinuria tests	Documented order of microalbuminuria/proteinuria tests	From baseline to 6 month study visit
Secondary	Change in documented diagnosis for stage 3 CKD and above	Change in documented diagnosis for stage 3 CKD and above	From baseline to 6 month study visit
Secondary	Documented diagnosis of CKD stage 3 and above	Documented diagnosis of CKD stage 3 and above	From baseline to 6 month study visit
Secondary	Change in documented diagnosis for any stage CKD	Change in documented diagnosis for any stage CKD	From baseline to 6 month study visit
Secondary	Documented diagnosis of all stages of CKD	Documented diagnosis of all stages of CKD	From baseline to 6 month study visit