- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05656261
APOL1 Genetic Testing in African Americans
APOL1 Genetic Testing in African Americans: Exploring Attitudes About Genetic Risk to Improve Comprehensive Kidney Risk Assessment for Patients and Families
Recent breakthroughs in medical genetics have discovered that a portion of kidney failure affecting the Black community is mediated by coding variants in a gene called apolipoprotein L1 (APOL1) - and that genetic variants, not race - account for increased risk. For APOL1 genetic testing to be applied in a manner that improves patient care and outcomes, more information is needed regarding associations of genotype with clinical parameters related to kidney health. Further, understanding patient perceptions about knowledge of the results of APOL1 genetic testing, and how that impacts patient engagement with management of hypertension and other renal risk factors, is urgently needed.
- In a Phase 1 pilot study, we offered APOL1 genetic testing to Black patients seen in our Hypertension and Nephrology clinics at Saint Louis University, an academic medical center that serves the local urban community, and surveyed patients on attitudes and concerns about APOL1 genetic testing. 144 participants were enrolled in Phase 1.
- In the Phase 2 study, we will advance this important work in our community by offering participation to a broader patient base, including patients seen in Internal and Family Medicine clinics, SLU Hospital, as well as to first-degree relatives and spouses of SLUCare participants. This expansion seeks to advance understanding of environment-gene interactions, improve risk prediction, and target management of potentially modifiable risk factors.
Study Overview
Status
Detailed Description
Recent recognition of coding variants in the Apolipoprotein L1 (APOL1) gene as a strong risk factor for advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD) in African Americans (AAs) has marked one of the most impactful discoveries in kidney precision medicine. It is well-established that AAs have an increased risk of kidney failure, but it now appears that at least a portion of this risk disparity is genetically mediated by APOL1 renal risk variants (RRVs). Approximately 13% of Black Americans have APOL1 high-risk genotypes (2 copies of G1, G2, or compound heterozygotes [2 RRVs]) and are at higher risk for ESKD. Importantly, APOL1 high-risk genotypes are not deterministic for kidney disease. Rather, additional genetic and/or environmental "second hits" are likely required for disease initiation and progression. These "second hits" may include environmental factors and social determinants of health, as well as biologic factors.
Supported by the Mid-America Transplant Foundation, this study seeks to assess the frequency of APOL1 RRVs in local African American patients with hypertension and to assess their attitudes about APOL1 genetic testing and the potential impact of knowing one's APOL1 genotype on hypertension and renal risk factor management through self-administered surveys.
This study is open to Black patients seen in SLUCare Nephrology, Hypertension, Internal/Family Medicine clinics, or the University hospital, as well as to first-degree relatives and household family members (e.g. spouses) of enrolled participants or previously APOL1 genotyped patients of SSM Saint Louis University Hospital and SLUCare clinic. Family-based recruitment may help discriminate impacts of genetic risk from other potential shared biologic and non-biologic risk factors, and will also broaden the reach of the project in our community.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Krista Lentine, PhD, MD
- Phone Number: 314-257-3760
- Email: krista.lentine@health.slu.edu
Study Contact Backup
- Name: Yasar Caliskan, MD
- Email: yasar.caliskan@health.slu.edu
Study Locations
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Missouri
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Saint Louis, Missouri, United States, 63104
- Recruiting
- SSM Health Saint Louis University Hospital
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Contact:
- Krista Lentine, PhD, MD
- Phone Number: 314-257-3760
- Email: krista.lentine@health.slu.edu
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Contact:
- Yasar Caliskan, MD
- Email: yasar.caliskan@health.slu.edu
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
- Black patients seen at Saint Louis University Internal Medicine, Family Medicine, Hypertension and Nephrology Clinics
- Family members on enrolled patients, including first-degree relatives and household family members (e.g. spouses). Up to 3 family members per enrolled patient may also be enrolled.
- Participation is also open to family members of SLUCare patients who have undergone APOL1 genotyping as part of clinical care (i.e., during evaluation of chronic kidney disease, including for kidney transplantation evaluation, or during living donor candidacy evaluation)
Description
Inclusion Criteria:
- Ages 18-90
- Self-Identified as Black/African American. Race will be self-identified. Patients of African ancestry who identify as multi-racial are also eligible to participate.
Exclusion Criteria:
- Cognitively impaired/unable to provide consent
- Terminally ill
- Renal replacement therapy (RRT), e.g., (but not limited to) hemodialysis, peritoneal dialysis
Study Plan
How is the study designed?
Design Details
- Observational Models: Ecologic or Community
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Adults of African or sub-Saharan ancestry
The study focuses on those who are at risk of having the APOL1 renal risk variants, which homozygous or compound heterozygous variants have been shown to lead to Chronic Kidney Disease in some of the population.
Those who are found to have this mutations are of African or sub-Saharan ancestry.
This study will include those aged 18-90 of this population.
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On day of enrollment, participants will have 1 blood sample obtained to extract DNA for determining their APOL1 genotype, and will answer a survey asking about their attitudes/beliefs on kidney disease, hypertension, and diabetes, as well as genetic testing.
Participants will receive their results via telephone shortly thereafter, and then complete the same survey at 3 months and 12 months post-enrollment, in order to evaluate if any of their attitudes or beliefs have changed since knowing their APOL1 genetic test result.
Those who are interested, specifically those who carry the homozygous or compound heterozygous renal risk variant, will have the option to speak with a designated genetic counselor who is associated with the study site and approved by the IRB.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determine frequency of APOL1 renal risk variants in black population
Time Frame: 1 year
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To assess the frequency and sociodemographic/clinical correlates of APOL1 renal risk variants in a local urban population of Black patients seen in Nephrology, Hypertension, Internal/Family Medicine clinics, or University Hospital.
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1 year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determine frequency of first degree relatives of enrolled participants with APOL1 renal risk variants
Time Frame: 1 year
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To assess the association and interaction between potential "second hits" such as environmental factors and comorbidities with APOL1 genotype on kidney function among Black patients and their families.
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1 year
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Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, Bernhardy AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays E, Pollak MR. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010 Aug 13;329(5993):841-5. doi: 10.1126/science.1193032. Epub 2010 Jul 15.
- Friedman DJ, Kozlitina J, Genovese G, Jog P, Pollak MR. Population-based risk assessment of APOL1 on renal disease. J Am Soc Nephrol. 2011 Nov;22(11):2098-105. doi: 10.1681/ASN.2011050519. Epub 2011 Oct 13.
- Anyaegbu EI, Shaw AS, Hruska KA, Jain S. Clinical phenotype of APOL1 nephropathy in young relatives of patients with end-stage renal disease. Pediatr Nephrol. 2015 Jun;30(6):983-9. doi: 10.1007/s00467-014-3031-0. Epub 2014 Dec 23.
- Freedman BI, Langefeld CD, Turner J, Nunez M, High KP, Spainhour M, Hicks PJ, Bowden DW, Reeves-Daniel AM, Murea M, Rocco MV, Divers J. Association of APOL1 variants with mild kidney disease in the first-degree relatives of African American patients with non-diabetic end-stage renal disease. Kidney Int. 2012 Oct;82(7):805-11. doi: 10.1038/ki.2012.217. Epub 2012 Jun 13.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Urologic Diseases
- Disease Attributes
- Renal Insufficiency
- Disease Susceptibility
- Chronic Disease
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Kidney Diseases
- Renal Insufficiency, Chronic
- Genetic Predisposition to Disease
Other Study ID Numbers
- 29188
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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