Clinical trial NCT04910867: APOL1 Genetic Testing Program for Living Donors
Official title: Integrating a Culturally Competent APOL1 Genetic Testing Program Into Living Donor Evaluation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Kidney Diseases
Apolipoprotein L1
Kidney Transplantation
Keywords: Genetics
Implementation research
Healthcare disparities
Ethics
Informed consent
Safety
African continental ancestry group
genetic counseling
Culturally competent care
Electronic health records
Decision support systems, clinical
Decision making
Live kidney donation
Shared decision making
Artificial intelligence
Surveys and questionnaires
Qualitative research
Clinical trial
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Georgetown University
First posted: 2021-06-02
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: A non-randomized, pre-post design. Data will be collected from participants at both sites during a control period, prior to implementing the intervention, and during an intervention period, under the proposed APOL1 genetic testing program.
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Living donor (LD) kidney transplantation is the optimal treatment for patients with end-stage kidney disease (ESKD). However, LDs take on a higher risk of future ESKD themselves. African American (AA) LDs have an even greater, 3.3-fold, risk of ESKD than white LDs post-donation. Because evidence suggests that Apolipoprotein L1 (APOL1) risk variants contribute to this greater risk, transplant nephrologists are increasingly using APOL1 testing to evaluate LD candidates of African ancestry. However, nephrologists do not consistently perform genetic counseling with LD candidates about APOL1 due to a lack of knowledge and skill in counseling about APOL1. Without proper counseling, APOL1 testing will magnify LD candidates' decisional conflict about donating, jeopardizing their informed consent. Given their elevated risk of ESRD post-donation, and AAs' widely-held cultural concerns about genetic testing, it is ethically critical to protect AA LD candidates' safety through APOL1 testing in a culturally competent manner to improve informed decisions about donating.

No transplant programs have integrated APOL1 testing into LD evaluation in a culturally competent manner. Clinical "chatbots," mobile apps that use artificial intelligence to provide genetic information to patients and relieve constraints on clinicians' time, can improve informed treatment decisions and reduce decisional conflict. The chatbot "Gia," created by a medical genetics company, can be adapted to any condition. However, no chatbot on APOL1 is currently available. No counseling training programs are available for nephrologists to counsel AA LDs about APOL1 and donation in a culturally competent manner. Given the shortage of genetic counselors, increasing nephrologists' genetic literacy is critical to integrating genetic testing into practice.

The objective of this study is to culturally adapt and evaluate the effectiveness of an APOL1 testing program for AA LDs at two transplant centers serving large AA LD populations (Chicago, IL, and Washington, DC). The APOL1 testing program will evaluate the effect of the culturally competent testing, chatbot, and counseling on AA LD candidates' decisional conflict about donating, preparedness for decision-making, willingness to donate, and satisfaction with informed consent. The specific aims are to:

1. Adapt Gia and transplant counseling to APOL1 for use in routine clinical practice
2. Evaluate the effectiveness of this intervention on decisional conflict, preparedness, and willingness to donate in a pre-post design
3. Evaluate the implementation of this intervention into clinical practice by using the RE-AIM framework to longitudinally evaluate nephrologist counseling practices and LDs' satisfaction with informed consent.

The impact of this study will be the creation of a model for APOL1 testing of AA LDs, which can then be implemented nationally via implementation science approaches. APOL1 will serve as a model for integrating culturally competent genetic testing into transplant and other practices to improve patient informed consent.

Detailed description: This project, "Integrating a culturally competent APOL1 genetic testing program into living donor evaluation," will integrate APOL1 testing into the evaluation of living kidney donor candidates of African ancestry. The study aims to reduce decisional conflict, improve preparedness for decision making, and increase satisfaction with informed consent for living donation for donor candidates at elevated risk of post-donation kidney failure. The APOL1 testing program will entail adapting established artificial intelligence conversational agents or "chatbots" to provide APOL1-specific information in preparation for donor candidates to undergo APOL1 testing, and adapting established genetic counseling discussions for transplant nephrologists to counsel donor candidates about APOL1 test results and engage in shared decision making to improve donor candidates' informed consent for living donation. APOL1 test results will be integrated into the electronic health record to provide clinical decision support to transplant nephrologists. The study will involve community engagement to ensure that testing and counseling is delivered in a culturally competent manner.

Using a hybrid effectiveness-implementation design, this study will simultaneously evaluate the effectiveness and implementation of the APOL1 testing program to more efficiently translate evidence into practice, as service delivery system factors for adoption and scale up are considered while effectiveness is tested. The study will be conducted at two geographically distinct transplant programs: Northwestern University in Chicago, IL, and Georgetown University in Washington, DC.

Participants include live kidney donor candidates of African ancestry undergoing donor evaluation. The investigators will recruit potential participants consecutively; with participants recruited in year 1 serving as the control group, and participants recruited in years 2-5 serving as the intervention group. Participants will be eligible for participation if they respond positively to one of three questions assessing African ancestry. Participants in the intervention group will use the chatbot for 5-7 minutes. Immediately thereafter, research staff will ask for participants' informed consent to undergo APOL1 genetic testing; those who agree will provide a saliva sample for testing. APOL1 test results will be integrated into the respective transplant program's electronic health records. Thereafter, transplant nephrologists will engage in a counseling discussion with donor candidates about APOL1 and living donation.

Distributional assumptions will be assessed to evaluate appropriateness of model specifications. For primary analyses, the mixed model framework will allow for incorporation of a random center effect to separate within- and between-center variance estimates. As participants will not be randomized to intervention arms, the proposed statistical analysis plan will also incorporate a multivariable modeling approach, with inclusion of potential confounders, to reduce bias in intervention effect estimates. Effect estimates will be reported with confidence intervals to convey variability in estimates.

Methods for sample size estimates were based on a simplified comparisons of means between the two arms (pre-post implementation periods). Necessary sample sizes were then inflated to account for multivariable model and to account for loss-to-follow-up, to ensure adequate power. The proposed sample size of 74 participants in the control period and 316 in the intervention period will provide at least 80-90% power to detect meaningful differences in mean Decisional Conflict Scale (DCS) score ranging from 5.0 to 7.7 units.

The impact of this study will be the creation of a model for integrating genetic testing into clinical practice that shows how to scale up genetic counseling services through the use of chatbots to deliver foundational information, and training nephrologists to deliver components of genetic counseling. Specifically, this model will demonstrate how to deliver APOL1 testing of live donor candidates, which can then be implemented across the country via implementation science approaches. The proposed study will prepare transplant programs to deliver culturally competent counseling coterminous with the completion of the NIH APOLLO study in \~5 years. The findings generated from this research have the potential to protect donor candidates' safety by improving their informed consent. As such, this proposal is timely and responsive to the NIDDK Program Announcement (PA-18-330) "Investigator-Initiated Clinical Trials Targeting Diseases within the Mission of NIDDK."

Eligibility criteria: Inclusion Criteria:

* Living kidney donor candidates who identify as African American/Black, Jamaican, Barbadian, Grenadian, Brazilian from Salvador Trinidadian, Panamanian, Honduran, Haitian, Garifunan, Palenque, Guyanese, Dominican, Peruvian, Belizean, and Native American, or state that they have African ancestry or are aware of having biologically-related family with African ancestry
* Living kidney donor candidates may be directed or non-directed donors
* Adults (ages 18+)
* English-speaking
* Cognitively intact individuals
* All genders

Exclusion Criteria:

* Individuals who do not identify as African American/Black and are not aware of having any biologically-related family with African ancestry and do not have African ancestry
* Only African Americans and people of African ancestry will be included because APOL1 risk variants are predominantly found in African Americans and people who have African ancestry.
* Pregnant women cannot be living kidney donors

Primary outcomes:
measure: Decisional Conflict Scale (DCS)
timeFrame: Day 1
measure: Decisional Conflict Scale (DCS)
timeFrame: Approximately Day 7
measure: Decisional Conflict Scale (DCS)
timeFrame: Approximately Day 30
measure: Decisional Conflict Scale (DCS)
timeFrame: Approximately Day 60
Secondary outcomes:
measure: Preparation for Decision Making Scale (PDMS) Scores range from: Higher scores reflect greater preparation for decision making (a better outcome)
timeFrame: Day 1
measure: Preparation for Decision Making Scale (PDMS) Scores range from: Higher scores reflect greater preparation for decision making (a better outcome)
timeFrame: Approximately Day 7
measure: Preparation for Decision Making Scale (PDMS) Scores range from: Higher scores reflect greater preparation for decision making (a better outcome)
timeFrame: Approximately Day 30
measure: Preparation for Decision Making Scale (PDMS) Scores range from: Higher scores reflect greater preparation for decision making (a better outcome)
timeFrame: Approximately Day 60
measure: Willingness to Donate Scores range from: 0 to 10. Higher scores reflect greater willingness to donate.
timeFrame: Approximately Day 1
measure: Willingness to Donate Scores range from: 0 to 10. Higher scores reflect greater willingness to donate.
timeFrame: Approximately Day 7
measure: Willingness to Donate Scores range from: 0 to 10. Higher scores reflect greater willingness to donate.
timeFrame: Approximately Day 30
measure: Willingness to Donate Scores range from: 0 to 10. Higher scores reflect greater willingness to donate.
timeFrame: Approximately Day 60
measure: Satisfaction with the Informed Consent Process
timeFrame: Approximately Day 7
measure: Satisfaction with the Informed Consent Process
timeFrame: Approximately Day 30
measure: Satisfaction with the Informed Consent Process
timeFrame: Approximately Day 60
Other outcomes:
Locations:
city: Washington
country: United States
facility: Medstar Georgetown Transplant Institute
state: District of Columbia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
Study officials:
affiliation: Northwestern University
name: Elisa J Gordon
role: PRINCIPAL_INVESTIGATOR
References: