COVID-19 Prevention and Mitigation Decision-Making Processes While Navigating Chronic Disease Care: Perspectives of Black Adults with Heart Failure and Diabetes.

BACKGROUND: Heart failure and diabetes are comorbidities that disproportionately contribute to high morbidity and mortality among Blacks. Further compounding the racial and ethnic disparities in COVID-19 health outcomes, Blacks with cardiometabolic diseases are at high risk of experiencing serious complications or mortality from COVID-19. This study aimed to assess how Blacks with heart failure and diabetes navigated chronic care management during the COVID-19 pandemic. METHODS: A mixed methods study including in-depth interviews and surveys with adults diagnosed with heart failure and diabetes (n = 17) was conducted in 2021-2022. Verbatim transcripts were analyzed using a thematic analysis approach. RESULTS: Participants reported that while the pandemic initially caused delays in access to health services, shifts to telemedicine allowed for continued care despite preferences for in-person appointments. Various sources of information were used in different ways to make decisions on how to best reduce health risks due to COVID-19, but individuals and institutions affiliated with science and medicine, or who promoted information from these sources, were considered to be the most trusted sources of information among those who relied on outside guidance when making health-related decisions. Individuals' self-awareness of their own high-risk status and perceived control over their exposure levels to the virus informed what COVID-19 prevention and mitigation strategies people used. CONCLUSION: Information backed by scientific data was an important health communication tool that alongside other factors, such as fear of mortality due to COVID-19, encouraged individuals to get vaccinated and adopt other COVID-19 prevention and mitigation behaviors.

Social determinants of health and diabetes: using a nationally representative sample to determine which social determinant of health model best predicts diabetes risk.

OBJECTIVES: Social determinants of health (SDOH) research demonstrates poverty, access to healthcare, discrimination, and environmental factors influence health outcomes. Several models are commonly used to assess SDOH, yet there is limited understanding of how these models differ regarding their ability to predict the influence of social determinants on diabetes risk. This study compares the utility of four SDOH models for predicting diabetes disparities. STUDY DESIGN: We utilized The National Longitudinal Study of Adolescent to Adulthood (Add Health) to compare SDOH models and their ability to predict risk of diabetes and obesity. METHODS: Previous literature has identified the World Health Organization (WHO), Healthy People, County Health Rankings, and Kaiser Family Foundation as the conventional SDOH models. We used these models to operationalize SDOH using the Add Health dataset. Add Health data were used to perform logistic regressions for HbA1c and linear regressions for body mass index (BMI). RESULTS: The Kaiser model accounted for the largest proportion of variance (19%) in BMI. Race/ethnicity was a consistent factor predicting BMI across models. Regarding HbA1c, the Kaiser model also accounted for the largest proportion of variance (17%). Race/ethnicity and wealth was a consistent factor predicting HbA1c across models. CONCLUSION: Policy and practice interventions should consider these factors when screening for and addressing the effects of SDOH on diabetes risk. Specific SDOH models can be constructed for diabetes based on which determinants have the largest predictive value.

Understanding Barriers and Facilitators to Integrated HIV and Hypertension Care in South Africa.

Background The burden of hypertension among people with HIV is high, particularly in low-and middle-income countries, yet gaps in hypertension screening and care in these settings persist. The objective of this study was to identify facilitators of and barriers to hypertension screening, treatment, and management among people with HIV seeking treatment in primary care clinics in Johannesburg, South Africa. Methods Using a cross-sectional study design, data were collected via interviews (n = 53) with people with HIV and hypertension and clinic managers and focus group discussions (n = 9) with clinic staff. A qualitative framework analysis approach guided by the Theoretical Domains Framework was used to identify and compare determinants of hypertension care across different stakeholder groups. Results Data from clinic staff and managers generated three themes characterizing facilitators of and barriers to the adoption and implementation of hypertension screening and treatment: 1) clinics have limited structural and operational capacity to support the implementation of integrated care models, 2) education and training on chronic care guidelines is inconsistent and often lacking across clinics, and 3) clinicians have the goal of enhancing chronic care within their clinics but first need to advocate for health system characteristics that will sustainably support integrated care. Patient data generated three themes characterizing existing facilitators of and barriers to clinic attendance and chronic disease self-management: 1) the threat of hypertension-related morbidity and mortality as a motivator for lifestyle change, 2) the emotional toll of clinic's logistical, staff, and resource challenges, and 3) hypertension self-management as a patchwork of informational and support sources. The main barriers to hypertension screening, treatment, and management were related to environmental resources and context (i.e., lack of enabling resources and siloed flow of clinic operations) the patients' knowledge and emotions (i.e., lack of awareness about hypertension risk, fear, and frustration). Clinical actors and patients differed in perceived need to prioritize HIV versus hypertension care. Conclusions The convergence of multi-stakeholder data regarding barriers to hypertension screening, treatment, and management highlight key areas for improvement, where tailored implementation strategies may address challenges recognized by each stakeholder group.

Association of collaborative care intervention features with depression and metabolic outcomes in the INDEPENDENT study: A mixed methods study.

AIMS: The INtegrating DEPrEssioN and Diabetes treatmENT (INDEPENDENT) trial tested a collaborative care model including electronic clinical decision support (CDS) for treating diabetes and depression in India. We aimed to assess which features of this clinically and cost-effective intervention were associated with improvements in diabetes and depression measures. METHODS: Post-hoc analysis of the INDEPENDENT trial data (189 intervention participants) was conducted to determine each intervention feature's effect: 1. Collaborative case reviews between expert psychiatrists and the care team; 2. Patient care-coordinator contacts; and 3. Clinicians' CDS prompt modifications. Primary outcome was baseline-to-12-months improvements in diabetes control, blood pressure, cholesterol, and depression. Implementer interviews revealed barriers and facilitators of intervention success. Joint displays integrated mixed methods' results. RESULTS: High baseline HbA1c≥ 74.9 mmol/mol (9%) was associated with 5.72 fewer care-coordinator contacts than those with better baseline HbA1c (76.8 mmol/mol, 9.18%, p < 0.001). Prompt modification proportions varied from 38.3% (diabetes) to 1.3% (LDL). Interviews found that providers' and participants' visit frequencies were preference dependent. Qualitative data elucidated patient-level factors that influenced number of clinical contacts and prompt modifications explaining their lack of association with clinical outcomes. CONCLUSION: Our mixed methods approach underlines the importance of the complementarity of different intervention features. Qualitative findings further illuminate reasons for variations in fidelity from the core model.

"I was having an internal conflict with myself." COVID-19 vaccination decision-making processes among pregnant women.

BACKGROUND: Vaccination serves as an efficient primary means of control for infectious diseases. However, in the case of the COVID-19 pandemic, pregnant women within the United States had the lowest rates of COVID-19 vaccination and reported the lowest intent to vaccinate. OBJECTIVES: To explore the decision-making process for COVID-19 vaccination for people pregnant during the pandemic. DESIGN: A secondary analysis of data from a mixed-methods study that examined the impact of COVID-19 on experiences of prenatal care, birth support, and delivery in the Southern United States. METHODS: This study used a descriptive phenomenological approach to thematically analyze in-depth interviews (n = 20) with adult women who were pregnant by January 2020 and had their prenatal care and delivery during the pandemic beginning in March 2020. The transcripts were de-identified, coded, and thematically analyzed to saturation to identify drivers of COVID-19 vaccine decision-making based on COVID-19 vaccination status and timing. Comparative analyses were conducted to assess differences in decision-making processes based on race/ethnicity and parity. Participants also completed a sociodemographic survey that included their COVID-19 vaccination status. RESULTS: Two themes emerged, the weighing of parallel risks and priorities from different sources resulting in vaccine decisional conflict and the need to reconcile that conflict via multiple strategies. All participants weighed priorities and risks from multiple areas of their lives and described internal conflict around vaccination. Participants described tailoring decisions to household dynamics, reconciling public and private values around vaccination, and the impact of their identities on the decision-making process. While many described concerns over vaccine safety and fetal health, uniquely, many highlighted weighing the impact of prior pregnancy loss history, with some choosing other preventive measures like social distancing or mask-wearing, which they deemed less risky. CONCLUSION: Pregnant people make complex COVID-19 vaccination decisions, which must be considered in future vaccine messaging and advocacy for this group.

Gender Attributions by Cisgender and Gender Diverse Listeners Rating Vowels, Reading, and Monologues.

OBJECTIVES: To determine if listeners' attributions of speakers' gender vary by linguistic context and/or the listeners' gender identity. METHODS: Seventeen self-identified transgender adults assigned male at birth were audio-recorded prolonging /a/, reading sentences, and saying spontaneous monologues. Eighteen adults (10 cisgender and 8 gender-diverse individuals) listened and used a 1-5 scale (1: very masculine, 2: somewhat masculine, 3: androgynous, 4: somewhat feminine, and 5: very feminine) to rate the gender attribution of each speech sample. RESULTS: The intra-rater reliability was moderate to excellent (0.62-1.00). Ratings by cisgender and gender-diverse listeners were not significantly different. Ratings were not significantly different between different speech contexts of vowel, reading, and spontaneous monologue speech samples. CONCLUSIONS: Transwomen have many variables available to consider and use in their communication. The linguistic context (eg, reading a speech versus spontaneous monologue) or listener's gender does not appear to be highly influential factors in how listeners attribute gender.

Attitudes and beliefs about sleep health among a racially and ethnically diverse sample of overweight/obese adults.

OBJECTIVES: To identify and compare how sleep-related attitudes and beliefs vary among racially and ethnically diverse adults with risk factors for cardio-metabolic disease. METHODS: This exploratory qualitative study used online focus group discussions (N = 4 groups among 17 individuals) to collect information about sleep attitudes, beliefs, and practices following participation in the Mindfulness Intervention to Improve Sleep and Reduce Diabetes Risk Among a Diverse Sample in Atlanta (MINDS) study. A rapid analyses approach was used to identify shared themes related to attitudes and beliefs about sleep health and sleep practices across participants. RESULTS: Participants on average were 31years old, 88% female, and identified as Black/African American (52.9%), White (17.7%), Asian (11.8%), and Hispanic (17.7%). Three themes related to attitudes and beliefs about sleep health were identified: prioritization of sleep to improve one's overall health, re-evaluating sleep needs, and interpersonal barriers to sleep. For Black/African American participants prioritizing sleep was coupled with a want to minimize stress as a long-term health promotion strategy, whereas individuals of other races/ethnicities were more focused on the immediate benefits of getting sufficient sleep. Individuals had reappraised their sleep needs and worked to improve their sleep hygiene accordingly, yet still experienced barriers to sleep. The most common barrier to sleep was sharing a sleep environment with someone who had conflicting sleep routines and practices. CONCLUSION: The results of this study suggest perceived benefits of and barriers to sleep vary by race/ethnicity, thus future interventions should be culturally tailored to enhance effectiveness.

Emerging Ideas. A ripple effect: Does I-sharing with a stranger promote compromise in cohabiting couples?

Background: Living together harmoniously requires compromise. Research on the psychological factors that promote compromise frequently focuses on individual differences and interpersonal environment. The current research takes a different approach by asking what role I-sharing (i.e., the feeling that others share the same in-the-moment, subjective experience as oneself) plays in the success of a cohabiting couple's compromise efforts. Objective: Drawing from work on the prosocial outcomes associated with I-sharing, we asked whether I-sharing with a stranger enhances couples' ability to compromise. Method: Both members of a cohabiting couple privately reported the percentage of time they spend on household tasks (the Division of Household Labor inventory [DHL]) before undergoing a manipulation in which they either did or did not have an I-sharing experience with a stranger. Participants then completed the DHL again, this time working together with their cohabiting partner to reach a consensus in their responses. Finally, participants had another chance to complete the DHL in private, receiving the instruction to respond with their true beliefs. Results: When relationship partners worked together to complete the DHL at the second reporting, their responses were identical. At the third (private) DHL reporting, consistent with prediction, couples assigned to the I-share condition showed more agreement with their partner than couples assigned to the No I-share condition. Conclusion: This finding suggests that the prosociality generated by I-sharing can promote compromise in cohabiting couples. Implications: I-sharing holds promise as a therapeutic tool to promote compromise in treatment-seeking families and couples.

Exploring the Social Determinants of Health and Health Disparities in Traumatic Brain Injury: A Scoping Review.

Traumatic brain injury (TBI) is a global health concern, that can leave lasting physical, cognitive, and/or behavioral changes for many who sustain this type of injury. Because of the heterogeneity of this population, development of appropriate intervention tools can be difficult. Social determinants of health (SDoH) are factors that may impact TBI incidence, recovery, and outcome. The purpose of this study is to describe and analyze the existing literature regarding the prevailing SDoH and health disparities (HDs) associated with TBI in adults. A scoping review, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework was used to explore three electronic databases-PubMed, Medline, and CINAHL. Searches identified peer-reviewed empirical literature addressing aspects of SDoH and HDs related to TBI. A total of 123 records were identified and reduced to 27 studies based on inclusion criteria. Results revealed race/ethnicity was the most commonly reported SDoH impacting TBI, followed by an individual's insurance status. Health disparities were noted to occur across the continuum of TBI, including TBI risk, acute hospitalization, rehabilitation, and recovery. The most frequently reported HD was that Whites are more likely to be discharged to inpatient rehabilitation compared to racial/ethnic minorities. Health disparities associated with TBI are most commonly associated with the race/ethnicity SDoH, though insurance status and socioeconomic status commonly influence health inequities as well. The additional need for evidence related to the impact of other, lesser researched, SDoH is discussed, as well as clinical implications that can be used to target intervention for at-risk groups using an individual's known SDoH.

LMIC Research Centers' Experiences Hosting U.S. and LMIC Trainees: Evaluation of the Fogarty Global Health Fellows and Scholars Program, 2012 to 2020.

In this mixed-methods study, we explore themes that emerged from a survey assessing the programmatic experiences of mentors and administrators at institutions in low- and middle-income countries (LMICs) hosting trainees supported by the Fogarty International Center's Global Health Program for Fellows and Scholars. A total of 89 of 170 potential respondents representing 31 countries completed the survey (response rate, 52.4%). There was agreement among respondents that their institutions received sufficient funds to support trainees and had the capacity to manage operational and financial aspects of the program. A majority also agreed that both LMIC and U.S. trainees were beneficial to the host institutions, and that trainee projects were relevant to the needs of the host country. Respondents felt that program benefits to LMIC trainees could be improved by increasing the research consumables budget, increasing the flexibility of program timelines, and increasing engagement between LMIC and U.S. trainees and institutions. Respondents indicated that both U.S. and LMIC trainees behaved professionally (including demonstrating respectful and ethical behavior) and took appropriate initiative to conduct their research projects. Findings from this study will help inform innovations to similar training initiatives that will enhance sustainability and improve program performance, and will be responsive to local needs.

Patient-Centered Approaches to Cognitive Assessment in Acute TBI.

PURPOSE OF THE REVIEW: The purpose of this article is to help clinicians understand how underlying pathophysiologies and medical comorbidities associated with acute traumatic brain injury (TBI) can impact assessment of cognition during the initial stages of recovery. Clinicians can use information from this article to develop assessment plans rooted in patient-centered care. RECENT FINDINGS: The authors conducted a review of the literature related to the assessment of cognition in acute TBI, focusing on pathophysiology, medical comorbidities, and assessment approaches. Results indicated that TBI pathophysiologies associated with white and gray matter changes make many patients vulnerable to cognitive deficits. Acute comorbidities such as psychological and pain status influence cognitive abilities as well. The current approaches to cognitive assessment can be limited in many ways, though by using the patient's neuropathological profile, noted comorbidities, and other patient specific factors, clinicians can potentially improve the effectiveness of assessment.

Feasibility, appropriateness, and acceptability of a mobile mindfulness meditation intervention to improve sleep quality among a racially/ethnically diverse population.

OBJECTIVES: To evaluate the acceptability, appropriateness, and feasibility of using a mindfulness meditation mobile application to improve sleep quality among a diverse group of adults. METHODS: This explanatory qualitative study used online focus group discussions (N = 4 groups with 17 individuals) to collect information about user experiences with a mindfulness meditation mobile application (Headspace) among participants enrolled in the MINDS study. A rapid analyses approach was used to descriptively compare motivators of app use, barriers and facilitators to app use, and perceived tailoring needs across participants. RESULTS: Participants on average were 30 years old, 88% female, and identified as Black/African American (52.9%), White (29.4%), Asian (11.8%), and Hispanic (17.6%). All participants felt the app was acceptable and appreciated the ability to personalize their app experience. Individuals with ≥50% intervention adherence (daily use for 30 days) reported being motivated to use the app because it helped them to fall asleep faster, while the remainder of participants used the app to relax throughout the day and faced external barriers to app use (eg, lack of time) and difficulty with app navigation. Only those participants who used the app exclusively in the evenings reported falling asleep faster and staying asleep. Suggestions for tailoring the app differed by race and age. Only Black/African American participants preferred using an instructor based on their race and gender. CONCLUSION: Using a mobile meditation app to enhance sleep quality is acceptable and feasible, but additional tailoring for Black/African American individuals may improve uptake in this population.

A realist process evaluation of the INtegrating DEPrEssioN and Diabetes treatmENT (INDEPENDENT) randomized controlled trial in India.

Aims: We aimed to determine what key resources, mechanisms, and contextual factors are necessary to integrate depression and diabetes treatment into low-resource settings. Methods: A realist evaluation framework was employed to conduct a comparative case study. Data were collected through document review, key informant interviews (n = 4), activity logs, and interviews with implementing health care providers (n = 11) to test and refine program theories for collaborative care. Results: Efforts to enhance patient care coordination (i.e., adapting clinics' patient flow and resources, on-going trainings, and on-site support for care coordinators) improved implementation of depression treatment by usual care diabetes physicians. Clinician's avoidance of the term depression was identified as a barrier to mental health counseling and treatment. Conclusions: The variations in organizational features and processes linked to implementation activities across two clinics provided an opportunity to examine how and why different contextual factors help or hinder the implementation process. Findings from this study demonstrate that successful implementation of an integrated depression and diabetes care model is feasible in a low-resource setting, while the revised program theories provide an explanatory framework of coordinated care implementation processes that can inform future efforts to disseminate and scale this care model.

Collaborative Quality Improvement Strategy in Secondary Prevention of Cardiovascular Disease in India: Findings from a Multi-Stakeholder, Qualitative Study using Consolidated Framework for Implementation Research (CFIR).

Background: Cardiovascular disease (CVD) is highly prevalent in India, and little is known about the perception of patients and providers about a package of collaborative quality improvement (C-QIP) strategies consisting of provider-focused electronic health records-decision support system (EHR-DSS), non-physician health workers (NPHW), and patient-facing text messages to enhance the CVD care. Objective: To explore the barriers and enablers of the C-QIP strategy from the perspective of providers, health administrators, patients, and care givers in India. Methods: We conducted a qualitative study using the consolidated framework for implementation research (CFIR) to understand the challenges and facilitators of implementing C-QIP strategy to enhance CVD care in the Indian context. A diverse sample of 38 physicians, 14 non-physician health workers (nurses, pharmacists), 4 health administrators, and 16 patients and their caregivers participated in semi-structured interviews. All interviews were audio-recorded, transcribed, translated, anonymised, and coded using MAXQDA software. We used the framework method and CFIR domains to analyze the qualitative data. Results: Barriers perceived from providers' and health administrators' perspectives in providing quality CVD care were high patient volume, physician burnout, lack of robust communication or referral system, paucity of electronic health records, lack of patient counsellors, polypharmacy, poor patient adherence to medications, and lack of financial incentives. Low health literacy, high cost of treatment, misinformation bias, and difficulty in maintaining lifestyle changes were barriers from patients' perspectives. The CFIR identified key enablers for the implementation of C-QIP such as standardized treatment protocol, reduced medication errors, improved physician-patient relationships, and enhanced patient self-care through trained and supported NPHW. Barriers included: heterogenous healthcare settings, diverse patient groups and comorbidities, associated costs of care and interoperability, confidentiality, and data privacy issues around the use of EHR-DSS. Conclusion: Strategies to enhance CVD care must be low-cost, culturally acceptable, and integrated into existing care pathways.

Effects of a lifestyle intervention on depression and anxiety among adults at risk for diabetes in India: A secondary analysis of the Kerala Diabetes Prevention Program.

The impact of lifestyle interventions on diabetes and mental health conditions have been documented among people with diabetes. However, the mental health benefits of lifestyle interventions designed for diabetes prevention have not been systematically investigated among people at high risk of diabetes, particularly in low- and middle-income countries. We examined the effects of a 12-month peer support lifestyle intervention designed for diabetes prevention on depression and anxiety symptomology in the sample population of the Kerala Diabetes Prevention Program. Mixed-effects linear regression models were used to examine the effect of the intervention on depression and anxiety scores at 12 and 24 months in the total sample of 1007 adults at risk for diabetes and among those with mild-severe depressive or anxiety symptoms at baseline (n = 326 for depression; n = 203 for anxiety). Among all participants, the intervention group had a significantly higher reduction of depressive symptoms as compared to the control group at 12 months (mean diff score = -0.51; 95% CI: -0.95, -0.07; P = 0.02). This effect was not sustained at 24 months. There were no significant intervention effects for anxiety. Among those with mild-severe symptoms at baseline, the intervention group had a significantly higher reduction of depressive symptoms (mean diff score = -1.55; 95% CI -2.50, -0.6; P = 0.001) and anxiety symptoms (mean diff score = -1.64; 95% CI -2.76, -0.52; P = 0.004) at 12 months. The effect was sustained at 24 months for depression, but not anxiety. Lifestyle interventions designed for prevention of diabetes might improve depressive and anxiety symptoms in the short-term, particularly among those with mild-severe symptoms.

A Scoping Review of Cognitive Assessment in Adults With Acute Traumatic Brain Injury.

PURPOSE: The purpose of this study was to describe and synthesize the current research regarding the prevailing cognitive domains impacted by acute traumatic brain injury (TBI) in adults. Standardized and nonstandardized assessments of cognitive function and comorbidities influencing cognitive function during the initial stages of recovery are presented to help guide clinical assessment. METHOD: A scoping review, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework, was used to explore four electronic databases. Searches identified peer-reviewed empirical literature addressing aspects of cognitive domains impacted after TBI, cognitive assessment, and comorbidities impacting assessment in adults after acute TBI. RESULTS: A total of 1,072 records were identified and reduced to 75 studies based on inclusion criteria. The cognitive domains most impacted in acute TBI were memory and executive function. The Glasgow Coma Scale (GCS) was the most frequently used tool to assess cognitive abilities, despite it being a measurement of consciousness, not of cognition. Psychological changes were the most commonly noted comorbidity impacting cognitive assessment. CONCLUSIONS: Assessment of cognition after acute TBI requires a multifaceted approach that considers the typical profile of cognitive impairment, as well as patient-specific factors influencing cognitive abilities following initial brain injury. The present results support the generally held view that memory and executive function deficits are common cognitive difficulties associated with acute TBI in adults. The GCS remains the most widely used tool to assess function, though numerous tools are available that specifically address cognitive domains. Acute medical comorbidities common within this stage of injury are highlighted, as well as gaps of clinical knowledge that remain. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.18372086.

Effect of a collaborative care model on anxiety symptoms among patients with depression and diabetes in India: The INDEPENDENT randomized clinical trial.

OBJECTIVE: We assessed the impact of a collaborative care intervention on anxiety symptoms among participants in India with comorbid depression, poorly controlled diabetes, and moderate to severe anxiety symptoms. METHOD: We analyzed data from a randomized controlled trial conducted at four diabetes clinics in India. Participants received either collaborative care or usual care. We included only participants who scored ⩾10 on the Generalized Anxiety Disorder-7 (GAD-7) at baseline. We estimated the effect of the intervention on clinically significant reduction in anxiety symptoms; we considered several potential baseline moderators and mediation by anti-depressant use. RESULTS: One hundred and seventy-two participants scored 10 or above on the GAD-7 at baseline. Collaborative care participants were more likely than control participants to achieve a clinically significant reduction in anxiety symptoms at 6 and 12 months (65.7% vs. 41.4% at 12 months, p = 0.002); these differences were not sustained at 18 or 24 months. There was little evidence of moderation by participant characteristics at baseline, and effects were not mediated by anti-depressant use. CONCLUSIONS: Collaborative care for the treatment of depression and type 2 diabetes can lead to clinically significant reductions in anxiety symptoms among patients with anxiety. Effects were notable during the active intervention period but not over the year post-intervention.

Safety and Efficacy of GFB-887, a TRPC5 Channel Inhibitor, in Patients With Focal Segmental Glomerulosclerosis, Treatment-Resistant Minimal Change Disease, or Diabetic Nephropathy: TRACTION-2 Trial Design.

INTRODUCTION: A critical unmet need exists for precision therapies for chronic kidney disease. GFB-887 is a podocyte-targeting, small molecule inhibitor of transient receptor potential canonical-5 (TRPC5) designed specifically to treat patients with glomerular kidney diseases characterized by an overactivation of the TRPC5-Rac1 pathway. In a first-in-human study, GFB-887 was found to be safe and well tolerated, had a pharmacokinetic (PK) profile allowing once-daily dosing, and dose dependently decreased urinary Rac1 in healthy adults. METHODS: TRACTION-2 is a phase 2a, double-blind, placebo-controlled, multiple-ascending dose study of GFB-887 in patients with focal segmental glomerulosclerosis (FSGS), treatment-resistant minimal change disease (TR-MCD), or diabetic nephropathy (DN) (NCT04387448). Adult patients on stable renin-angiotensin system blockade and/or immunosuppression with persistent proteinuria will be randomized and dosed in 3 ascending dose levels to GFB-887 or placebo for 12 weeks. Cohorts may be expanded or biomarker-enriched depending upon results of an adaptive interim analysis. RESULTS: The primary objective is to evaluate the effect of increasing doses of GFB-887 on proteinuria. Safety and tolerability, quality of life, pharmacokinetic/pharmacodynamic profiles, and the potential association of urinary Rac1 with efficacy will also be evaluated. The projected sample size has 80% power to detect a treatment difference in proteinuria of 54% (FSGS/TR-MCD) or 44% (DN) compared to placebo. CONCLUSION: TRACTION-2 will explore whether targeted blockade of the TRPC5-Rac1 pathway with GFB-887 is an efficacious and safe treatment strategy for patients with FSGS, TR-MCD, and DN and the potential value of urinary Rac1 as a predictive biomarker of treatment response.