ABSTRACT IMPACT: My work evaluates the impact of electronic data capture/eSource on several aspects of clinical trial efficiency and scale, aiming to demonstrate how eSource can be used to improve the way we run clinical trials. OBJECTIVES/GOALS: Using eSource may increase the efficiency of data collection in clinical trials. However, adoption of eSource has been slow. We reviewed over 100 large multinational clinical trials to analyze how eSource use correlated with trial size, sponsor collaborations, time to complete, and time to publication. METHODS/STUDY POPULATION: We searched ClinicalTrials.gov for completed, interventional, Stage II-IV clinical trials with posted results and an uploaded study protocol document. This produced 3,962 trials. We identified all studies with over 1,200 participants and sites in multiple countries (or at least 100 sites in one country). After eliminating ten studies with duplicate protocols, we had a database of 123 trials. From the ClinicalTrials.gov listing, the study protocol, and any published papers, we determined the start, end, and publication dates, data collection protocol, sponsors and collaborators, and any reasons given for delays for each trial. We performed statistical tests comparing trial delay, participant and country count, and collaboration status (yes or no) between the two groups (eSource users and non-eSource users). RESULTS/ANTICIPATED RESULTS: Of our 123 trials, 60 (48.7%) used eSource, 48 (39.1%) used paper source documentation, and 15 (12.2%) used some combination. We found no statistically significant difference between eSource and non-eSource trials in terms of trial delay (p=0.43), time to publish (p=0.33), collaboration status (p=0.54), number of participants (p=0.36), or number of countries (p=0.12). However, our analysis was limited by what data was publically available. To investigate the effects of eSource on site efficiency, data accuracy, and data security, which are three major factors behind the FDA’s 2013 eSource recommendation, we would need access to proprietary information from trial sponsors. DISCUSSION/SIGNIFICANCE OF FINDINGS: The use of eSource in large multinational clinical trials is not correlated with a change in time to completion or publication nor a higher number of participants or countries. We aim to acquire proprietary data to further analyze the impacts of eSource on trial efficiency, data accuracy, and data security.

Biospecimen repositories play a vital role in enabling investigation of biologic mechanisms, identification of disease-related biomarkers, advances in diagnostic assays, recognition of microbial evolution, and characterization of new therapeutic targets for intervention. They rely on the complex integration of scientific need, regulatory oversight, quality control in collection, processing and tracking, and linkage to robust phenotype information. The COVID-19 pandemic amplified many of these considerations and illuminated new challenges, all while academic health centers were trying to adapt to unprecedented clinical demands and heightened research constraints not witnessed in over 100 years. The outbreak demanded rapid understanding of SARS-CoV-2 to develop diagnostics and therapeutics, prompting the immediate need for access to high quality, well-characterized COVID-19-associated biospecimens. We surveyed 60 Clinical and Translational Science Award (CTSA) hubs to better understand the strategies and barriers encountered in biobanking before and in response to the COVID-19 pandemic. Feedback revealed a major shift in biorepository model, specimen-acquisition and consent process from a combination of investigator-initiated and institutional protocols to an enterprise-serving strategy. CTSA hubs were well equipped to leverage established capacities and expertise to quickly respond to the scientific needs of this crisis through support of institutional approaches in biorepository management.

ABSTRACT IMPACT: The findings suggest that targeting parenting stress in combination with psychoeducation on nutrition and physical activity may have positive effects in improving healthy food choices such as reduction of fast food intake, which may in turn impact the health of toddlers and their families. OBJECTIVES/GOALS: Parent stress is associated with a myriad of unhealthy behaviors including overeating, decreased physical activity, which contribute to increased weight. Several programs have aimed to increase education of nutrition, but few have focused on parent stress to improve healthy food intake. The present study assessed parent stress and fast food intake. METHODS/STUDY POPULATION: Parents who have obesity and had a toddler in the age group of 2-5 years were enrolled for a preventive intervention study to assess the effect of a parent-based intervention to improve family health choices and reduce childhood obesity risk. The sample included 105 participants, mean age 34.80 (6.27) years old, mean body mass index (BMI) 35.51 kg/m2, 39.0% Non-Hispanic White, 20.0% Non-Hispanic Black, 22.9% multiracial, 12.4% Hispanic, and 5.7% other. Stress was assessed using the Perceived Stress Scale (PSS) to assess overall general stress and the Parenting Stress Index (PSI) to assess parent-specific stress. Chaos in the home and fast food intake were also assessed using self-report surveys. RESULTS/ANTICIPATED RESULTS: Preliminary results are based on available data as of October 2020, data collection and recruitment are still in progress. There was a significant correlation between fast food intake with PSS (r=.18, p=.04), chaos (r=.24, p=.02), and PSI (r=.25, p=.01). Using a hierarchical regression model, we entered home chaos in the first block which explained a significant amount of the variability (R2= .06, p=.04). PSS was entered in the second block, which was not significant (R2 change=.01, p=.50), and in the final block PSI was entered and was significant (R2 change=.13, p <.01). DISCUSSION/SIGNIFICANCE OF FINDINGS: The data indicate that parenting stress uniquely predicts fast food intake above and beyond what could be explained by home chaos and general perceived stress. Future analyses will assess a parent-based intervention targeting stress reduction to improve weight and health for the parent and their toddlers in order to reduce childhood obesity risk.

Rapid development and deployment of diagnostic testing for COVID-19 have been a key component of the public health response to the pandemic. Out of necessity, academic and other clinical laboratories developed laboratory testing innovations for COVID-19 to meet clinical testing demands. In addition to constraints on local testing supplies and equipment, a rapidly changing regulatory framework created challenges for translational scientists. Illustrative examples of approaches used to develop laboratory tests during the early stages of the COVID-19 pandemic demonstrate effective team science approaches to this challenging clinical care and public health emergency. These experiences and the associated lessons learned are relevant to the development of public health response plans for future pandemics.

ABSTRACT IMPACT: Impaired neuromuscular control could lead to the failure in activation and deactivation of the target muscles in a timely manner, with the concurrence of activities of non-targeted muscles. OBJECTIVES/GOALS: Stroke leads to impaired capacity to manipulate objects with the hand in terms of timing and strength of grasp. The influence of abnormal coupling across more proximal arm muscles post stroke on the failure in normal functioning of finger flexor muscle activity is of interest to investigate. METHODS/STUDY POPULATION: We have recruited 12 participants with stroke hemiparesis in the sub-acute or chronic stage. Motor impairment of the arm was assessed using electromyography (EMG) and the Fugl-Meyer Upper Extremity (FMUE) assessment. Participants were requested to flex and relax the metacarpophalangeal (MCP) joints against motorized resistance in response to audible tones to determine timing and strength during flexion. They were asked to flex maximally, as quickly as possible, in response to the first of a pair of tones, and relax as quickly as possible after the second tone. Delays in initiation and termination were evaluated using EMG responses versus a predefined threshold. RESULTS/ANTICIPATED RESULTS: We anticipate greater delays in grasp initiation as well as in grasp termination in participants with a greater extent of abnormal coupling across more proximal muscles of the upper extremity in comparison to participants with a less extent, using the results of the FMUE assessment. Also it is expected that participants with a greater extent of the flexion synergy produce a less extent of force generation. The EMG results will show that activities of more proximal arm muscles precede the initiation of MCP flexion and their activity termination precedes that of MCP flexion, significantly more in participants with a greater extent of the flexion synergy. DISCUSSION/SIGNIFICANCE OF FINDINGS: The flexion synergy over the arm following stroke affects the timing and strength of hand grasp. Impaired neuromuscular control could lead to the failure in activation and deactivation of the target muscles in a timely manner, with the concurrence of activities of non-targeted muscles.

ABSTRACT IMPACT: This study helps translate investigational bedside optical coherence tomography into improved diagnosis and care of preterm infants at risk for retinopathy of prematurity. OBJECTIVES/GOALS: In retinopathy of prematurity screening, fundus photography may be of limited quality in eyes with dark fundus pigmentation (FP). The goal of this study was to evaluate the impact of FP on overall scan quality and retinal layer visibility on investigational bedside optical coherence tomography (OCT) in preterm infants. METHODS/STUDY POPULATION: We analyzed 846 OCT scans captured prospectively from 188 eyes of 94 preterm infants enrolled in the BabySTEPS study (NCT02887157). Trained ophthalmologists, masked to OCT findings, determined FP (blond, medium, or dark). Expert graders, masked to FP, evaluated OCT images for: 1) overall OCT quality (excellent, acceptable, poor, or unusable); and 2) all age-appropriate retinal layers visible (yes or no). To assess the association of FP with OCT quality (excellent/acceptable or poor/unusable) and retinal layer visibility, we performed multivariable logistic regression modeling, adjusting for biologic and demographic confounders and correlations from repeated OCT scans and paired eyes. RESULTS/ANTICIPATED RESULTS: Mean birthweight was 964 (SD=283) grams, mean gestational age was 27.8 (SD=2.6) weeks, 48 (51%) infants were male, and 51 (54%) were non-white. On exam, 72 (38%) eyes had blond FP, 92 (49%) had medium, and 24 (13%) had dark. OCT quality was excellent or acceptable in 725 scans (86%) and all age-appropriate retinal layers were visible in 781 scans (92%). Compared to eyes with blond FP, eyes with medium and dark FP did not have higher odds of poor/unusable OCT scan quality (adjusted OR 0.87 [95% CI 0.50-1.48] and 0.49 [95% CI 0.16-1.55], respectively) or not all age-appropriate retinal layers visible on OCT (adjusted OR 1.17 [95% CI 0.39-3.51] and 0.57 [95% CI 0.15-2.20], respectively). DISCUSSION/SIGNIFICANCE OF FINDINGS: Medium and dark FP did not impact overall scan quality or age-appropriate retinal layer visibility on investigational bedside OCT in preterm infants. This study supports the feasibility of using OCT to analyze retinal microanatomy in diverse populations of preterm infants with a range of FP.

Efforts to move community engagement in research from marginalized to mainstream include the NIH requiring community engagement programs in all Clinical and Translational Science Awards (CTSAs). However, the COVID-19 pandemic has exposed how little these efforts have changed the dominant culture of clinical research. When faced with the urgent need to generate knowledge about prevention and treatment of the novel coronavirus, researchers largely neglected to involve community stakeholders early in the research process. This failure cannot be divorced from the broader context of systemic racism in the US that has contributed to Black, Indigenous, and People of Color (BIPOC) communities bearing a disproportionate toll from COVID-19, being underrepresented in COVID-19 clinical trials, and expressing greater hesitancy about COVID-19 vaccination. We call on research funders and research institutions to take decisive action to make community engagement obligatory, not optional, in all clinical and translational research and to center BIPOC communities in this process. Recommended actions include funding agencies requiring all research proposals involving human participants to include a community engagement plan, providing adequate funding to support ongoing community engagement, including community stakeholders in agency governance and proposal reviews, promoting racial and ethnic diversity in the research workforce, and making a course in community engaged research a requirement for Masters of Clinical Research curricula.

ABSTRACT IMPACT: By restoring the gut microbiota in patients with acute myeloid leukemia exposed to antibiotics, we will reduce infections during and after curative-intent chemotherapy. OBJECTIVES/GOALS: Infection is a leading cause of death in acute myeloid leukemia (AML). Antibiotics disrupt the gut microbiota, promoting secondary infections. Through a double-blind randomized placebo-controlled phase 2 trial, we will determine whether microbiota restoration using fecal microbiota transplantation (FMT) prevents infections in AML patients. METHODS/STUDY POPULATION: 72 intensively treated AML patients at our institution are randomized in a 2:1 ratio to FMT (arm A) or placebo (arm B). After completing each course of antibacterial antibiotics, patients receive one study treatment. Up to 3 study treatments are administered over 3 months. FMT is delivered as a third-party oral product containing microbiota (˜5x10^11 bacteria) in 4-6 capsules. Stool samples are collected before and after each study treatment. The primary endpoint is 4-month overall infection rate. 16S rRNA gene sequencing of stool samples is used to determine specific taxa that are under- or over-represented in samples preceding infections and compare the two arms for key microbiome features including diversity and composition. Bloodstream infection within 7 days after FMT counts towards stopping rule. RESULTS/ANTICIPATED RESULTS: Five patients have been enrolled: 4 have received 1 dose and 1 received 2 doses. The only adverse event (possibly related to study treatment) has been grade 1 abdominal pain in 1 patient. Notably, no bloodstream infection has occurred. All planned samples have been collected and are sequenced in batches. We expect arm A patients to experience fewer infections and fewer intestinal blooms of pathobionts, and both arms to experience intestinal blooms before specific infections. An interim efficacy analysis will be performed at half total enrollment. DISCUSSION/SIGNIFICANCE OF FINDINGS: Current supportive care during intensive chemotherapy is fundamentally anti-microbial and results in dysbiosis, with detrimental consequences. We will establish the evidence for FMT as a restorative strategy in AML patients. This is the first randomized placebo-controlled trial of repeated FMT, with potential implications to other cancers.

The 2020 COVID-19 pandemic has had a profound impact on the clinical research enterprises at the 60 Clinical and Translational Science Award (CTSA) Hubs throughout the nation. There was simultaneously a need to expand research to obtain crucial data about disease prognosis and therapy and enormous limitations on conducting research as localities and institutions limited travel and person-to-person contact. These imperatives resulted in major changes in the way research was conducted, including expediting Institutional Review Board review, shifting to remote interactions with participants, centralizing decision-making in prioritizing research protocols, establishing biobanks, adopting novel informatics platforms, and distributing study drugs in unconventional ways. National CTSA Steering Committee meetings provided an opportunity to share best practices and develop the idea of capturing the CTSA program experiences in a series of papers. Here we bring together the recommendations from those papers in a list of specific actions that research sites can take to strengthen operations and prepare for similar future public health emergencies. Most importantly, creative innovations developed in response to the COVID-19 pandemic deserve serious consideration for adoption as new standards, thus converting the painful trauma of the pandemic into “post-traumatic growth” that makes the clinical research enterprise stronger, more resilient, and more effective.

ABSTRACT IMPACT: A short treatment of 8 obese postmenopausal women with conjugated estrogens and bazedoxifene does not alter insulin sensitivity or ectopic fat but increases serum markers of hepatic de novo lipogenesis and production of triacylglycerides. OBJECTIVES/GOALS: Combining conjugated estrogens (CE) with the selective estrogen receptor modulator bazedoxifene (BZA) is a novel, orally-administered menopausal therapy. We investigated the effect of CE/BZA on insulin sensitivity, energy metabolism, and serum metabolome in postmenopausal women with obesity. METHODS/STUDY POPULATION: We conducted a randomized, double-blind, crossover pilot trial, testing the effect of CE/BZA on cardiometabolic health in postmenopausal women. Eight postmenopausal women (age 50-60 y, BMI 30-40 kg/m2) were randomization to an 8-week CE/BZA or placebo treatment separated by an 8-week washout period [NCT02274571]. The primary outcome was insulin sensitivity (hyperinsulinemic-euglycemic clamp), while secondary outcomes included body composition (DXA); resting metabolic rate (RMR); substrate oxidation (indirect calorimetry); ectopic lipids (1H-MRS); fat cell size, adipose and skeletal muscle gene expression (biopsies); inflammatory markers; and serum metabolome (LC/MS). RESULTS/ANTICIPATED RESULTS: CE/BZA had no effect on insulin sensitivity, body composition, ectopic fat, or substrate oxidation, but resulted in a non-significant increase in RMR (basal: p=0.06; high-dose clamp: p=0.08) compared to placebo. CE/BZA increased serum high-density lipoprotein cholesterol. CE/BZA also increased serum diacylglycerol (DAG) and triacylglycerol (TAG) species containing long-chain saturated, mono- and polyunsaturated fatty acids (FAs), and decreased long-chain acylcarnitines. These findings possibly reflect increased hepatic de novo FA synthesis and esterification into TAGs, and decreased FA oxidation, respectively (p<0.05). CE/BZA increased serum phosphatidylcholines, phosphatidylethanolamines, ceramides, and sphingomyelins, possibly reflecting the increase in lipoproteins (p<0.05). DISCUSSION/SIGNIFICANCE OF FINDINGS: A short treatment of postmenopausal women with CE/BZA did not alter insulin action or ectopic fat, but increased markers of hepatic de novo lipogenesis and TAG production. Study limitations include a small sample size and short treatment period. A larger, fully powered study is needed to validate the potential metabolic benefit of combining CE with BZA.

The COVID-19 pandemic has led to major disruptions in the clinical research enterprise. Investigators and staff at the University of Washington and Seattle Children’s Research Institute (SCRI) were surveyed to determine the impact of the pandemic restrictions on their non-COVID-19 clinical research studies. Enrollment and study visits were stopped for over half of the interventional trials. There were both positive and negative impacts of the work restrictions on the professional and personal lives of faculty and staff. Academic and research institutions should consider how best to support investigators and their teams during this pandemic.

ABSTRACT IMPACT: Increase understanding of the types of sponsors responding to the COVID-19 pandemic. OBJECTIVES/GOALS: The COVID-19 pandemic has impacted millions of lives globally. To learn more about this disease and find potential diagnostic, treatment, and preventative products, the healthcare community has initiated a staggering number of clinical trials. Clinicaltrials.gov was reviewed to determine the types of sponsors who are conducting COVID-19 studies. METHODS/STUDY POPULATION: Clinicaltrials.gov was searched using terms ‘COVID-19’ and ‘SARS-Cov-2’. Search results were further defined to include only ‘Interventional’ studies. Of these, only studies with sites located in the United States were selected and for which the ‘Condition’ included at least one of the following terms: ‘COVID’, ‘COVID-19’, ‘Coronavirus’, ‘SARS-Cov-2’, ‘SARS’, or ‘2019-nCoV'. Study sponsors were then categorized as: (1) commercial, (2) academic, or (3) other, based on ‘Sponsor’ information within each study listing. A Google search was conducted for any sponsor that was not easily categorized to obtain additional information to support the proper assessment of sponsor type. The types of sponsors were analyzed over time using the ‘First Posted’ date of each study listing. RESULTS/ANTICIPATED RESULTS: A total of 3662 studies were retrieved, of which 2075 were ‘Interventional’ studies. The studies were further reduced to 681 studies by including only United States sites and the desired ‘Condition’. The percentage of studies from this refined dataset, by sponsor type, were found to be 63% academic, 34% commercial, and 3% other. The relationship between time and sponsor type demonstrated that academic sponsors had the highest percentage of study postings in the first month (March) of the COVID-19 pandemic compared to commercial and other sponsors. Following this first month, academic study postings gradually declined, while commercial sponsors had an increase in postings per month into July, followed by a gradual decline. Few other sponsor type postings were made and occurred primarily in August. DISCUSSION/SIGNIFICANCE OF FINDINGS: The number and timing of listings may be a reflection of study intention and regulatory pathway requirements. Additional variables, such as inconsistent terminology, collaborators, funding, and study start date may influence results. Further analysis may reveal how modification of listing information may result in expedited pandemic response.

ABSTRACT IMPACT: We seek to determine which lymph nodes drain the human brain. OBJECTIVES/GOALS: Lymphatic vessels train lymphatic fluid from the central nervous system (CNS), but the specific lymph nodes that these vessels drain to remains unknown in humans. We intend on using technetium tilmanocept (TcTM)to map the draining lymph nodes of the CNSin humans. METHODS/STUDY POPULATION: Patients having a tumor resected are eligible for the trial. All patients will have TcTM injected intracranially after tumor resection. Six patients will be enrolled in Cohort 1 to define the time course of drainage to the lymph nodes. Patients in Cohort 1 will be imaged with planar LS within 7 hours of injection and the following day. Either 12 or 24 patients will be enrolled into Cohort 2 to localize the draining lymph nodes with SPECT-CT. The optimal imaging timepoint from Cohort 1 will be used for Cohort 2. Patients in Cohort 2 will be stratified depending on if their tumor is in the frontal, parietal, occipital, or temporal lobe. RESULTS/ANTICIPATED RESULTS: We anticipate that we will detect TcTMin the deep cervical lymph nodes after injection into the brain. It is unclear exactly which lymph nodes the tracer will go to. We hypothesize that the results among patients will be similar, but interindividual variation is a possibility. Furthermore, patients with disease in different lobes of the brain may have different lymph drainage patterns. DISCUSSION/SIGNIFICANCE OF FINDINGS: We seek to answer a fundamental question of human anatomy: what lymph nodes drain the human brain? Additionally, knowing which nodes drain the human brain could shape future research of immunotherapy in patients with brain cancer or autoimmune disease such as multiple sclerosis.

Over the last year, COVID-19 has emerged as a highly transmissible and lethal infection. As we address this global pandemic, its disproportionate impact on Black, Indigenous, and Latinx communities has served to further magnify the health inequities in access and treatment that persist in our communities. These sobering realities should serve as the impetus for reexamination of the root causes of inequities in our health system. An increased commitment to strategic partnerships between academic and nonacademic health systems, industry, local communities, and policy-makers may serve as the foundation. Here, we examine the impact of the recent COVID-19 pandemic on health care inequities and propose a strategic roadmap for integration of clinical and translational research into our understanding of health inequities.

ABSTRACT IMPACT: This work will impact participants of clinical trials by better informing them of their trial’s results and their important role within the clinical research process. OBJECTIVES/GOALS: This project aims to equip researchers with an online tool for the development, dissemination, and collection of participant feedback for plain language clinical trial (CT) result summaries (PLCTRS). PLCTRS ensure that participants fully understand their trial’s results and their role in the CT process. METHODS/STUDY POPULATION: This online development platform is a web application made with CSS, HTML, and JavaScript. First, general trial identification information including study aims and eligibility will be input by researchers. Then, they will be prompted with tips and suggestions for composing in plain language and to ensure inclusion of all essential trial information. Next, the platform will disseminate this writing electronically to participants. Participants then provide meaningful feedback on the platform about their comprehension for the researcher, which the platform will aggregate and summarize for revisions. This process of drafting and feedback is repeated until a satisfactory PLCTRS is finalized. RESULTS/ANTICIPATED RESULTS: The anticipated results of this project are overall improved comprehension of clinical trial results by participants. This comprehension will be measured by participants ability to answer certain questions not only regarding trial outcomes, but also about the trial in general. For instance, before and after interacting with the PLCTRS, trial participants will be asked if they can identify which investigational drug was being studied and its possible side effects. This project could anticipate identification of trial elements and results deemed difficult to comprehend by participants; thus they would be better informed after interacting with the platform. DISCUSSION/SIGNIFICANCE OF FINDINGS: This project will ensure that participants better comprehend the trials they participated in beyond the required informed consent process - which only covers their comprehension prospectively. This project seeks to address the gap of ensuring participant comprehension retrospectively.

ABSTRACT IMPACT: The proposed research study will provide critical pilot data on the effect of using the prebiotic (HAMS-AB) on the gut microbiome profile, Beta-cell function and immune markers in humans with T1D. OBJECTIVES/GOALS: The overall objective of this study is to assess how the prebiotic high amylose maize starch that has been acetylated and butyrylated (HAMS-AB) impacts the gut microbiome profile, short chain fatty acid (SCFA) production, glycemia, Beta-cell function/health and immune responses in newly diagnosed youth with type 1 diabetes (T1D). METHODS/STUDY POPULATION: We are performing a pilot randomized cross-over trial. We plan to recruit 12 newly-diagnosed T1D youth with residual Beta-cell function between 12-16 years of age. We will profile the gut microbiome using metagenomics, measure stool SCFA levels using mass spectrometry, assess glycemia using continuous glucose monitoring, assess insulin production using mixed meal tolerance testing, assess Beta-cell stress using proinsulin/C-peptide levels, and test immune responses by examining cytokine levels and frequency, phenotype and function of T cell markers in peripheral blood. RESULTS/ANTICIPATED RESULTS: Thus far, we have enrolled 3 participants, 1 has completed the study. Baseline assessments indicate that we have technical feasibility of performing the above studies and measurements. Recruitment and enrollment are ongoing. We hypothesize that the use of HAMS-AB in newly diagnosed youth with T1D will (i) improve the gut microbiome profile, (ii) increase SCFA production, (iii) improve overall glycemia and Beta-cell function and (iv) modulate the immune system and mitigate autoimmunity. DISCUSSION/SIGNIFICANCE OF FINDINGS: Given the failure to develop a cure for T1D despite multiple completed intervention studies and the unknown long-term effects of immune-modulatory therapy on those at risk for or those diagnosed with T1D, prebiotics such as HAMS-AB may offer a simple, safe, yet inexpensive and tolerated dietary alternative approach to mitigating disease.