Clinical trials

The survival rate for patients with pancreatic cancer remains at a dismal 10% or less at 5 years, and although trials integrating stereotactic body radiation therapy (SBRT) alone have shown improvement in local control, initial invigoration of immune response, and relief of symptom burden, SBRT has not demonstrated any improvement in survival. Preclinical research has established that STAT3 inhibition given concurrently with SBRT and in the maintenance phase acts as a synergistic agent that enhances the pro-inflammatory effects of SBRT while reducing its undesired effects (including fibrosis and immunosuppression). This study exploits the window of opportunity post-chemotherapy to advance the hypothesis that the addition of STAT3 inhibition in combination with SBRT will be safe and will enhance 2-year progression-free survival.

The purpose of the study protocol is to identify imaging biomarkers for brain tissue under high metabolic stress at risk for permanent injury. We will measure oxygen extraction fraction (OEF) and cerebrovascular reactivity (CVR) in participants with and without perturbations in cerebral oxygen delivery over time to determine each parameter's role in clinical and radiologic neurologic outcomes. Measuring OEF can be done with specialized MRI sequences. Measuring CVR requires a vasoactive response, such as carbon dioxide. In order to deliver carbon dioxide evenly and as safely as possible, we will use RespirACT, an MRI-compatible device, to prevent over-breathing carbon dioxide and allow rapid steady-state physiology to minimize total scan time. We will also use a high density diffuse optical tomography (HD-DOT) cap to assess the measurement of OEF and CVR. This study will investigate both regional OEF and CVR simultaneously to understand each marker's unique developmental trajectory and contribution to stroke risk in children. This work will expand insights into mechanisms of stroke in children and assess the feasibility of the HD-DOT cap for obtaining these insights by comparing a cohort of optical CVR and a cohort of MRI CVR. In addition to the MRI and/or HD-DOT cap with RespirAct, participants may also have their vitals measured, complete cognitive testing, and complete a blood draw with a study visit. Participants may be followed for up to three years and may complete both an MRI scan and an HD-DOT scan within 1 week-12 months of each other. Participants may be invited back to repeat MRI and/or HD-DOT scans 1-2 times over the next three years.

Overdose is a national top-three leading cause of pregnancy-associated death, and maternal substance use disorder (SUD) accounts for an estimated $1.5 billion in healthcare spending each year. Treatment with medication and behavioral therapy lowers morbidity and overdose risk. However, studies have shown 55% to 80% of patients stop treatment within one year postpartum. Additionally, as a result of systemic inequities, historically marginalized patients are at greatest risk of overdose or death. We are conducting a study at WashU Medicine and University of Maryland, Baltimore clinics that offer prenatal care, addiction treatment, and extended postpartum support for patients facing the challenges of a SUD. Study participants will complete a structured screening and management of their social needs, and then will be randomly assigned to continue their usual care or to participate in a contingency management program, which provides incentives to continue treatment.

The purpose of this study is to find out which pain medication is more effective in reducing pain after nose surgery (rhinoplasty). The investigators are looking to find the best treatment to reduce discomfort and improve the healing process for patients having nose surgery.

Many people who have had a traumatic brain injury (TBI) struggle to stay connected with others. They often lose friendships, become isolated, and have strained family relationships. This lack of social support is linked to worse physical and mental health, lower quality of life, and even a shorter lifespan. The investigators developed a program where a person with TBI and one close supporter work together with a therapist over 12 weekly sessions. They learn skills in communication, setting shared goals, supporting each other emotionally, and problem-solving, with occasional guidance from a peer mentor who has been through a similar experience. This study will determine whether the program is practical to deliver. We are conducting a pilot study with 30 pairs of participants to test whether sessions run smoothly, whether people show up and stay engaged, and whether participants find the program worthwhile. Based on what they learn, the investigators will refine this program before testing it on a larger scale. If successful, this could lead to a practical, low-risk intervention that improves the lives of people with TBI and the family members and friends who support them.

This study will first evaluate the feasibility of delivering the ENGAGE-TBI intervention in a community setting with adults with TBI.

This study will test the central hypothesis that fat within the muscle, or intramuscular adipose tissue (IMAT), exhibits elevated damage and pro-inflammatory signaling with aging, both of which are reduced by progressive resistance exercise (PRE). Sixteen older adults 65-80 years old will be recruited and complete a 12 week calf PRE intervention. Calf muscle strength, composition (measured by computed tomography) and muscle biopsies will be collected before and after the intervention. Histology, transcriptomic and secretomic tests will be completed to assess signs of damage and inflammation.

Purpose: This study aims to improve asthma care by helping clinicians at community health centers prescribe a guideline-recommended treatment called SMART (Single Maintenance and Reliever Therapy). The investigators will provide training and resources to clinicians, give feedback on prescribing patterns, and offer educational tools for patients and providers. The investigators will roll out these resources in stages across clinics. The study will measure how well the program helps clinicians prescribe SMART therapy and whether it reduces asthma exacerbations in patients.

\- The investigators propose a clinical trial to evaluate the impact of annual shared decision making for PSA screening, supported by system-level enhancements to promote evidence-based care: * Defined referral thresholds within the health maintenance reminder, aligned with clinical risk stratification per NCCN guidelines. * Enhanced clinical decision support (CDS) tools to reduce provider variation and ensure guideline-concordant screening and referral practices. * The goal is to reduce late-stage presentation without increasing overdiagnosis-ensuring that prostate cancer screening is both accessible and clinically effective.

The goal of this clinical trial is to test whether light therapy is effective for reducing symptoms in young adults with OCD and late bedtimes (1am or later). The main question\[s\] it aims to answer are: Does light therapy reduce OCD symptoms? Does light therapy advance the circadian clock? If there is a comparison group: Researchers will compare a higher dose of light therapy to a lower dose to see if dose amount affects symptom reduction. Participants will asked to: 1. Wear light therapy glasses for 1 hour each morning and complete a daily light therapy log for 5 weeks 2. Track their sleep every day with a wearable monitor and an electronic sleep diary for 5 weeks 3. Complete a 1-time assessment of sensitivity to light exposure 4. Complete self-report measures of OCD 4 times/day at baseline (2 weeks), mid-treatment (1 week), and end of treatment (1 week)

The goal of this study is to learn about brain connectivity and if massaging babies shortly after birth has an impact. Half of the recruited babies will receive massage daily while the other half will not, and differences will be observed.

This single arm pilot phase I study with safety run-in is designed to estimate the safety and efficacy of a familial mismatched or haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using a novel graft modification technique (selective αβ-TCR and CD19 depletion).

This study is a dynamically adjustable prospective longitudinal study designed to capture biospecimen (biopsy, blood, surgical) and multimodal treatment-related data (imaging, dosimetry, clinical) before, during, and after treatment with definitive-intent chemoradiotherapy for patients with locally advanced cervical and pancreatic cancer.

The study is an open-label phase I/II clinical trial. The study will enroll patients to receive neoadjuvant SBRT plus 1 or 2 doses of neoadjuvant pembrolizumab with concurrent ficerafusp alfa (4 doses) prior to definitive surgical resection for high-risk, locoregionally advanced HPV-negative head and neck squamous cell carcinoma (HNSCC). Approximately 6 weeks after end of SBRT, patients will undergo standard of care (SOC) surgical resection followed by SOC adjuvant chemoradiation per National Comprehensive Cancer Network (NCCN) guidelines. Adjuvant therapy is not part of this study and therefore is not dictated by study protocol.

The purpose of this study is to increase screening mammography among Black women by implementing and evaluating a culturally tailored patient-centric program designed to address barriers to screening. By performing a randomized clinical trial, this study aims to develop effective strategies to improve adherence to screening mammography and contribute to reducing health disparities in breast cancer outcomes.

Although small cell lung cancer (SCLC) responds dramatically to initial platinum-based chemotherapy, recurrences are nearly universal. The addition of atezolizumab, an immune checkpoint inhibitor, to front-line chemotherapy has recently demonstrated an improvement in overall survival (OS) in extensive stage SCLC (ES-SCLC). Subsequent lines of therapies are associated with modest efficacy in patients with relapsed disease, and the median overall survival is still 12 to 13 months at best. Cirtuvivint is a small molecule inhibitor of the CDC2-like kinases (CLKs) and dual-specificity tyrosine-regulated kinases (DYRKs); inhibiting CLKs and DYRKs has been shown in preclinical models to cause tumor growth inhibition and sensitize cancer cells to cytotoxic chemotherapy. This study is testing the hypothesis that adding cirtuvivint to chemotherapy in patients with relapsed SCLC will be well tolerated and improve the response rate and progression-free survival (PFS).

Inspired by the ongoing Pink \& Pearl Campaign, the breast radiology service of Christian Hospital in north St. Louis County will partner with Siteman Cancer Center to pilot this campaign in its mammography clinics in order to promote awareness, referral, and completion of lung cancer screening (LCS) among eligible women. This campaign leverages established infrastructure such as nurse navigation and referral to screening or primary care for further shared decision-making on cancer screening. The purpose of this study is to evaluate the effectiveness of the Pink \& Pearl Campaign in improving LCS uptake among LCS-eligible women undergoing mammography at Christian Hospital. This evaluation is grounded in the Integrated Screening Action Model that depicts individual- and environmental-level influences on the screening behavior process. Using an explanatory sequential mixed methods design, which combines both quantitative and qualitative approaches, our specific aims for this proposal are to: a) assess whether the Pink \& Pearl Campaign increases referrals and uptake/completion of LCS among LCS-eligible women undergoing screening mammography; b) determine median time-to-screening after referral to LCS; and c) evaluate individual and health system factors influencing LCS uptake and implementation outcomes of the campaign. These implementation outcomes will help identify whether the campaign was put in place successfully or not. This proposal will inform strategies for integrating cancer screening programs to improve poorly performing programs like LCS.

The investigators proposal is ripe for executing as the investigators seek to leverage this "natural experiment" initiated by the BJC health system to evaluate the effectiveness of the Pink \& Pearl Campaign as an implementation strategy to promote lung cancer screening (LCS) uptake among LCS-eligible women undergoing mammography at BJC West County. This evaluation is grounded in the Integrated Screening Action Model that depicts individual- and environmental-level influences on the screening behavior process. Using an explanatory sequential mixed methods design, which combines both quantitative and qualitative approaches, the research questions and specific aims for this proposal are to: a) evaluate the baseline prevalence of LCS among LCS-eligible women; b) assess whether the Pink \& Pearl Campaign increases referrals and uptake/ completion of LCS among LCS-eligible women undergoing screening mammography; and c) evaluate individual and environmental factors influencing LCS uptake, and implementation outcomes of the campaign. These implementation outcomes will help identify whether the campaign was put in place successfully or not. This proposal will inform strategies for integrating cancer screening programs to improve poorly performing programs like LCS.

Insulin is a hormone that is made by β-cells in the pancreas and when released into the bloodstream helps control blood sugar levels. Insulin release is regulated by electrical activity in the β-cell which is generated by the ATP-sensitive potassium (KATP) channel. While reduced KATP activity is associated with increased insulin secretion, animals lacking KATP exhibit reduced secretion. This crossover from hypersecretion to undersecretion with KATP loss mirrors insulin secretion during type 2 diabetes. Intriguingly, evidence from cell and animal models suggest that chronically stimulated β-cells can lose KATP revealing a possible role for KATP loss in the failure of insulin secretion and poor control of blood sugar observed in type 2 diabetes. This study will therefore examine insulin responses following ingestion of a single dose of a sulfonylurea called glipizide that inhibits KATP channels in people with and without type 2 diabetes. The goal is to determine whether KATP channel activity is reduced during type 2 diabetes progression.

Study researchers think that a drug called enasidenib may help people with clonal cytopenia of undetermined significance (CCUS) because the drug blocks the mutated IDH2 protein, which may improve blood cell counts. The purpose of this study is to find out whether enasidenib is a safe and effective treatment for CCUS.

The project is a multisite, three-group randomized control trial (RCT) with equal and parallel mixed-methods analysis that allows standardized measures combined with rich qualitative data to test hypotheses and answer research questions. Family caregivers (FCGs) of hospice cancer patients will be recruited and randomized into one of three groups: usual hospice care only (UC), usual care online support group (UCOSG) (without communication strategies), and the CHOOSE intervention group (with communication focus).

This phase Ib single-center open-label de-escalation study uses a modified 3+3 design to determine the safety, tolerability, and recommended phase II dose (RP2D) of the combination of standard of care Sip-T and N-803 in patients with metastatic androgen pathway modulation resistant (mAPMR) prostate cancer. Patients will receive treatment for up to 8 weeks.

The aim of this study is to evaluate, in adults with HFrEF in Sri Lanka, the effects of an HFrEF polypill implementation strategy on the composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations, compared with usual care over a minimum of 12-months of follow-up. Primary outcome of the study: 1\) Composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations over study duration Secondary outcomes of the study: 1. Rate of cardiovascular disease mortality over study duration 2. Rate of recurrent heart failure hospitalizations over the study duration 3. Rate of all-cause mortality over the study duration 4. Change in left ventricular ejection fraction at 12-months and end of study assessed by transthoracic echocardiogram 5. Change in BNP levels at 12 months and end of study 6. Change in overall and domain specific health-related quality of life at 12-months and end of study assessed by a translated validated version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) 7. Change in physician-reported New York Heart Association class at 12-months and end of study 8. Adherence to guideline-directed medical therapy assessed by pill count and MARS-5 questionnaire at baseline, 1-, 6-, 12-months, and end of study. Persistence assessed as continuation of assigned therapy at each follow-up visit. Dose optimization assessed as proportion achieving target doses (Strength 3 of the polypill, or comparable individual GDMT doses in the comparator arm) at 6-, 12-months, and end of study. Safety outcomes: 1. Proportion of participants with serious adverse events according to Good Clinical Practice guidelines over study duration 2. Proportion of participants with adverse events of special interest over study duration 3. Proportion of participants with adverse events leading to HF drug discontinuation over study duration 4. Mean change from baseline to 12-months and end of study in serum potassium (mEq/L) 5. Mean change from baseline to 12-months and end of study in serum creatinine (mg/dL) Participants will be randomly assigned 1:1 stratified by sex and site to one of two groups, intervention (experimental arm) or usual care (control arm). The intervention group will be given four guideline-recommended medications for heart failure with reduced ejection fraction, combined in one over-encapsulated pill, with three dose strength options. Both groups will be observed over a minimum of 12-months of follow-up to assess key outcomes.

Substance use during pregnancy is a leading cause of maternal morbidity and mortality in the United States, with 55-80% of postpartum patients disengaging from substance use disorder (SUD) treatment within one year of delivery. Structural and social determinants of health, including housing instability, transportation barriers, and limited childcare access, further exacerbate disparities in treatment retention. This pilot study, conducted in two specialized prenatal care clinics, evaluates the feasibility and acceptability of two integrated strategies to promote sustained engagement in recovery-oriented services during the perinatal and postpartum periods. Aim 1 implements a standardized social needs screening and referral protocol to connect patients with community-based supports. Aim 2 pilots a contingency management intervention to incentivize recovery-supportive behaviors. Findings will inform the design of a larger multi-site randomized controlled trial to evaluate the impact of these interventions on treatment retention, overdose prevention, and maternal-infant health outcomes.

This project will compare two training approaches for US Preventive Services Task Force recommended obesity care in Federally Qualified Health Centers (FQHC) across four aims. Aim 1 compares patient-level effectiveness \[i.e., patient relative weight change and the proportion of patients who achieve clinically significant weight loss\]. Aim 2 compares reach (patient treatment utilization). Aim 3 compares primary care provider (PCP) referrals to USPSTF-recommended care at 12 (adoption) and 24 months (maintenance) and short- and long-term changes in provider obesity care competencies . Aim 4 compares implementation and service costs.