The investigators will focus on three cohorts of brain tumor patients aged, 4-18 years, to answer two critical questions: 1) Can the investigators acquire high quality data relevant to cognitive function during the peri-diagnostic period and, 2) can the investigators develop predictive models for cognitive outcomes using serial examination of functional imaging and cognitive function. Any patient with a newly diagnosed brain tumor aged 4-18 will be eligible for enrollment in cohort 1. Only patients with previously diagnosed tumors of the posterior fossa will be eligible for cohort 2. For cohort 3, eligible patients will include patients with a clinical diagnosis of posterior fossa syndrome with physical impairments that prohibit completion of the NIH Toolbox Cognitive Battery. The investigators have decided to expand the eligible tumor types to better capture the most significant deficit variability that can be caused by tumors outside the posterior fossa. Thus, this focus will provide a platform to analyze the impact that different tumor types and different standard treatments have on cognitive dysfunction. The rationale for inclusion of subjects on cohort 3 is that posterior fossa syndrome is one of the most cognitively devastating diagnoses following a posterior fossa surgery. The causes of posterior fossa syndrome and unknown and there are currently no interventions to improve symptoms. RsfcMRI would offer a novel and non-invasive assessment of posterior fossa syndrome patients by assessing connectivity within and outside of the cerebellum. Expanding the tumor eligibility will allow us to further explore the effect tumor location will have on cognitive testing and rsfcMRI. Here, repeated evaluations on and off therapy will provide the necessary data points to establish trajectories of cognitive development and recovery in this population.

Type: Interventional

Start Date: Oct 2016

open study

This study evaluates the feasibility and preliminary effects of precision tobacco treatment, compared to usual care, on promoting tobacco treatment in oncology patients and providers in the oncology care setting. The precision treatment intervention includes personalized tobacco treatment recommendations using the patient's clinical, genetic, and biomarker information. This intervention may increase patient receipt of tobacco treatment, patient medication use, and patient smoking abstinence at 6 months.

Type: Interventional

Start Date: Sep 2025

open study

The investigators hypothesize that brief behavioral therapy and targeted propofol infusion in depressed geriatric patients will augment subsequent slow wave sleep and improve clinical and cognitive outcomes. The team will recruit 70 participants for a double-blinded placebo controlled randomized controlled trial. Two propofol infusions, 2-6 days apart, will be administered, targeting either a low propofol dose arm (minimal EEG slow waves, brain effect-site concentration 1-2 mcg/ml) or moderate dose propofol arm (maximal induction of EEG slow waves, brain effect site concentration of >2.5 mcg/ml). The pharmacologic intervention will be paired with 3-4 sessions of Brief Behavioral Therapy for Insomnia for all participants. To minimize bias, there will be no specific gender or ethnic background consideration for enrollment. This will be a single site investigation at Washington University Medical Center.

Type: Interventional

Start Date: Mar 2025

open study

The primary purpose of this study is to evaluate the anti-tumor activity of TLN-254 monotherapy in participants with relapsed or refractory T-cell lymphoma.

Type: Interventional

Start Date: Dec 2024

open study

A serious consequence of systemic diffuse large B-cell lymphoma (DLBCL) is secondary central nervous system (CNS) relapse, which occurs in approximately 5% of all patients. Many CNS relapses occur within the first year after completion of frontline treatment and are associated with significantly increased mortality; thus, it is important to tailor frontline treatment to provide prophylaxis against CNS relapse in those patients who are determined to be high-risk. Autologous stem cell transplantation (ASCT) is standard of care for patients with DLBCL who relapse one year or more after first remission, and it has been shown to improve progression-free survival for patients with primary CNS lymphoma. The four-drug BEAM regimen (carmustine, etoposide, cytarabine, and melphalan) is the preferred conditioning regimen for DLBCL patients undergoing ASCT; however, patients with primary CNS lymphoma receive thiotepa plus carmustine as their conditioning regimen due to its better CNS penetration. This study tests the hypothesis that consolidation thiotepa/carmustine ASCT in first complete remission will reduce the risk of CNS relapse in transplant-eligible patients with DLBCL with no prior CNS disease at high risk of secondary CNS recurrence.

Type: Interventional

Start Date: Jan 2025

open study

This phase 2 study aims to confirm the efficacy seen in the prior phase 1 trial, and further contribute to this effort through the collection of leukemia cells pre- and post- in vivo IFN-γ therapy. As in the previously conducted phase 1 trial, this trial will test whether leukemia blasts were responsive to IFN-γ in vitro and in vivo, with single-cell RNA sequencing (scRNAseq) conducted to understand the transcriptomic changes induced by IFN-γ in leukemia cell subsets, including those with stem cell characteristics.

Type: Interventional

Start Date: Sep 2024

open study

This phase III trial compares the addition of an immunotherapy drug (durvalumab) to usual chemotherapy versus usual chemotherapy alone in treating patients with MammaPrint High 2 Risk (MP2) stage II-III hormone receptor positive, HER2 negative breast cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as paclitaxel, doxorubicin, and cyclophosphamide work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. There is some evidence from previous clinical trials that people who have a MammaPrint High 2 Risk result may be more likely to respond to chemotherapy and immunotherapy. Adding durvalumab to usual chemotherapy may be able to prevent the cancer from returning for patients with MP2 stage II-III hormone receptor positive, HER2 negative breast cancer.

Type: Interventional

Start Date: Nov 2023

open study

This is a randomized, open label, comparative Phase II trial being conducted to determine whether fecal microbiota transplant using Penn Microbiome Therapy (PMT) products helps standard therapy eradicate antibiotic-resistant bacteria.

Type: Interventional

Start Date: Aug 2024

open study

Prospective, non-randomized, multi-center clinical investigation of the NEXUS™ Aortic Arch Stent Graft System (NEXUSTM) for the treatment of thoracic aortic lesions involving the aortic arch with a proximal landing zone, native or previously implanted surgical graft, in the ascending aorta and with a brachiocephalic trunk native landing zone.

Type: Interventional

Start Date: Oct 2020

open study

This open-label, multicenter, within-participant dose escalation study examining up to 2 dose levels of DISC-3405 will assess the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of DISC-3405 in participants with polycythemia vera (PV).

Type: Interventional

Start Date: Aug 2025

open study

The goal of this clinical trial is to evaluate the effectiveness and safety of bilateral stimulation of the subcallosal cingulate white matter (SCCwm) using Deep Brain Stimulation (DBS) as an adjunctive treatment of non-psychotic unipolar Major Depressive Disorder (MDD) in adults.

Type: Interventional

Start Date: Sep 2024

open study

The goal of this quasi-experimental interventional study is to determine the effectiveness of a multifaceted stewardship intervention in reducing overall vancomycin use in five tertiary care Pediatric Intensive Care Units (PICU). There are two groups of subjects in this study: PICU clinicians/sepsis stakeholders and patients admitted to one of the participating PICUs during the study period. The intervention will at a minimum include: - Implementation of a clinical guideline indicating when vancomycin should and should not be used - Unit-level feedback on overall vancomycin use within and across centers - Clinician education.

Type: Interventional

Start Date: Aug 2023

open study

This is a pilot study of the tolerability and safety of neoadjuvant dapagliflozin for patients with unfavorable intermediate, high-risk, or very high-risk prostatic adenocarcinoma prior to radical prostatectomy. The primary hypothesis is that four weeks of daily dapagliflozin prior to surgery is well-tolerated and safe to use in this patient population. The investigators also hypothesize that dapagliflozin will be efficacious in resulting in tumor shrinkage on pre-operative imaging and will result in tumor necrosis at prostatectomy.

Type: Interventional

Start Date: Jun 2024

open study

This randomized trial will evaluate the effect of fenofibrate compared with placebo for prevention of diabetic retinopathy (DR) worsening through 6 years of follow-up in eyes with mild to moderately severe non-proliferative DR (NPDR) and no CI-DME at baseline. In addition to evaluating efficacy, this study aims to evaluate the feasibility of a model for ophthalmologists to prescribe or collaborate with a primary care provider such as an internist/endocrinologist to prescribe and monitor the drug safely. If this study demonstrates that fenofibrate is effective for reducing the onset of proliferative diabetic retinopathy (PDR) or and the results are adopted by the community of retina specialists, a new strategy to prevent vision threatening complications of diabetes could be widely adopted. Widespread use of an oral agent effective at reducing worsening of DR would decrease the numbers of patients who undergo more invasive and much more expensive treatment for DR and who are consequently at risk for side effects that adversely affect visual function. This study will also assess the relationship of glycemic variability, as measured by continuous glucose monitoring with DR outcomes. Ancillary studies will characterize functional and structural outcomes in this cohort.

Type: Interventional

Start Date: Mar 2021

open study

The purpose of this research study is to better understand how blood flow and metabolism change can influence brain development in the early decades of life. We will examine brain blood flow and metabolism using magnetic resonance imaging (MRI). The brain's blood vessels expand and constrict to regulate blood flow based on the brain's needs. The amount of expanding and contracting the blood vessels can do varies by age. The brain's blood flow changes in small ways during everyday activities, such as normal brain growth, exercise, or deep concentration. Significant illness or psychological stress may increase the brain's metabolic demand or cause other bigger changes in blood flow. If blood vessels are not able to expand to give more blood flow when metabolic demand is high, the brain may not get all of the oxygen it needs. In extreme circumstances, if the brain is unable to get enough oxygen for a long time, a stroke may occur. Sometimes small strokes occur without other noticeable changes and are only detectable on an MRI. These are sometimes called "silent strokes." In less extreme circumstances, not having as much oxygen as it wants may cause the brain to grow and develop more slowly than it should. One way to test the ability of blood vessels to expand is by measuring blood flow while breathing in carbon dioxide. Carbon dioxide causes blood vessels in the brain to dilate without increasing brain metabolism. During this study participants may be asked to undergo a blood draw, MRI, and potential neuropsychological assessments. It is also possible that the study team will use a special mask to control the amount of carbon dioxide the participants breathe in so they don't breathe in too much.

Type: Interventional

Start Date: Oct 2019

open study

This is a three-part study evaluating the safety and efficacy of a PSMA-directed radioantibody (rosopatamab tetraxetan, conjugated to either In-111 or Ac-225). Part 1 will consist of one administration of In-111-rosopatamab tetraxetan to characterize the biodistribution of the radioantibody to target organs and prostate cancer lesions. Participants then will be enrolled into either Part 2 (Dose Optimization) or Part 3 (Dose Escalation and Expansion) depending on their prior treatment history. Participants qualifying for Part 2 will be randomized to receive Ac-225 rosopatamab tetraxetan in a single fractionated cycle (dose administration on Day 1 and Day 15) at either 45 or 60 kBq/Kg. Participants qualifying for Part 3 must have received prior Lu-177-PSMA-radioligand therapy and will receive Ac-225 rosopatamab tetraxetan in a single fractionated cycle at 45, 55, or 60 kBq/Kg. Dose limiting toxicities (DLTs) will be monitored in Part 3 to determine the recommended phase 2 dose (RP2D), and the study may enroll additional participants to be treated with the RP2D dose level. Participants enrolled into any part will attend study visits which will include blood samples, electrocardiogram (ECG), radiographic imaging, and physical examinations along with other assessments.

Type: Interventional

Start Date: Aug 2024

open study

Aim 1. To determine the factors contributing to pain in patients with chronic pelvic pain with and without endometriosis Aim 2. To determine the changes following endometriosis lesion removal surgery in pain and sex hormone levels. Aim 3. To identify factors predicting clinical pain reduction after lesion removal surgery. Additional exploratory aims might compare subgroups of patients such as patients with vs. without endometriosis, with vs. without additional chronic pain syndromes, and with vs. without hormonal treatment. In addition, the role of lesion-specific immune signatures and psychological factors on pain will be explored. Patients with pelvic pain potentially due to endometriosis will complete questionnaires including social, health, behavioral, and psychological questionnaires. Patients will also complete a 2.5 hours study visit of psychophysical assessments of thermal and pressure stimuli. In addition, blood, urine, and saliva samples will be collected for hormonal, immune, and genetic analyses. Additional samples might be collected and stored for future analyses. For some participants, these procedures will be completed several times, including before the surgery as well as 3 months, 6 months and 1 year after surgery. After the surgery, surveys assessing pain and other symptoms will be sent every week on the first month and then monthly for 1 year. In addition, during the surgery, biopsies will be collected and analyzed to determine hormonal, immune and genetic factors. For adolescents, a parent/legal guardian will be asked to assist in completing some of the health-related surveys (i.e., physical developmental survey, health survey, migraine history survey).

Type: Observational

Start Date: Sep 2023

open study

This phase I trial tests the safety, side effects, and best dose of ex vivo expanded natural killer cells in treating patients with cancerous (malignant) tumors affecting the upper part of the brain (supratentorial) that have come back (recurrent) or that are growing, spreading, or getting worse (progressive). Natural killer (NK) cells are immune cells that recognize and get rid of abnormal cells in the body, including tumor cells and cells infected by viruses. NK cells have been shown to kill different types of cancer, including brain tumors in laboratory settings. Giving NK cells from unrelated donors who are screened for optimal cell qualities and determined to be safe and healthy may be effective in treating supratentorial malignant brain tumors in children and young adults.

Type: Interventional

Start Date: May 2024

open study

The purpose of this research study is to evaluate adult children of parents with and without Alzheimer's disease which represent an ideal population for investigating the biological changes that precede the clinical onset of AD. The investigators will be imaging the brain to detect the presence of amyloid deposits (plaques in the brain). Amyloid is a protein that may be related to dementia of Alzheimer's disease (DAT).

Type: Observational

Start Date: Jun 2021

open study

The overall goal of the randomized control trial (RCT) will be to evaluate the efficacy of modifications to a web-based tool for patient decision-making regarding return of genomic results that will more closely focus on rare cancers. Participants will be given access to a web-based decision aid (or a standard control) that guides participants in making decisions about what type of genomic results they would like to receive from testing performed in the PE-CGS study (NCT06340646).

Type: Interventional

Start Date: Apr 2025

open study

This phase of the protocol (protocol part B), seeks to evaluate the new formulation in healthy normal volunteers to confirm the new formulation provides comparable human dosimetry to which was seen and published in protocol part A. Additionally, the new formulation will be studied utilizing an expanded patient population to include patients with confirmed diagnosis of multiple myeloma (MM), low-grade lymphoma, or MM and lymphoma patients who are status post bone marrow transplant (BMT) with negative imaging and suspected recurrence.

Type: Interventional

Start Date: Feb 2025

open study

With modern therapy, the survival rate for pediatric brain tumor patients has significantly improved, with over 70% of patients surviving their disease. However, this progress often comes at the cost of substantial morbidity, with cognitive deficits being the primary obstacle to independent living. Robust predictors of cognitive decline and a comprehensive understanding of the underlying mechanisms of cognitive injury remain elusive. This study will prospectively investigate alterations in brain resting state networks following radiation therapy using functional imaging. The hypothesis is that radiation therapy leads to dose-dependent alterations in functional connectivity in the networks associated with higher level cognition, ultimately leading to cognitive decline.

Type: Observational

Start Date: Jul 2024

open study

The goals of this research study are to: 1) understand why some people with obesity are protected from developing conditions such as type 2 diabetes and cardiovascular disease while others are more likely to develop obesity-related conditions; 2) assess the effect of small extracellular vesicles (sEVs also called exosomes), obtained from human participants, on metabolic function in cultured cells and in mice.

Type: Interventional

Start Date: Jun 2023

open study

The Autoimmune Liver disease Network for Kids (A-LiNK) is a multi-institutional group with the mission to deliver the best care to kids with pediatric autoimmune liver disease (AILD). This study will establish a shared clinical registry and a learning health network for the participating sites focusing on collecting and transmitting clinical measurement data, information about processes, and participation in an improvement collaborative. Pediatric Autoimmune Hepatitis (AIH) and Primary Sclerosing Cholangitis (PSC), represent a spectrum of AILD which present unique diagnostic and therapeutic challenges.A lack of accepted guidelines for disease monitoring or symptom management results in wide treatment variation with liver transplants indicated in refractory, progressive disease. The aims of A-LiNK are to: 1.) Create a learning health network focused on patient-centered outcomes research characterized by transparent sharing among centers, common priorities, and feasible plans for implementing new practices; 2) shift from traditional investigator-driven study to a patient and family-centered approach, and 3.) improve clinical outcomes and quality of life for pediatric AILD patients.

Type: Observational [Patient Registry]

Start Date: Apr 2022

open study

The investigators will aim enroll participants into our study within 3-6 months after their parent study visit so the investigators can utilize some key data points (e.g. PD-MCI diagnosis, rs-fcMRI data) from that study. PD participants will participate in a single-blind RCT with two treatment arms: process training and strategy training (Fig 4). They will complete pre-training assessment (Pre), be randomized to treatment arm (1:1 ratio stratified by sex), and then complete 8 training sessions over an 8-week period. They will return within 1 week for post-training assessment (Post) and then will complete Follow-up (FU) assessments via web or mailed survey 3 and 6 months after training ends. They will complete a 12mo FU assessment in person in conjunction with their annual parent study visit. HC participants will complete prospective memory assessment at one time point coinciding with (or within 3-6 months of) their parent study visit to determine whether any relationships observed between rs-fcMRI data and prospective memory are specific to PD.

Type: Interventional

Start Date: Nov 2021

open study