All Clinical Trials

A recently completed study suggested that processing speed and attention (PS/A) oriented cognitive training (VSOP) produced robust effect on PS/A and working memory, but not in cognitive control or episodic memory, and long-term effects were overall modest. The proposed R01 renewal proposes to identify additional attributes to further enhance transferred and long-term effects of PS/A training in older adults with amnestic mild cognitive impairment (MCI) by addressing adaptation capacity that underpins adaptive learning and neuroplasticity. The goal of the stage II double-blinded randomized trial is to test whether adding resonance frequency breathing (RFB) training to VSOP will strengthen multiple contributors to adaptation capacity, particularly the central and peripheral pathways of autonomic nervous system (ANS) flexibility, which will strengthen VSOP training effect on cognitive and brain function and slow the progress of dementia in MCI. The central hypothesis is that strengthening adaptation capacity, via improving autonomic nervous system (ANS) flexibility, will enhance neuroplasticity and slow progress of dementia in MCI, since adaptation capacity is critical for neuroplasticity of VSOP, but compromised in neurodegenerative process. Older adults with MCI (n = 114) will be randomly assigned to an 8-week combined intervention (RFB+VSOP), VSOP with guided imagery relaxation (IR) control, and a waitlist IR control, with periodical booster training sessions at follow-ups. Mechanistic and distal outcomes include ANS flexibility and multiple markers of dementia progress. Data will be collected across a 14-month period. The two primary aims are to examine long-term effects of the combined intervention on ANS flexibility (Aim 1), as well as the cognitive, behavioral, and functional capacity (Aim 2). The exploratory aim will be to determine the preliminary long-term effect of the combined intervention on neurodegeneration. This can be a reasonable renewal plan from the completed study, aiming to identify additional attributes to further enhance transferred and long-term effects of cognitive training in MCI. This will be among the first randomized controlled trials to examine a novel, combined intervention targeting adaptation capacity in MCI, with an ultimate goal for slowing neurodegeneration. In addition, research on how to monitor adherence - the extent to which VSOP training is delivered and followed as intended - has been conceptually and methodologically limited. Robust monitoring of adherence to cognitive training requires valid assessment of effective engagement. Here, we apply our well-supported, novel framework of mental fatigability for measuring effective engagement in cognitive training. Mental fatigability, the failure to remain engaged in tasks requiring sustained mental effort, can be captured via measures of self-reported disengagement, increase in reaction time during tasks, and facial expression of negative valence/low arousal. These markers of disengagement relate to ventromedial prefrontal cortex dysfunction. We will apply this framework to advance understanding of the underpinnings of adherence to VSOP training by monitoring the extent of effective engagement while using the training platform. Read Less

This study is a prospective, single center phase II clinical trial in which patients with Severe Aplastic Anemia (SAA) ) will receive a haploidentical transplantation. The purpose of this study is to learn more about newer methods of transplanting blood forming cells donated by a family member that is not fully matched to the patient. This includes studying the effects of the chemotherapy, radiation, the transplanted cell product and additional white blood cell (lymphocyte) infusions on the patient's body, disease and overall survival. The primary objective is to assess the rate of engraftment at 30 days and overall survival (OS) and event free survival (EFS) at 1 year post-hematopoietic cell transplantation (HCT). Primary Objectives * To estimate the rate of engraftment at 30 days after TCR αβ+ T-cell-depleted graft infusion in patients receiving a single dose of post graft infusion cyclophosphamide. * To estimate the overall survival and event free survival at 1-year post transplantation. Secondary Objectives * To calculate the incidence of acute and chronic GVHD after HCT. * To calculate the rate of secondary graft rejection at 1-year post transplantation * To calculate the cumulative incidence of viral reactivation (CMV, EBV and adenovirus). * To describe the immune reconstitution after TCR αβ+ T-cell-depleted graft infusion at 1 month, 3 months, 6 months, 9 months, and 1 year. Exploratory Objectives * To longitudinally assess the phenotype and epigenetic profile of T-cells in SAA patients receiving HCT for SAA. * To assess the phenotype and epigenetic profile of T-cells in DLI administered to SAA patients post HCT. * To longitudinally assess CD8 T cell differentiation status in SAA patients using an epigenetic atlas of human CD8 T cell differentiation. * To examine the effector functions and proliferative capacity of CD8 T cells isolated from SAA patients before and after DLI. * Quantify donor derived Treg cells at different time points in patients received HCT. * Determine Treg activation status at different stages after HCT. * Are specific features of the DLI product associated with particular immune repertoire profiles post-transplant? * How does the diversity and functional profile of the DLI product alter the response to pathogens in the recipient? * Do baseline features of the recipient's innate and adaptive immune cells correlate with post-transplant immune repertoires and response profiles? Read Less

Glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) are the most common primary malignant brain tumors. Survival of patients with these brain tumors is directly related to the extent of resection. Consequently, a great deal of effort has been directed at developing techniques and technologies that allow more extensive, safe resections. This study will test a loupe-based wearable device in the clinical setting and compare its accuracy with a large operative microscope to identify tumor tissues. Postoperative histopathological analysis on tumor tissues will be used as gold standards for comparison. The outcome from this study will be a low-cost, miniaturized, easy-to-operate, loupe-based fluorescence imaging device for intraoperative guidance of brain tumor resection with the same level of accuracy as the large microscope. Read Less

Background: About 5% to 10% of differentiated thyroid cancers become resistant to standard treatment with radioactive iodine. In these cases, treatment options are limited and generally not effective. Researchers want to see if they can better detect thyroid tumors by using a compound called 68Gallium-DOTATATE. This compound may bind to a tumor and make it visible during a positron emission tomography/computed tomography (PET/CT) scan. This information might help guide future research and treatment. Objective: To identify the people with thyroid cancer whose tumors have a high uptake of 68Gallium-DOTATATE as analyzed by imaging with PET/CT. Eligibility: People ages 18 years and older with thyroid cancer that has spread outside of the thyroid. Design: Participants will have a medical exam. They will give blood and urine samples. Some samples will be used for research. Participants will have imaging scans that follow standard of care. These scans may include: CT scan of the neck, chest, abdomen, and pelvis Bone scan Magnetic resonance imaging of the brain, spine, or liver 18-FDG-PET/CT as needed Participants will have a PET/CT scan. They will get an intravenous (IV) line. They will get an IV injection of 68Gallium-DOTATATE. It contains radioactive tracers. The PET/CT scanner is shaped like a large donut. It contains crystals. The crystals pick up small radiation signals that are given off by the tracers. The CT part of the scan uses low-dose x-rays. The pictures made by the scanner show where the tracers are in the body. The session will last 90 minutes. Participation will last for about 3 months.... Read Less

Background: Allogeneic hematopoietic stem cell transplant involves taking blood stem cells from a donor and giving them to a recipient. The transplants are used to treat certain diseases and cancers. Researchers want to see if the transplant can treat VEXAS Syndrome. Objective: To see if stem cell transplants can be successfully performed in people with VEXAS and even improve the disease. Eligibility: People ages 18-75 who have VEXAS Syndrome that has caused significant health problems and standard treatment either has not worked or is not available. Design: Participants will be screened with: Physical exam Medical review Blood and urine tests Heart and lung function tests Bone marrow biopsy Participants will have a chest x-ray. They will have an imaging scan of the head, chest, abdomen, pelvis, and sinus. They will have a bone density scan. They will have a dental exam and eye exam. They will meet with specialists. They will repeat some screening tests. Participants will be admitted to the NIH hospital. They have a central venous catheter put into a vein in the chest or neck. They will receive drugs to prepare their bone marrow for the transplant. They may have total body irradiation. They will receive the donor stem cells through the catheter. They will get other drugs to prevent complications and infections. After discharge, they must stay in the DC area for 3 months for weekly study visits. Participants will have study visits 30, 60, 100, 180, 210, 240, 300, and 360 days later. After that, they will have yearly visits for 2 years and then be contacted yearly by phone.... Read Less

In this study, quantitative characterization of plaque using coronary computed tomographic angiography (CTA) will be used to determine if women who were treated with intensive medical therapy have a greater reduction in the amount and type of cholesterol plaque compared to women receiving usual care and if this results in beneficial changes in clinical symptoms. The study will provide an understanding of how intensive medical therapy works in providing clinical benefit in women with nonobstructive plaque. Read Less

This is a Phase 1/2, multi-center, open-label, dose-escalation and expansion study to evaluate safety and tolerability, PK, pharmacodynamic, and early signal of anti-tumor activity of MDNA11 alone or in combination with a checkpoint inhibitor in patients with advanced solid tumors. Read Less

This study aims to evaluate the effectiveness of offering self-sampled human papillomavirus (HPV) tests in increasing participation in cervical cancer screening, compared to the standard of care clinician-sampled test. The primary study endpoints are (1) patients' acceptability of self-sampled HPV tests vs. clinician-sampled test, and (2) patients' completion of self-sampled HPV test. The secondary study endpoint to be measured is the increase in cervical cancer screenings of any type in the PSH St. Joseph's residency clinic patient population. Read Less

The specific aims of this study are to: 1. Determine if a painless and quick measurement of muscle activity using surface electrodes can help with the diagnosis of ALS. Specifically, we ask if a measure of intermuscular coherence (IMC-βγ), when added to current diagnostic criteria (Awaji criteria), can differentiate ALS from mimic diseases more accurately and earlier than currently possible. 2. Characterize IMC-βγ in neurotypical subjects by age, sex, race, and ethnicity. 3. Follow a cohort of ALS patients longitudinally to determine if IMC-βγ changes with ALS disease progression and whether such changes correlate with functional and clinical scores, or survival. Read Less

The development of stereotactic body radiation therapy (SBRT) for the treatment of stage I non-small cell lung cancer (NSCLC) has inspired a close partnership between thoracic surgery and radiation oncology. In this study, patients with stage I NSCLC will be screened prior to treatment and will be consented after their treatment plan has been determined. Prospectively collected patient-reported outcomes (PROs) will be collected for 3 years or for the duration of the study (whichever is shorter), as will outcomes data. Read Less

The purpose of this study is to determine the safety, efficacy, and pharmacokinetics (PK) of etrasimod for the treatment of moderately to severely active ulcerative colitis in adolescents (≥ 12 years up to \< 18 years of age). Participants who will complete the total 52-week treatment period will have the opportunity to continue in a Long-Term Extension (LTE) Period of up to 4 years (5 years after study enrollment). Read Less

This is a single-center study that aims to earn more about how two different compounds found in food, oxalate and citrate, may affect a person's chances of forming kidney stones. Read Less