All Clinical Trials

Diabetes type two is a debilitating disease that leads to chronic morbidity such as accelerated microvascular disease. Accelerated microvascular disease may produce blindness, end stage renal disease, myocardial infarction, stroke, and limb ischemia. Strategies to prevent or delay microvascular disease have the potential to improve the lives of millions and prevent catastrophic illness. The major focus of prevention of microvascular disease in diabetes has been on the endothelium and its role in protection of blood vessels. An unexpected means to prevent microvascular disease in diabetes may be coupled to the function of vitamin C in red blood cells (RBCs) of diabetic subjects. Based on new and emerging data, vitamin C concentrations in RBCs may be inversely related to glucose concentrations found in diabetes. Based on animal data, we hypothesize that RBCs with low vitamin C levels may have decreased deformability, leading to slower flow in capillaries and microvascular hypoxia, the hallmark of diabetic microangiopathy. Low vitamin C concentrations in RBCs of diabetic subjects may be able to be increased, by using vitamin C supplements. Findings in animals may not accurately reflect effects in humans because of species differences in mechanisms of vitamin C entry into RBCs. Therefore, clinical research is essential to characterize vitamin C physiology in RBCs of diabetic subjects. In this protocol we will investigate physiology of vitamin C in RBCs of diabetic subjects as a function of glycemia, without vitamin C supplementation (stage 1) and with vitamin C supplementation (stage 2). We will screen type II diabetic subjects on insulin and/or oral hypoglycemic medication(s) and select those with hemoglobin A1C concentrations of less than or equal to 12%. Selected subjects may be hospitalized twice, each time for approximately one week. The primary objective of the first hospitalization (stage 1) will be to evaluate the effect of hyperglycemia on vitamin C RBC physiology regardless of baseline vitamin C concentrations (without any vitamin C supplementation). The second hospitalization (stage 2) investigates the effect (if any) of vitamin C supplementation to changes in RBC physiology during euglycemic and hyperglycemic states. As inpatients, subjects will have two venous sampling periods each of approximately 24 hours. On admission, subjects may be fitted with continuous glucose monitors (CGMs), oral hypoglycemic agents will be discontinued, and basal-bolus insulin regimen initiated. Insulin doses will be clinically determined and titrated to achieve euglycemia (fasting and pre-meal glucoses \<140mg/dl) prior to the first sampling period (euglycemic sampling). The first sampling period will be performed under conditions of euglycemic control for 24 hours. The second sampling period will be performed under controlled hyperglycemia induced by withholding basal and bolus insulin and providing a high carbohydrate load diet (70-75% carbohydrate). Correction-scale insulin will be provided for glucoses \>350-400mg/dl. Hyperglycemia will not exceed 9 hours, and will be reversed by reinstituting insulin. During the two sampling periods, samples will be withdrawn via venous catheter for RBC deformability, vitamin C concentrations and other related research studies. Following completion of stage 1, subjects considered for participation in stage 2 will be provided a prescription for vitamin C 500mg twice daily. Given that vitamin C and vitamin E are related antioxidants, and that both vitamins appear to be associated with RBC rigidity, diabetic subjects may also be given a prescription for 400 international units (IU) of vitamin E (RRR alpha tocopherol) daily. Subjects will continue vitamin C and E supplementation for a minimum of 8 weeks depending on RBC vitamin C concentrations. To evaluate any effect of vitamin E supplementation, plasma and RBC vitamin E levels may be measured concurrently with vitamin C levels during various phases of stages 1 and 2. All subjects will be seen as outpatients at biweekly or monthly intervals with regular measurement of plasma and RBC vitamin C concentrations. Target RBC vitamin C concentration \>30uM is required prior to stage 2 inpatient sampling studies. Vitamins C and E supplementation will be discontinued upon inpatient admission for stage 2. Risk of both vitamin supplements are minimal as both supplementation doses are safe. Outcomes are to measure RBC rigidity and vitamin concentrations before and after supplementation. After a minimum of 8 weeks (depending on RBC vitamin C levels), subjects will be hospitalized again, and sampling repeated as described. In this manner, each subject serves as his/her own control, and deformability of red blood cells can be determined in relation to glycemia and to vitamin C concentrations in RBCs and plasma. ... Read Less

This phase I trial tests safety, side effects and best dose of iadademstat with azacitidine and venetoclax for the treatment of patients with acute myeloid leukemia (AML) who have not receive treatment (treatment naive). Chemotherapy drugs, such as iadademstat and azacitidine work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving iadademstat with azacitidine and venetoclax may be safe and tolerable in treating patients with treatment naive AML. Read Less

Background: - By the time diseases of the retina are detected, serious damage has often already been done. Researchers want to find better ways of viewing the retina. One way called adaptive optics may help detect problems earlier. Objectives: - To study if adaptive optics can help find better ways to diagnose, treat, and manage retinal diseases. Eligibility: * People over age 12 with an eye disease. * Healthy volunteers over age 12. Design: * Participants will be screened with medical history and eye exams. These may include dilating pupils and taking pictures of the eyes. * Participants will have 1 or more study visits. They will have: * Medical and eye history. * Questions about their medications. * Eye exam including pupil dilation. * Adaptive optics imaging. After dilation, participants sit still while looking into an adaptive optics instrument. They look at specific places and images are taken of their retina. * They may also have: * More images. * Perimetry. Participants look into a lens and press a button when they see a light. * Color vision tests. * Electroretinogram. Participants will get numbing eye drops and special contact lenses. A small metal electrode will be put on their forehead. They will look at flashing lights and try not to blink. Read Less

The goal of this study is to identify a safe and tolerated dose of the orally administered DHX9 inhibitor ATX-559. In addition, this study will evaluate the pharmacokinetics, pharmacodynamics and preliminary antitumor activity of ATX-559 in patients with advanced solid tumors and molecularly defined cancers. Read Less

This phase Ib trial studies the side effects of nivolumab and to see how well it works in treating patients with autoimmune disorders and cancer that has spread to other places in the body or cannot removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Read Less

The purpose of this study is to investigate the effectiveness of various oral analgesic regimens in minimizing post-operative pain and discomfort in young children following dental rehabilitation under general anesthesia (DRGA). In this randomized controlled trial, three analgesic regimens following DRGA in Franciscan Children's Hospital will be compared using both self-report and behavioral measures. The analgesic therapies to be investigated are ibuprofen monotherapy, alternating ibuprofen and acetaminophen dual-therapy, and combined ibuprofen and acetaminophen dual-therapy. For the purposes of this study, combined therapy is defined as the simultaneous administration of acetaminophen and ibuprofen at regular intervals, whereas alternating therapy is defined as one analgesic (acetaminophen or ibuprofen) administered within a 3 hour interval of the other. Read Less

Background: People with Idiopathic CD4 lymphopenia (ICL) have lower numbers of a type of white blood cell called CD4 cells. White blood cells fight against infections. Low levels of CD4 cells may make a person more likely to get sick. There are no approved treatments for ICL. Researchers think a drug called belimumab may be able to help in specific situations. Objective: To see if belimumab is safe for people with ICL. Eligibility: People ages 18-70 who have ICL and are participating in NIH protocol 09-I-0102 (EPIC) Design: Participants will be screened with: Medical and medication history Physical exam Questionnaire about mental health and depression Blood and urine tests Participants will have a baseline visit. This will include some repeats of the screening tests. They may also have leukapheresis: Blood will be taken from a needle in one arm and passed through a machine that separates out the white blood cells. The rest of the blood will be returned through a needle in the other arm. Participants will receive 8 doses of belimumab through IV: A needle will insert a thin plastic tube into an arm vein. Belimumab will be given through the IV line. The first 3 doses will be given every 2 weeks. The other 5 will be given once every 4 weeks. Participants will have a physical exam and blood and urine tests at each dosing visit. They will be monitored for up to 4 hours after the infusion. Participants will have 3 follow-up visits, at around 8, 16, and 24 weeks after the last dose of belimumab. They will have a physical exam and blood and urine tests. Once they finish this protocol and they will continue to be followed under 09-I-0102 (EPIC study). Read Less

The goal of this study is to identify a safe and tolerated dose of the orally administered KIF18A inhibitor ATX-295. In addition, this study will evaluate the pharmacokinetics, pharmacodynamics and preliminary antitumor activity of ATX-295 in patients with advanced solid tumors and ovarian cancer. Read Less

This phase I/II trial studies the safety, side effects and best dose of M3814 and to see how well it works when given together with radiation therapy in treating patients with pancreatic cancer that has spread to nearby tissue or lymph nodes (locally advanced). M3814 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving M3814 and hypofractionated radiation therapy together may be safe, tolerable and/or more effective than radiation therapy alone in treating patients with locally advanced pancreatic cancer. Read Less

The objective of the study is to conduct a randomized controlled trial of Cognitive Behavioral Therapy for Insomnia (CBT-I) in a sample of active-duty sailors with a history of traumatic brain injury (TBI). The investigators will test the impact of CBT-I on insomnia symptoms as well as post-concussive symptoms, psychological symptoms, and neurocognitive functioning in comparison to treatment as usual. The investigators will also compare the effectiveness of traditional in-person CBT-I and CBT-I delivered via a clinician-supervised digital health platform, Clinician Operated Assistive Sleep Technology (COAST) in comparison to treatment as usual on symptoms of insomnia, post-concussive symptoms, neurocognitive functioning, and psychological health. Participants will be assessed at baseline, post-treatment, and 3 months later. Read Less

This trial collects multiple tissue and blood samples, along with medical information, from cancer patients. The "Cancer Moonshot Biobank" is a longitudinal study. This means it collects and stores samples and information over time, throughout the course of a patient's cancer treatment. By looking at samples and information collected from the same people over time, researchers hope to better understand how cancer changes over time and over the course of medical treatments. Read Less

The goal of this clinical trial is to understand how well a culturally-specific "prebunking" video can improve vaccine information literacy and vaccine confidence among individuals in the Nusantara sociocultural sphere. The investigators hypothesize the individuals who watch the co-created "prebunking" intervention video will have improved vaccine literacy skills and vaccine confidence compared to individuals who watch a video about safe medication disposal. Read Less