Clinical trials

Background: Malaria is a serious disease caused by parasites spread by mosquitoes. To better diagnose and treat malaria, researchers need to learn more about where the parasites go when they enter a person's body. They want to see if they can locate the malaria parasites in the body using imaging scans. Objective: To learn whether imaging scans can locate parasites in people with malaria. Eligibility: Healthy people aged 18 to 54 years. They must be enrolled in protocol IRB001970 or IRB002627 for controlled malaria infection. Design: Participants will be screened. They will have blood drawn and a physical exam, including an abdominal exam to check the size of their spleen. Participants for this study will have 2 or 3 positron emission tomography/computed tomography (PET/CT) scans: The first will be about 3 days before they are deliberately infected with malaria for a different study. The second will be about 13 days later, while they have the disease. The third scan is optional; it will be done about 3 and 1/2 weeks after the second scan. For each scan, participants will receive a radioactive tracer called fluorodeoxyglucose (FDG). FDG will be injected through a tube inserted into a vein. They will lie on a table that slides through a doughnut-shaped machine. PET/CT uses x-rays to create images of the inside of the body. All participants will have a follow-up visit about 3 and 1/2 weeks after the second scan. The blood draw and physical exam will be repeated. This visit may be combined with the third scan for those who choose it.

Background: PDE4D is a protein found in the brain. It helps control chemical signals that affect mood, memory, and thinking. Problems with PDE4D may play a role in depression and Alzheimer's disease. Being able to measure PDE4D levels in the body would help doctors identify and manage these diseases. Researchers want to find out if a new tracer (a radioactive substance injected during imaging scans) can help them see PDE4D in people more effectively. Objective: To test a new tracer (\[11C\]JMJ-129-d2) during imaging scans of the brain and body in healthy people. Eligibility: Healthy people aged 18 years and older. They must have been screened under protocols 01M0254 or 17M0181. Design: All participants will give samples of blood and urine. They will have a test of their heart function. A plastic tube will be inserted into a vein in their arm; the new tracer will be given through this tube. Some participants will have 1 positron emission tomography (PET)/computed tomography (CT) scan of their whole body. They will lie on a padded bed that slides into a doughnut-shaped machine; the machine uses x-rays to create images of the inside of the body. Some participants will have 1 or 2 PET/CT scans of their brain only. Their head will be supported to keep it still during the scan. They will also have a magnetic resonance imaging (MRI) scan of the brain. MRI uses magnetic fields to capture images of the inside of the body. The MRI scan may require a second visit. All participants will receive a follow-up call to check on their well-being 1 to 3 business days after their scans.

This clinical trial will study an investigational seasonal influenza vaccine in adults 18 to 64 years of age. The vaccine is based on messenger ribonucleic acid, also called mRNA. The main goals of the study are to learn how well the vaccine helps the body make an immune response against influenza and what medical problems participants may have after vaccination. Researchers will also compare immune responses in adults 18 to 64 years of age from this study, with immune responses in adults 65 years of age and older from another study. Participants will receive 1 injection into the upper arm muscle and will be followed for about 6 months.

Chronic low back pain (cLBP) is a leading cause of disability, with socioeconomically disadvantaged populations experiencing worse outcomes and lower rates of treatment initiation for evidence-based pain psychology services. Participant engagement strategies such as shared decision-making (SDM) and motivational interviewing (MI) have shown promise in improving treatment uptake, but no study has examined whether integrating these approaches into a pain psychology evaluation can improve engagement among socioeconomically disadvantaged participants or offered participants a structured choice between cognitive behavioral therapy (CBT) and emotional awareness and expression therapy (EAET), presented to participants as Pain and Emotion Reprocessing Therapy (PERT). The Empowering Pain Psychology Access and Collaboration (EPPAC) intervention, a brief, psychologist-led engagement strategy combining SDM and MI within a standard pain psychology evaluation, was developed to address this gap.

Background: Rheumatic diseases can affect the joints, ligaments, tendons, bones, muscles, and skin. They can also cause inflammation, damage body tissues, and change nerve signals in the brain. This can lead to ongoing pain that interferes with daily life. Researchers want to know more about how pain affects the lives of those with rheumatic diseases. Objective: To learn how the body and brain experience pain in people with and without rheumatic diseases. Eligibility: People aged 9 to 85 years with a diagnosed or suspected rheumatic disease and ongoing pain. They must be enrolled in protocols 01-AR-0227, 94-AR-0066, or 11-AR-0223. Healthy volunteers are also needed. Design: All participants will have an initial visit and may have up to 5 follow-up clinic visits spaced about 6 months apart. Each visit may last 3 to 4 hours. Patients with rheumatic diseases may have up to 2 more visits if they have a disease flare-up. All participants will have these procedures at each visit: Bedside quantitative sensory testing (B-QST): The participant's body will be touched with various probes: a cotton tip, a tuning fork, an ice-cold tuning fork, a heat probe, a device that applies pressure, and a probe with a sharp tip. These probes will not cause injury. Participants will describe how the touches feel and rate the intensity on a scale of 1 to 10. Questionnaires: They will rate their overall health, quality of life, and any disease activity. Research blood: Blood will be collected during the visits. Some blood will be used for how environmental factors affect our genes. Physical exam and History review: They will provide information about their medical history and physical exam will be performed by a clinician.

This feasibility study will evaluate delivery of the Supporting Play Exploration and Early Development Intervention after neonatal intensive care unit discharge for very preterm infants and their families. Parent-preterm infant dyads will be assigned to homebased SPEEDI, telehealth SPEEDI, or a control group. SPEEDI is an early developmental intervention focused on supporting parent confidence, interpretation of infant behavioral cues, and parent-infant relationship building through developmentally appropriate play. The study will assess feasibility of initiating SPEEDI 1 to 5 days after NICU discharge, including recruitment, retention, session attendance, activity log completion, intervention adherence, and delivery differences between homebased and telehealth SPEEDI. Family experiences and provider perspectives on strengths and barriers to SPEEDI implementation will also be evaluated.

The purpose of this study is to learn about the safety, tolerability, and immune response of the RSVpreF vaccine in healthy older adults. Participants will take part in this study for about 6 months. The study will include people in China and the United States. In China, participants will receive either RSVpreF or placebo. A placebo is a dummy vaccine with no active ingredient, but it looks just like the vaccine being studied. In the United States, all participants will receive RSVpreF. Researchers will check for any reactions. They will also check blood test results to learn how the body responds to the vaccine. The main questions the study aims to answer are: * What local reactions and systemic events (body-wide symptoms) do participants have after a RSVpreF vaccination? * What medical problems do participants have after a RSVpreF vaccination? * Researchers will compare antibody levels from blood tests between the China cohort and the US cohort. An antibody is a substance in the body that try to fight off an infection or foreign substance. Participants will: * Have a screening visit to make sure they qualify for the study (participants in China will have this visit before the day of vaccination) * Receive the RSVpreF vaccination (or a placebo injection if in the China cohort) once at Visit 1. * Have a telephone or clinic visit 1 week later to assess local reactions and systemic events. * Have a clinic visit a month after vaccination for a checkup and tests. * Have a telephone or clinic visit 6 months after vaccination for a health check. * Have a blood test at screening (if in the China cohort only), on the day of vaccination and 1 month after vaccination.

This is an early study of a catheter-based minimally invasive procedure called SESAME to slice thick heart muscle as described below. Excessively-thick heart muscle can cause serious heart disease, especially heart failure with preserved ejection fraction, which causes shortness of breath and heart failure symptoms such as edema (swelling) and pulmonary congestion (lung water). Specific circumstances of excessively-thick heart muscle can block outflow of blood from the main heart pumping chamber (left ventricle). We developed a catheter technique called SESAME (SEptal Scoring Along Midline Endocardium) to slice the excessively-thick heart muscle causing such problems. SESAME can be used in patients who have symptoms related to excessively-thick heart muscle in a part of the heart that restricts blood ejection from the heart; the problem is called "left ventricular outflow tract obstruction (LVOTO)." One group of patients who might benefit from SESAME suffer from a common inherited heart muscle disease called "hypertrophic cardiomyopathy (HCM)." Patients with HCM and symptoms from LVOTO can be treated with medications, open heart surgery, or catheter-based destruction of heart muscle in "alcohol septal ablation." If these treatments fail or are not suitable, then SESAME may be an option, because it resembles surgery treatment without open heart surgery. Other groups of patients that might benefit are those with heart valve diseases, of the mitral or of the aortic valve, or both, along with excessively-thick heart muscle. These patients may be poor candidates for standard surgical valve repair or replacement because of high risk of complications or death. Such patients might be eligible for non-surgical transcatheter mitral valve replacement, either standard or unapproved ("off-label") or research ("investigational"), but are poor candidates because of risk of LVOTO. Moreover, about half have LVOTO making heart valve symptoms worse. Treating the LVOTO alone may improve symptoms enough that heart valve treatment can be delayed or avoided. This is a sponsor-investigator IDE study of SESAME performed at a small number of centers that have adopted the technique in the practice of medicine, in order better to characterize how well it works and whether it is safe. Participating centers already perform SESAME in the practice of medicine using improvised, off-label devices. This protocol allows prospective oversight, standardized technique constraints, central imaging review, independent monitoring, and formal safety adjudication. In addition, the investigational protocol does not function as the gatekeeper for access to SESAME. The investigators are not affiliated with the guidewire manufacturer and do not seek marketing approval or clearance for SESAME.

Background: Cerebrospinal fluid (CSF) is the liquid that fills the space around the brain and spinal cord. Researchers do not fully understand how CSF flows and drains around the brain. They want to test a tracer (gadobutrol)-a special dye injected into the CSF-to find out if it is safe to use and can help them get clearer pictures of the CSF during magnetic resonance imaging (MRI) scans of the brain. Objective: To test gadobutrol in the CSF during MRI scans of healthy people. Eligibility: Healthy volunteers aged 18 years and older. They must be screened under NIH protocol 89N0045. Design: Participants will check into the clinic for a 3-day stay. They will have a lumbar puncture: An area on their lower back will be numbed. A thin needle will be inserted into the space around the spinal cord. A sample of CSF will be taken for research. Then a low dose of gadobutrol will be injected into the CSF. Participants will have 4 or 5 MRI scans of the brain-30 minutes, 4 hours, 8 hours (this one is optional), 24 hours, and 48 hours after receiving the gadobutrol. For the scan, they will lie on a table that slides into a cylinder. Special padding will be used to hold their head still. The MRI uses magnetic fields to create images of the inside of the body. Blood and urine samples will also be collected at each scan. Participants will return for an additional MRI 1 week after they leave the clinic. They will have 2 follow-up phone calls 4 and 12 weeks after the start of the study.

Background: Chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) are diseases in which the body makes too many white blood cells that do not work properly. Because white cells play a role in immune function, people with CLL/SLL may be at greater risk of infections. CLL/SLL can be controlled with drugs, but many people develop resistance, and the treatments stop working. Objective: To test a new drug (nemtabrutinib) in people with CLL/SLL. Eligibility: People aged 18 years or older with CLL/SLL that persists despite treatment. Design: Participants will be screened. They will have imaging scans, blood and urine tests, and a test of their heart function. They will have a bone marrow biopsy: a sample of tissue and fluids will be drawn from inside their hip bone. They may also have a sample cut from a swollen lymph node, if one is safe to access. Nemtabrutinib is a tablet taken by mouth. Participants will take the drug once a day at home in 4-week cycles. They will have clinic visits at least every 4 weeks for the first 6 months and then every 3 months after that. Biopsies, imaging exams, and other tests may be repeated at these visits. Participants may also undergo lymphapheresis: Blood will be drawn from a tube inserted into a vein. The blood will pass through a machine that separates out cancer and immune cells. The remaining blood will be returned to the body through a different tube. Participants may stay in the study as long as the drug is helping them.

This prospective, single-center, first-in-indication feasibility study will evaluate the safety and preliminary effectiveness of spinal cord stimulation (SCS) for the treatment of severe, treatment-refractory primary Restless Legs Syndrome (RLS). Participants will undergo implantation of the Saluda Medical Evoke® Spinal Cord Stimulation System and will be followed for 24 months with clinical, neurophysiological, and patient-reported outcome assessments.

The purpose of this trial is to evaluate how well petosemtamab in combination with chemotherapy works against colorectal cancer that has recurred after previous treatment and that cannot be safely removed by surgery or has spread to other parts of the body. Participants will receive either petosemtamab + doctor's choice of chemotherapy (mFOLFOX6 or FOLFIRI) or doctor's choice of standard-of-care (SOC) cetuximab or bevacizumab + chemotherapy (mFOLFOX6 or FOLFIRI). No participants will be given placebo. The treatment duration will be different for every participant. If a participant's cancer stays the same or gets better, and there are not any serious problems, participants can keep getting study treatment for as long as the study is open. Participants will be asked to attend 2 visits at the study clinic for each cycle (duration of cycle is 4 weeks). During visits, there will be various tests (such as blood draws) and procedures (such as imaging) to monitor whether the study treatment is safe and effective. The overall study duration (including screening, treatment, and follow-up) will be different for every participant.

This first-in-human pilot study will test an investigational miniature breathing device called the Hope inVent. The device is a small, single-use, in-line respirator that connects to a breathing tube and uses compressed oxygen to help move air in and out of the lungs. It has no moving parts and is designed to provide short-term breathing support in situations where standard ventilators may not be available, such as emergencies, disasters, battlefield settings, transport, or ventilator shortages. The study will enroll up to 5 brain-dead organ donors who are already receiving mechanical ventilation at the Gift of Life Donor Care Center at the Hospital of the University of Pennsylvania. Donors will only be included after authorization for organ donation and research has been obtained through standard procedures. Donors who may donate lungs or who have significant lung disease will not be included. During the study, investigators will briefly replace the standard ventilator with the Hope inVent device for up to 15 minutes. The standard ventilator will remain immediately available, and the donor will be continuously monitored by the clinical and research teams. Investigators will measure whether the device can maintain acceptable breathing measures, including oxygen level and carbon dioxide level. They will also record breathing pressures and tidal volume, which is the amount of air delivered with each breath. If the device does not perform as expected or if any safety concern occurs, the donor will be returned immediately to the standard ventilator. There is no direct benefit to the organ donor. Information from this study may help determine whether this type of simple, low-cost breathing device could be useful for future patients who need emergency or short-term ventilator support when standard ventilators are not available.

Background: Pediatric disruptive behavior disorders (DBDs) are characterized by severe irritability, anger, and temper outbursts. The primary way to treat children with DBDs is parent management training (PMT). PMT teaches parents how to reward desired behaviors and not to reward undesired ones. Researchers want to find out if a smartphone app can help parents apply these skills more effectively. Objective: To test a smartphone app to enhance PMT. Eligibility: Children aged 8 to 13 years with DBDs. A parent or guardian is also needed. Design: Parents will have 12 weekly sessions of PMT. PMT teaches them how to manage their child s mood and behaviors. Parents will learn to actively ignore, praise, set limits, and handle temper outbursts. PMT can be either in person or via video. Sessions last 30 to 60 minutes. They will be video and audio recorded. Parents will be divided into 2 groups. Only 1 group will download a smartphone app. The app helps parents practice PMT skills. It offers videos, a resource library, and alerts when a child may be at risk for various behaviors. All parents will be prompted every day to answer questions about their child s mood and their own behavior. These will continue until 12 weeks after their last PMT session. Children will also answer questions on their phone daily for 1 week at a time. They will do this on 3 different weeks, each about 2 months apart. They will also have check-ins by phone every 2 weeks for up to 6 months. Parents will have follow-up calls 3, 6, and 12 months after they finish PMT.

Background: Recurrent respiratory papillomatosis (RRP) is a rare disease that causes wart-like growths called papillomas to grow in the airway, most often in the voice box, windpipe, or lungs. These growths can make it hard to speak or breathe. Surgery can remove the papillomas, but they often come back. In some cases, they can become cancerous. Objective: This study istesting whether two treatments used together (PRGN-2012, a vaccine-based treatment and bevacizumab, a drug that affects blood vessel growth) can help control RRP and reduce the chance that papillomas will grow back. Eligibility: Adults aged 18 years and older may be able to join the study if they have RRP and meet certain treatment history requirements. This may include people who have previously received PRGN-2012 or bevacizumab, or people who have needed more than 2 surgeries to remove papillomas. Design: Before starting treatment, participants will have screening tests to make sure the study is safe for them. These tests may include a physical exam with blood and urine tests, heart function testing, imaging scans, and an endoscopy. During an endoscopy, a thin, flexible tube with a small camera will look at the inside of the nose, throat, voice box, and upper windpipe. Participants will receive study treatment during 7 clinic visits over about 6 months. Bevacizumab is given through a vein amd PRGEN-2012 is given as an injection under the skin of the arm or leg. Participants may receive 1 or both drugs at each visit. After completing treatmen, participants will return for 4 follow-up visits over 1 year. These visits may include repeat imaging, blood and urine tests, and other exams. After that, the study team will contact participantsby phone or email every 3 months for 2 years. If their RRP gets worse during the follow-up period, they may be able to receive a second course of treatment using the same schedule....

The goal of this clinical trial is to learn whether guanfacine or cromolyn sodium can improve symptoms and physical functioning in adults with Postural Orthostatic Tachycardia Syndrome (POTS). Both medications are FDA-approved for other conditions but are investigational for the treatment of POTS. The main questions this study aims to answer are: Does treatment with guanfacine or cromolyn sodium improve physical functioning in adults with POTS compared with placebo? Does treatment with guanfacine or cromolyn sodium improve fatigue, cognitive function ("brain fog"), gastrointestinal symptoms, and overall symptom burden in adults with POTS? Researchers will compare guanfacine, cromolyn sodium, and placebo to determine whether either active treatment provides greater improvement in symptoms and physical functioning than placebo. Participants will: Be randomly assigned to receive guanfacine, cromolyn sodium, and placebo during separate 4-week treatment periods in a randomized, double-blind crossover study. Continue standard non-drug POTS management, including recommendations for fluid and salt intake, exercise, compression garments, and other lifestyle measures. Complete questionnaires that measure physical function, fatigue, cognitive symptoms, gastrointestinal symptoms, and overall health throughout the study. Attend scheduled study visits for safety monitoring and assessment of study outcomes. Provide blood, urine, and sputum samples so researchers can evaluate biomarkers related to POTS and better understand how these treatments may work.

Background: Vision is vital for many of our daily activities. Researchers want to learn more about how we aim our eyes (that is, what images, such as faces, immediately attract our attention) and how we direct our attention (that is, what we see and what we ignore). Objective: To study how healthy adults process and respond to visual images. Eligibility: Healthy people aged 18 years with no vision problems. Design: Participants will have 5 to 10 clinic visits over 2 to 4 months. Some participants may have up to 25 visits. Each visit lasts about 1 hour. Participants will be screened. They will answer questions about their medical and eye history. They will have a standard eye exam; eye drops will be used to dilate the pupils. (They may skip this exam if they have had an eye exam at the NIH within the past year.) Participants will perform eye movement tests. They will sit in front of a computer and view images that appear on the screen. They may be asked to respond to what they see by speaking, moving their hands, looking in a certain direction, or pushing a button. Their eye movements will be tracked. For some tests, participants heads may be held steady using a chinrest and head strap. For some tests, they may wear a cap fitted with cameras that use invisible lights in front of their eyes.

Background: About 180,000 of the people in US prisons are over 55 years old. Aging people often cannot make medical decisions on their own. People who cannot make their own decisions must rely on a "surrogate." A surrogate is someone who helps the person's doctor make decisions for them. Researchers want to conduct a survey to ask people in prison who they would like to be their surrogates. But first, they need to find out if their survey questions are clear and easy to understand. Objective: To get imprisoned people's feedback on survey questions about surrogate decision making. Eligibility: People currently imprisoned in a US facility with access to Edovo. They must be able to read and write in English. Design: Participants will answer 26 survey questions. The questions will be on the Edovo Learn software platform. After each question, they will be asked: "Was this question clear? If not, please explain in the box below what you found unclear. Also, if you have any suggestions for how we might make the question clearer, please include them." Participants will be asked to imagine themselves in a situation where they cannot make their own medical decisions. They may skip questions or stop the survey if they want. No information that identifies them will be collected. The survey will take about 15 minutes.

The purpose of this study is to assess the effect of renal impairment on the pharmacokinetics (PK) and safety of RO7795081, following a single oral dose in participants with renal impairment compared with participants with normal renal function. In Part 1, participants with normal renal function and participants with severe renal impairment or kidney failure not receiving dialysis will receive RO7795081. Part 2 is optional and will be conducted based on the results of Part 1. If Part 2 is implemented, additional participants with normal renal function and participants with mild or moderate renal impairment may be enrolled to receive RO7795081.

Background: Sepsis is an illness that occurs when the body s immune system runs out of control. This can damage organs. Sepsis causes an estimated 1 in 5 deaths worldwide. In this natural history study, researchers want to learn more about how the immune system changes during sepsis. They hope this knowledge will help them find better ways to treat sepsis. Objective: To understand how sepsis affects the body over time. Eligibility People aged 18 years and older admitted to INOVA Fairfax Hospital in Virginia and who have sepsis. Design: Researchers will collect data from participants medical records. Participants will have blood drawn at least 5 times while they are in the hospital. Blood may be collected for up to 30 days, if they remain in the hospital that long. The blood will be taken from access lines that are already in place. Some blood draws will be optional. Participants may opt to have up to 3 tests of their heart function while they are in the hospital. Some participants may have a sample of fluid collected from their lungs. Participants will have a follow-up visit about 90 days after they join the study. This visit will be by phone call if they have left the hospital. They will fill out a questionnaire. They will answer questions about their health and how they feel. The call will last about 30 minutes.

The purpose of the study is to investigate the efficacy of galvokimig versus placebo in the time to the first acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in study participants with moderate-to-severe COPD with chronic bronchitis.

Background: Normal aging, as well as dementias such as Alzheimer s disease, can cause changes in the brain that affect memory, attention, and thinking. Researchers want to know if regular mental tasks (cognitive training) can improve brain function in older adults. They also want to know if psilocybin, a compound found in certain mushrooms, can further support improved brain function. Objective: To learn how regular cognitive training, with or without psilocybin, can improve brain health in older adults. Eligibility: People aged 65 years and older with mild cognitive impairment or early-stage Alzheimer s disease. Healthy older adults with normal cognition are also needed. Design: Participants will be screened. They will have a test of their heart function and an imaging scan. They will have mental health screening and tests of their thinking and memory. They will practice brain-training tasks on a tablet. Participants will be divided into 2 groups: 1 will have cognitive training plus psilocybin; 1 will have cognitive training only. Those having cognitive training only will have 5 or 6 clinic visits. They will take the tablet home to practice brain training daily. They will wear a device to measure brain waves as they sleep; they may have 1 overnight stay in the clinic, or they may wear the device at home. Imaging scans and other tests will be repeated at each visit. Those taking psilocybin will have up to 9 clinic visits. In addition to the visits for cognitive training, they will take 1 psilocybin capsule by mouth 2 weeks apart (the second dose is optional). They will remain in the clinic for 24 hours after each dose.

Background: Obesity is known to lead to diseases such as diabetes and high cholesterol (or fats) in the blood (hyperlipidemia). But no one knows why. Researchers think that high levels of fat in the blood may block important nutrients, such as vitamin E, from reaching places they are needed in the body. Objective: To learn how high-fat meals affect levels of vitamin E in the blood. Eligibility: People aged 18 to 65 with high blood fat levels. Healthy volunteers are also needed. Design: Participants will have 3 or 4 clinic visits in 3 months. The last visit will require them to stay in the clinic for 2 nights. Participants will be screened. They will have a physical exam and blood tests. After this visit, all participants must stop taking any dietary supplements. Those who use them must also stop taking any drugs to lower their blood sugar and blood fats. These participants will have an extra visit for blood tests after 60 days. The next visit will include 2 imaging scans: Magnetic resonance imaging (MRI) of the abdomen. This scan will check for fat in the liver. Dual-energy X-ray absorptiometry (DEXA). This scan measures the levels of body fat. On day 1 of the clinic stay, participants will have 2 set meals, with nothing but water after 10 pm. On day 2, they will drink high-fat shakes at 9am, 1pm, and 5pm. They will have blood draws every 30 minutes for the first hour, every hour the next 16 hours, and then every 2 hours until 7 am. The blood will be taken from a tube inserted into a vein and left in place for the day. On day 3, they will go home.

Background: Cancers that begin in the colon, adrenal glands, or bile ducts may spread to the liver. These liver tumors are often treated using a hepatic artery infusion (HAI) pump. The HAI pump is installed in the artery that goes to the liver; drugs are administered directly to the liver through this pump. But these tumors often return after treatment. Carfilzomib (CFZ) is a drug approved to treat another kind of cancer. Researchers want to find out if this drug may be helpful when administered through the HAI pump directly to the liver for people with colon, adrenal glands, or bile duct cancer that has spread to the liver. Objective: To test the safety of carfilzomib (CFZ) delivered via a hepatic artery infusion (HAI) pump directly to the liver in people with cancer in their liver. Eligibility: People aged 18 years or older with cancers of the colon, adrenal glands, or bile ducts that spread to the liver and persist after treatment. They must have a functioning hepatic artery infusion (HAI) pump in place from previous treatment of HAI pump therapy. Design: Participants will be screened. They will have a physical exam, blood tests, imaging scans, and a test of their heart function. They will also have a test to show how the blood flows through their liver: A radioactive substance will be injected into a vein, and a special camera will take pictures of the blood flow for up to 1 hour. Participants will receive the study drug for about 6 months. They will visit the clinic once a week. Their HAI pump will be filled with the drug at each visit; the drug will slowly drain from the pump into the liver. Blood tests and imaging scans will be repeated during the study. Participants will have follow-up visits 1 and 3 months after their last dose of study drug. An optional liver biopsy (tissue sample) for research purposes may be done before the study drug is given, and again (optional) within 28 days after first receiving the study drug. Individuals may participate in the study even if they do not agree to have the biopsies done. ...

This study is a screening evaluation for volunteers who are interested in participating in National Center for Complementary and Integrative Health (NCCIH) research studies about pain and related processes, such as emotion, mood, and decision-making. Screening may include review of medical history, physical exam, vital signs, questionnaires, blood and urine tests, and optional sensory testing to better understand pain and related symptoms. The purpose is to identify and characterize healthy volunteers and people with pain who may be eligible for future NCCIH research studies. This screening study does not test a treatment and has no formal hypothesis.