Clinical Research Directory

Early Metabolic Effects of Antiretroviral Drugs in Healthy volUnteers: a Phase 2 Randomized Study

Background: People with HIV take drugs to keep the amount of virus in their body low. One type of these drugs, called integrase strand transfer inhibitors (INSTIs), can cause weight gain over time. Weight gain can cause diabetes, heart disease, and other serious issues. Researchers want to understand how INSTIs cause weight changes. Objective: To characterize the change in plasma metabolite profile that 4 weeks of each treatment may induce in the absence of HIV infection Eligibility: Healthy people aged 18 to 55. Design: Participants will be screened in the outpatient clinic. They will have a physical exam and blood tests. They will have a nutritional assessment and tests of their heart function. Participants will be randomized to one of four oral treatments: Tenofovir Disoproxil Fumarate TDF/Viread, Tenovovir Alafenamide TAF/Vemlidy, Dolutegravir DTG/Tivicay, or both TAF and DTG taken together for 4 weeks. Participants will have a Day 0 visit for the Lead-In Baseline visit for an exam and blood tests and continuous glucose monitor placement. Participants will return in 2wks or Day 14/Wk 2 for a DEXA (dual-energy X-ray absorptiometry). DEXA is a kind of X-ray that measures body fat and bone density. Optional adiopse (fat) tissue biopsy in the abdomen, and optional microbiome specimen collections. Continuous glucose monitor changed. Oral once a day dose medication will be started with education. Participants will return in 2wks or Day 28/Wk 4 for exam, labs, and continuous glucose monitor changed. Participants will return in 2wks or Day 42/Wk 6 for final exam, labs, repeat DEXA scan, repeat adipose tissue biopsy, and microbiome specimen collections.

Evaluation of the Clinical Spectrum of Diabetes and Obesity in Youth and Adults

Background: Diabetes and obesity are chronic diseases. They can affect blood flow and how the body processes nutrients, and complications over time can lead to early death. Diabetes can affect children as well as adults, but the disease seems to be more severe and to progress faster when it appears in younger people. Researchers want to understand more about how diabetes and obesity develop and change over time. Objective: To collect data and samples regularly from people with obesity and diabetes. Eligibility: People aged 8 to 65 years. They must be overweight or obese; or have high blood sugar; or have problems with how their body uses food for energy. Design: Participants will have additional procedures during routine care visits at the NIH clinic. Data collected for the study will include the following: Information from the participant s medical chart will be kept for research. Questionnaires will ask about participant s eating habits, feelings, sleep, and substance use. They will take 30 to 60 minutes. Care providers will address any issues revealed in these surveys. Blood, saliva, urine, and stool samples will be collected. Samples may be used for genetic tests. Data and samples will be kept for future research. Participants may remain in the study up to 30 years.

Stem Cell Transplantation for Participants With Germline RUNX1 Associated Blood Cancers

Background: Some blood cancers can be caused by germline variants (changes) in a person s RUNX1 gene. Germline variants are genetic inherited changes a person is born with. Stem cell transplants are used to treat many diseases including blood cancers. Stem cell transplantation for patients with germline RUNX1 mutation driven blood cancers is standard of care and available in most major medical centers. The difference with this transplantation protocol is that it is prospective, only available to participants with germline RUNX1 variants and designed to determine the extent to which tailoring chemotherapy and supportive care medication doses for each individual patient may improve outcomes compared to data derived from retrospective transplantation protocols for patients with RUNX1 varinats which is less accurate. Objective: The primary objective of this protocol is to determine how tailored doses of chemotherapy and supportive care medications may improve disease free survival as compared to historical/expected disease free survival. Eligibility: People aged 4 to 70 years with blood cancer caused by a RUNX1 gene mutation. Other participants are also needed: (1) stem cell donors; (2) relatives who do not have a mutation in the RUNX1 gene; and (3) healthy volunteers. Design: Participants with blood cancer will be screened during approximately 1-3 months before transplatation. They will have blood tests and tests of their heart and lung function. A sample of bone marrow may be taken. A flexible tube (central line) will be inserted into a vein in participants chest or lower neck. This line will remain in place during the hospitalization and be used to draw blood and administer drugs. These lines are almost always transitioned to a peripherally inserted central catheter (PICC) line at the time of hospital discharge. Participants will be inpatient for 4 to 5 weeks. They will receive drugs to prepare their body for the stem cell transplant. Some may also receive radiation treatment. Other tests will include imaging scans. The stem cell transplant will be given through the central line. After discharge from the clinic, participants will have follow-up visits at least once per week for approximately 100 days. Then they will have follow-up clinic visits for 3 years. Donors, relatives, and healthy volunteers may provide samples of blood, stool, and saliva. Adults may also opt to provide samples of skin and bone marrow.

Osimertinib With or Without Bevacizumab as Initial Treatment for Patients With EGFR-Mutant Lung Cancer

This phase III trial compares the effect of bevacizumab and osimertinib combination vs. osimertinib alone for the treatment of non-small cell lung cancer that has spread outside of the lungs (stage IIIB-IV) and has a change (mutation) in a gene called EGFR. The EGFR protein is involved in cell signaling pathways that control cell division and survival. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving osimertinib with bevacizumab may control cancer for longer and help patients live longer as compared to osimertinib alone.

Evaluating the Safety and Tolerability of Baricitinib in Patients With Job Syndrome With Lupus-Like Disease and/or Atopic Dermatitis

Background: Autosomal dominant hyper-IgE syndrome (HIES), also called Job syndrome, is a genetic disorder that affects the immune system. It can cause skin and lung infections and problems with blood vessels, connective tissues, and bones. People with HIES often have lupus-like disease or atopic dermatitis (skin rash). Researchers want to know if a drug approved to treat other immune system diseases (baricitinib) can help people with HIES. Objective: To test baricitinib in people with HIES with lupus-like disease or skin rash. Eligibility: People aged 12 years and older with HIES with lupus-like disease or skin rash. Design: Participants will have 5 clinic visits, 4 remote visits, and 2 phone visits in 9 months. Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of the speed and pressure of blood flow through their body: Blood pressure cuffs will be placed on each arm and leg; electrodes will be placed on the wrists and a microphone on the chest. The study has a 3-month lead-in period. Participants will not take the study drug during this time. They will continue with their usual medical care. They will have 2 phone calls with the study team. Baricitinib is a tablet taken by mouth. Participants will take 1 or 2 tablets by mouth every day for 6 months. They will start with a low dose and may increase to a higher dose. Blood and urine tests will be repeated during each study visit. Other tests may also be repeated during some visits. A skin sample may also be taken....

Developing Transcranial Neuromodulation Protocols for Learning and Decision-Making

Background: People with substance use disorder (SUD) often have changes in brain function that can make it difficult to control drug-seeking behavior. These changes may heighten the urge to use drugs or lessen the desire to seek nondrug-related rewards. Researchers want to know how a technique called transcranial magnetic stimulation (TMS) may cause changes in brain activity that may help people with SUD. Objective: To test TMS in healthy volunteers. Eligibility: Healthy people aged 18 to 45 years who are right-handed. Design: Participants can volunteer for up to 5 different experiments. Each experiment requires 2 to 8 clinic visits. Each visit will last 3 to 7 hours. Some visits will include TMS. A coil will be placed on the participant s head. A brief electrical current will pass through the coil to create a magnetic field. Participants may feel a tapping or pulling sensation on the skin under the coil. They may feel a twitch in their face, neck, arm, or leg muscles. Participants may be asked to tense certain muscles during TMS. Some visits will include functional magnetic resonance imaging (fMRI) scans. Participants will lie on a bed that slides into a large tube. They will perform tasks on a computer inside the tube. The fMRI will show which parts of the brain are used during each task. Participants will perform tasks on a computer. Some tasks may be done at a desk as well as during TMS and fMRI. Participants may look at images, listen to sounds, smell odors, or taste flavored liquids. Their vital signs may be monitored and their eye movements may be tracked during tasks.

Prevalence and Development of Liver Dysfunction in Hematopoietic Stem Cell Transplant

Background: Hematopoietic stem cell transplant (HSCT) is a common treatment for many cancers and other illnesses. But many people who have HSCT go on to develop liver dysfunction. Researchers want to know more about how and why this happens. In this natural history study, they will try to learn what factors lead to liver dysfunction; how underlying liver disease may affect the results of HSCT; and how HSCT may contribute to liver dysfunction. Objective: To understand the links between HSCT and liver dysfunction. Eligibility: Adults aged 18 years or older and children 3 to 17 years who are being evaluated for HSCT. Design: This study involves 11 visits in 4 years. Most visits will be in the first year. Before and after their HSCT, participants will undergo these tests: Physical exam, including blood tests and a test of heart function. Participants will provide stool samples. Liver biopsies. Samples of liver tissue will be removed. This may be done either by inserting a needle through the right side of the chest, or with a thin tube threaded to the liver from a vein in the neck. Adult participants will undergo this procedure 2 times: once before the HSCT and once about a year later. Imaging scans. Participants will lie on a bed that moves into either a cylinder or a donut-shaped machine. Ultrasound. Participants will lie still. A probe that uses sound waves will be slid over their skin to get pictures of the liver. Fibroscan exam. This is like an ultrasound that uses a special probe to measure the toughness of the liver. ...

Study of Preoperative Radiation Therapy in Participants With Resectable Recurrent Abdominal Adrenocortical Carcinoma

Background: Adrenocortical carcinoma (ACC) is a rare cancer of the adrenal glands. ACC often returns after tumors are removed with surgery. Less than 35% of people with ACC survive 5 years after diagnosis. Objective: To test a new type of external beam RT before surgery in people with ACC. Eligibility: People aged 18 years and older with ACC that came back after treatment but may be safely removed with surgery. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of their heart function. They will have imaging scans. A small sample of tumor tissue may be collected if one is not available. They will undergo laparoscopy: Small incisions will be made in the abdomen so that a thin tube with a light and camera can be inserted to view the organs. RT comes from a machine that aims radiation at tumors. Participants will receive preoperative RT in daily fractions over approximately 2-3 weeks, followed by a planned surgical resection about 4 weeks after the completion of RT. Visits will last 30 to 60 minutes. Participants will undergo surgery to remove their tumors about 4 weeks after they finish RT. They will stay in the hospital 1 to 3 weeks after surgery. Participants will have follow-up visits for 10 years after surgery.

Role of Theta Frequency Oscillations in Proactive and Reactive Control Processes in Youth With Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD)

Background: Attention deficit hyperactivity disorder (ADHD) is common in children. It can cause problems with attention and the ability to control actions and impulses. Obsessive compulsive disorder (OCD) is less common in children but not rare. It involves ongoing thoughts, urges, impulses, and repeated behaviors. Researchers want to study differences in brain activity between healthy children, those with ADHD, and those with OCD. Objective: To learn more about how the brain controls thinking and behavior. Eligibility: People aged 12 to 17 years with ADHD, OCD, or neither. Design: Participants will have 3 to 10 clinic visits in up to 1 year. Each visit will last 2 to 3 hours. Three visits are required: Behavioral. Participants will complete a computer task. Their mood, memory, attention, and thinking skills will be tested. EEG. Participants will undergo electroencephalography (EEG) to measure signals in their brain. Small electrodes will be placed on the scalp. A cap will be stretched over the head. Signals will be recorded while participants rest or do tasks on a computer. MRI. Participants will have a magnetic resonance imaging scan (MRI). They will lie on a table that rolls into a tube. The MRI will take pictures of their brain while they do tasks on a computer. Seven more visits are optional. These include 2 more EEG visits and 2 more MRI visits. Three will be magnetoencephalography (MEG) visits: MEG measures small magnetic field changes in the brain. A helmet with sensors will be placed on the head. Brain changes will be recorded while participants rest or do tasks on a computer.

Management and Leadership in Healthcare: Expectations, Conditions, Skills, and Reflections in a Leadership Program

This study follows first- and second-line healthcare managers who take part in an established leadership development program in a Swedish healthcare region. The study examines managers' expectations of the program and how they describe their skills and conditions for practicing management and leadership before, during, and after participation. It also explores their reflections on the program, including learning, new insights, application in everyday management practice, and conditions for taking part. Participants complete questionnaires before the program, immediately after it ends, and one year later. During the program, they record reflections in structured diaries. After the program, participants are invited to focus group interviews to discuss their experiences in greater depth. The questionnaire, diary, and interview findings will be combined to provide a broader understanding of managers' development and experiences of the program.

Experience and Management of Cancer Screening-Related Anxiety in Fanconi Anemia

Background: Fanconi anemia (FA) is a rare, inherited cancer syndrome. FA causes a range of physical issues. Children with FA may have abnormal features; these may include a small head and eyes and issues with their internal organs. Young adults have a much higher risk of cancer. To screen for these cancers, people with FA may need to pursue many visits with different doctors. This constant need for cancer screening may cause anxiety for people with FA. Objective: To learn more about anxiety related to cancer screenings in people with FA. Eligibility: Adults aged 18 years and older with FA. They must also be enrolled in FACSS. FACSS is a study that screens people with FA for cancer every year. Design: All data gathered for this study will occur during routine FACSS visits. No other visits are needed. An observer will be in the room during participants FACSS visits. The observer and participant will have a polite introduction. After that, the observer will not interact with participants in any way. The observer will note details about the participants, such as: * Body language. * Worries about screening. * Comments that suggest anxiety or depression. * Clinical environment, such as d(SqrRoot)(Copyright)cor and temperature. * Accessibility issues. These can include lights and noises as well as ease of traveling around the clinic center. * Evidence of social support, such as engaging in the FA community. * Challenges they ve had in FACSS. * Their motivation to participate in FACSS. * Relationship dynamics among clinic staff, participants, and their care partners. Data will also be collected from FACSS visit notes dating back to December 2024 and from participants medical records.

IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors

Background: Myeloid cells are a type of immune cell found in most tumors. Interleukin 12 (IL-12) is a protein the immune system makes that can help kill tumor cells. Researchers want to know if myeloid cells that have been genetically engineered to produce IL-12 (IL-12 GEMys) can attack cancer cells in solid tumors. Objective: To test IL-12 GEMys in people with cancer. Eligibility People aged 18 years and older with cancer that returned or failed to respond to treatment. Design: Participants will be screened. They will have a physical exam with blood tests. They will have tests of their heart and lung function. They will have imaging scans of their tumors. A sample of tumor tissue may be taken. Participants will undergo leukapheresis: Blood will be taken from the body through a needle inserted into a vein. The blood will pass through a machine that separates out stem cells. The remaining blood will be returned to the body through a different needle. The collected stem cells will be modified in a lab to create IL-12 GEMys. Participants will check in to the hospital. They will receive drugs for 5 days to prepare their body for the treatment. Then they will have their own IL-12 GEMys infused through a needle inserted into a vein. They will stay in the hospital until they are well enough to go home. This may be 7 to 14 days or longer. Some participants may receive a second treatment with IL-12 GEMys within 2 years after the first. Participants will have follow-up visits for about 5 years. These will include imaging scans and blood tests.

Natural History Study of Early Life Exposures in Agriculture (ELEA)

Study Description: ELEA is an observational cohort study that will collect exposure information and biospecimens from the adult children of the Agricultural Health Study (AHS) cohort (https://aghealth.nih.gov/about; Protocol OH93NCN013). The primary hypothesis is that early life exposures, particularly those found in the agricultural environment, are associated with cancer and other adverse health outcomes in childhood and early adulthood. Eligible individuals will be invited to complete an online questionnaire. After enrollment, study participants may be asked to donate biological and environmental samples. Participants will be followed for cancer and other disease endpoints. Data will be collected from North Carolina and Iowa health registries, disease specific databases, the National Death Index (NDI), North Carolina and Iowa state health registries, publicly available environmental datasets, discarded sample repository, and collection of available samples. Investigators will access data and biospecimens from the AHS protocol OH93NCN01 and link it to the ELEA population. In an earlier ELEA protocol (16CN095) the NCI SS IRB approved the protocol to perform linkages. That protocol was closed after the transition to the NIH IRB (per a NHSR determination), but the linkage work continued under the ELEA protocols that remained open with Westat and Iowa. Objectives: Primary: To investigate the effect of specific pesticides and other agricultural exposures and risk of cancer in children and adults. Secondary: To investigate the effect of non-agricultural exposures and the risk of cancer and other diseases in children and adults. Exploratory: Exploratory objectives include, but are not limited to, the examination of genetic and various molecular biomarkers in relation to childhood agricultural exposures. Endpoints: Primary: Incidence of Cancer Secondary: Incidence of diseases other than cancer, survival, and various molecular biomarkers. ...

RB001 Gene Therapy Study in Children With SHANK3-related Phelan-McDermid Syndrome (PMS)

This is a first in human, open-label, dose-escalation study to evaluate the safety, tolerability, and clinical activity of a single dose of RB001 administered via intracerebroventricular (ICV) injection in pediatric with SHANK3 related Phelan-McDermid Syndrome. Clinical data will be evaluated for safety, tolerability, and preliminary efficacy of RB001 in participants with SHANK3 related PMS.

A Study to Evaluate AZD7760 Safety and Pharmacokinetics in Healthy Adults (Phase I) and Adults With End-stage Kidney Disease on Hemodialysis With a Central Venous Catheter (Phase IIa)

The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of AZD7760 when given as an intravenous infusion to healthy participants (Phase I) or participants with end-stage kidney disease receiving hemodialysis through a central venous catheter (Phase IIa).

Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia

This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged \[R\]) or without a KMT2A gene rearrangement (KMT2A-germline \[G\]). 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. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs 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. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.

A Study of AZD3470, a PRMT5 Inhibitor, Given as Monotherapy and in Combination in Patients With MTAP Deficient Advanced/Metastatic Solid Tumors

This is a first time in human (FTiH) Phase I/IIa, open-label, multi-centre study of AZD3470 in participants with advanced or metastatic solid tumors with MTAP deficiency. The study consists of several study modules, evaluating the safety, tolerability, pharmacokinetic (PK), pharmacodynamics, and preliminary efficacy of AZD3470 as monotherapy or in combination with other anti-cancer agents.

Human Experimental Models of Pain (HEMP)

This pilot study will test an innovative way to establish how pain medicines provide analgesia in healthy adults. The study uses a group of short, controlled pain tests to look at different types of pain responses in the body. The main goal is to find out if this testing approach can show the pain-relieving effects of 2 medicines, pregabalin and naproxen versus placebo, and show how they provide relief of different types of pain. The study hypothesis is that this pain testing approach administered as a battery would be able to tell the difference between a medicine that works mainly in the brain and spinal cord (pregabalin) and a medicine that works mainly on inflammation in body tissues (naproxen). Up to 25 healthy adults will take part. Each participant will receive all 3 study treatments, pregabalin, naproxen, and placebo, administered in random order during separate study periods. The order will be assigned by chance. Neither the participant nor the study team will know which treatment is given at each visit. The study includes several experimental pain tests. These include: a heat and capsaicin skin test that causes short-term skin sensitivity, a UVB light test that causes a temporary sunburn-like sensitivity, and a cold pressor test, in which a hand is placed in very cold water for a short time. Participants will also have sensory testing to measure how they feel touch, pressure, pinprick, warmth, heat, and cold. Blood samples will be collected to measure study drug levels. Urine samples, vital signs, and other safety checks will also be done. Each treatment visit includes testing before and for several hours after taking the study drug. There will be a washout period of at least 48 hours between treatments. Total participation may last up to about 10 weeks. This study is not expected to provide direct medical benefit to participants. The information learned may help researchers improve early testing of future pain treatments....

Using Smartwatches to Monitor Smoking in Real-life Situations

Background: It is important to quickly identify when people are at risk of smoking. Most current methods rely on people reporting when they smoke or what makes them want to smoke. But this can be hard for people to do and may not always be accurate. Other methods use special gadgets to identify smoking movements, but these may not always work well in real life. We want to see if we can use devices available on the market such as smartwatches to identify signs in the body and hand movements that might indicate when someone is about to smoke, is currently smoking, or has just smoked. Objective: To record body signs and hand movements before, during, and after smoking in real-life and in a lab to see how they change when someone is craving cigarettes, while a person is smoking, and after a person has smoked. Eligibility: People who are 21 years or older and smoke, have no college degree or be currently enrolled in college, and are low-income earners. To participate in the study, participants have to pass a breath test that shows they smoke cigarettes and, for women, a urine test to show that they are not currently pregnant. Design: Participants will complete an eligibility survey to see if they qualify to be in the study. If they qualify, they will answer a brief baseline survey that includes questions about themselves, their health, and their smoking behavior. Participants will get a smartwatch to wear for 3 days at home, log each time they are about to smoke and have finished smoking, and answer a 5-question health survey via the app. They will get instructions on how to set up and wear the smartwatch. They will download a mobile application on their phone. The app will collect data from the smartwatch. Participants will then come to the lab but will be asked not to smoke or drink alcohol for at least 12 hours. They will have to take a breath test to show they have not smoked or had alcohol. They will also give a blood sample. In the lab, they will sit in a room where they will be hooked to devices that monitor their vitals such as heart rate and blood pressure for one hour. They will also wear a smartwatch on each hand. While they are in the smoking room, they will go through 3 different phases: (a) pre-smoking where they will be asked to stay seated for about 25 minutes, (b) smoking where they will be asked to smoke as many cigarettes of their choice as they want for about 10 to 15 minutes, (c) post-smoking where they will be asked to stay seated, not smoking, for about 25 minutes. They will answer a brief 10-minute health survey before and after the session. Participation will last for 3 days of home monitoring and 2 visits to the research clinic that last about 2 hours.

Cognitive and Affective Mechanisms Underlying an Olfactory Approach to Modify Cigarette Craving

The proposed study uses fMRI and behavioral measures in and outside the laboratory to investigate the neurobehavioral mechanisms underlying the impact of pleasant olfactory cues (OCs) on cigarette craving. The investigators plan to randomize 278 participants to a pleasant OC condition or an odor blank (neutral) condition and due to anticipated drop out expect to run 250 adult (half female) smokers, including both daily and nondaily smokers through the protocol. This study involves three visits. In the first visit, participants will complete a baseline breath carbon monoxide reading, a brief odor threshold test, and complete a series of self-report measures. In the next session, participants who are 8-hrs deprived of nicotine will undergo a 60-minute fMRI scan that will include structural, resting state, and task-based data collection. The fMRI task involves completing a series of tasks designed to index responses linked to key neural networks found to relate to addiction (e.g., reward processing, working memory). Participants will also be exposed to smoking cues to heighten craving and then depending on their condition (randomly assigned) will either receive a pleasant or neutral (odor blank) OC. In the third session, behavioral data will be collected to test the impact of either a pleasant or neutral OC on cigarette craving using self-reported urge and behavioral measures linked to craving. Finally, for pilot purposes designed to offer data for a subsequent clinical study (beyond this study), participants will additionally complete a 7-day ecological momentary assessment (EMA) protocol in which they will monitor cigarette craving and initial data will be collected outside the laboratory to evaluate the impact of OCs on naturally occurring craving. It is hypothesized that pleasant OCs will disrupt craving brain states and attenuate craving (as compared to neutral olfactory cues). Further, it is hypothesized that individual variation in neural responses to cognitive and affective tasks will reveal variation in mechanisms underlying pleasant OC craving reduction and that individual differences will moderate pleasant OC-induced craving relief. Finally, it is also expected that emotional responses to pleasant OCs will mediate the impact of OCs on craving and smoking-related processes.

Syk Inhibition in MItigating Lung Allograft Rejection (SIMILAR): A Trial to Evaluate the Safety and Tolerability of Fostamatinib in Lung Transplant Patients With Donor-Specific Antibodies

Background: People who have lung transplants often survive 6 or 7 years. But some people develop donor-specific antibodies (DSA) after their transplants; antibodies are proteins that attack foreign invaders in the body. Antibodies typically kill viruses and other agents that can cause disease. But when the antibodies attack a transplanted organ, they can cause the body to reject the new tissues. People who develop DSA after a transplant have a higher risk of death within 1 year. Objective: To test a drug called fostamatinib in people who develop DSA after a lung transplant. Eligibility: Adults aged 18 and older who developed DSA after a lung transplant. Design: Participants will continue with their standard care after a transplant. Fostamatinib is a pill taken by mouth. Some participants will take the study drug along with their standard care; others will take a placebo. A placebo is a pill that looks just like the real drug but contains no medicine. All participants will take 1 pill per day for 2 weeks. Then they will take 2 pills per day for the next 6 weeks. Participants will have clinic visits every 2 weeks while taking their pills. They will have a physical exam, with blood and urine tests, during each visit. If participants have fluid samples collected from their airways during their standard treatment, some extra fluid may be collected for this study. Participants will have a follow-up visit 4 weeks after they stop taking their pills.

Imaging- vs. Scalp-Targeted Accelerated TMS for Depression: The Number Needed to Scan Trial

Transcranial magnetic stimulation(TMS) is a non-invasive form of brain stimulation that is cleared by the United States Food and Drug Administration (FDA) for depression. Conventional TMS involves daily weekday treatments for 6-8 weeks. These treatments are targeted using each person's scalp measurements. With conventional TMS, approximately 50-55% of people show a 50% or more improvement in depressive symptoms (in other words, they "respond" to treatment). Studies are trying to make TMS work better and faster. A new form of TMS called accelerated TMS (aTMS) involves mutliple treatments a day. One specific aTMS protocol involves 10 treatments per day for 5 days. These treatments are targeted using each person's brain scan (magentic resonance imaging, MRI). With this specific aTMS protocol, approximately 70-90% of people show a 50% or more imporvement in depressive symptoms. While these results are exciting, scientists are not sure why this specific aTMS protocol works better than conventional TMS. It could be the dose and schedule of treatment, or it could be the MRI-based targeting. Answering this question is important because MRI-based targeting is expensive and difficult to do in many settings. This study aims to determine if MRI-based targeting is better than scalp-based targeting for aTMS for depression. In this study, everyone who enrolls and meets criteria will be randomly assigned to MRI- versus scalp-based aTMS targeting.

Effects of Meal Macronutrients on Postprandial Lipids

Background: Abnormal fats in the blood can lead to many problems, including heart disease. Researchers want to learn more about how eating meals with different levels of nutrients affects fats in the blood. Specifically, they want to study people with too much body fat, too little body fat, and a kidney problem called nephrotic syndrome. Objective: To learn more about how different types of foods affect fat levels in the blood. Eligibility: People aged 18 years or older with a health condition that affects how their body handles fats. Healthy volunteers are also needed. Design: Participants will have 2 overnight stays in the clinic within 6 months. At each visit, after staying overnight, they will eat a breakfast casserole. At 1 visit, breakfast will be a high-fat, low carbohydrate meal. At the other, it will be a high-carbohydrate, low-fat meal. Participants will have a tube inserted into a vein in their arm. They will have blood drawn via the tube 12 times in 8 hours: 2 times before they eat the breakfast and 10 times after. Participants will have other tests during their stays: * A resting metabolic test captures the air they exhale and measures how much energy they use at rest. * A dual energy X-ray absorptiometry (DXA) scan measures how much fat and muscle they have. * A Fibroscan is a special type of ultrasound of the liver. * A body surface scan uses lasers to measure the total area of the body. * A bioelectric impedance (BIS) exam measures how fast small electric currents move through their body. Participants may opt to have a third visit. At this visit, the breakfast will be high in protein....

Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease

Background: Inflammatory bowel disease (IBD) is a term used to describe disorders that cause long-term inflammation in the digestive tract. Symptoms include stomach pain, diarrhea, and bleeding. Crohn's disease and ulcerative colitis are the 2 main types of IBD. Researchers want to conduct a natural history study to learn more about whether genetic factors can cause IBD; how immune cells contribute to IBD; and how diet, drugs, and disease affect those cells. Objective: To better understand IBD over time. Eligibility: Adults aged 18 to 85 years with Crohn's disease, ulcerative colitis, or another IBD. Their healthy relatives are also needed. Design: Affected participants will have clinic visits every 6 months for 3 years. Once a year, they will have these procedures: A physical exam with blood and stool samples. Ultrasound of the abdomen. A wand will be rolled over the skin. It uses sound waves to capture images of the intestines. Magnetic resonance imaging (MRI) scan. They will lie on a table that slides into a tube. Magnetic fields will capture images of the intestines. Colonoscopy. A long, flexible tube with a video camera will be inserted into the rectum to view the entire colon. Up to 12 tissue samples may be taken. Upper endoscopy, for those with Crohn's disease. A long, thin tube with a camera will be inserted through the mouth and into the first part of the small intestine. Up to 12 small tissue samples may be taken. Questionnaires. Participants will answer questions about their disease and their diet. Midyear visits will include a physical exam, blood and stool collection, ultrasound, and questionnaires Healthy relatives will have 1 blood draw for genetic tests.