Clinical trials

Background: Many people in the United States are overweight or obese. This natural history study will look into how life events during childhood can impact eating behaviors and weight gain as adults. Objective: To explore how childhood experiences affect adult eating behaviors. Eligibility: Healthy people aged 18 to 60 years. Design: Participants will have 3 clinic visits. They will be screened with blood tests. They will answer questions about their alcohol and tobacco use. At the next visit, participants will undergo these activities: Parts of their body (such as waist, neck, and thighs) will be measured with a tape. They will have an imaging scan to find out how much body fat they have. They will start wearing a device like a wristwatch that measures their physical activity. They will wear this device for up to 10 days. They will wear a device on their upper arm or belly that measures blood glucose (sugar) levels. Participants will wear this for 7-10 days. They will answer questions about their education, childhood, and routines. They will receive a kit to collect a stool sample at home. At the last visit, participants will have these tests: Participants will relax and breathe normally while wearing a clear, plastic canopy that fits over their entire head. Blood samples will be taken before and after participants drink a sugary drink. Participants will be offered a large selection of foods for lunch. They will eat as much as they want. Then they will answer questions about how they feel about food and themselves.

Background: Cortisol is a hormone in the blood. Cortisol levels normally go down at night and up in the morning. Mild autonomous cortisol secretion (MACS) is a disease in which the body makes too much cortisol. MACS can cause high blood pressure, diabetes, and/or weight gain. Researchers think these problems may be caused by higher cortisol levels at night. Objective: To compare daily cortisol levels in people with MACS with those in healthy people. Also, to test a drug (ketoconazole) that may help lower cortisol levels in people with MACS. Eligibility: People aged 18 years and older with MACS. Healthy volunteers are also needed. Design: Participants with MACS will have a 2-night stay in the hospital. Day 1: A thin tube called a catheter will be inserted into a vein in the arm. Blood will be collected through the catheter every 2 hours starting at 8 PM. Participants will begin a 24-hour urine collection. Saliva will be collected every 6 hours for 24 hours. Day 2: Participants will take 2 tablets of the study drug ketoconazole with their evening meal. Blood will be collected via the catheter at regular intervals throughout the night. Day 3: Participants will leave the hospital in the morning. Healthy volunteers will be screened with a physical exam and blood tests. They will be tested to make sure they do not have MACS. To do this, they will take a drug (dexamethasone) at 11 PM on a day they choose; then they will return the next morning for a blood test. Healthy volunteers will have a 1-night stay in the hospital. They will have blood, urine, and saliva collected for 24 hours.

Background: Obesity and related illnesses cause at least 2.8 million deaths each year worldwide. Few treatments exist for obesity that are safe and widely available. A study drug (mirabegron \[MG\]) combined with a supplement (alpha-lipoic acid \[ALA\]) may help. Objective: To learn how MG and ALA can help the body process food. Eligibility: People aged 18 to 65 years with a body mass index between 30 and 45 kg/m2. Design: Participants will be screened. They will have a physical exam. They will have blood and urine tests and a test of their heart function. They will speak with a dietician. The study has two phases. Each phase begins with a 2-day stay in the clinic; then the participant will take the study drugs at home for about 4 weeks, followed by another 2-day stay in the clinic. They will also have outpatient visits about 2 weeks after each clinic stay. During the clinic stays, participants will undergo many tests: They will have a plastic tube (catheter) inserted into a vein in each arm. These will be used to draw blood and to infuse glucose (sugar) and insulin. They will have imaging scans. They will have a clear hard plastic shield placed over their head to measure oxygen and carbon dioxide as they breathe. Participants will take the study drugs at home. Both MG and ALA are taken by mouth with water. During one phase, participants will take MG plus a placebo. A placebo looks like the study drug but doesn t contain medicine....

Patients with hepatic steatosis due to alcohol will be offered liver biopsies when they enter a detoxification program. The first biopsy will occur in the first week of admission and the second in the fourth week when the steatosis has resolved. The hepatic transcriptome will be compared,

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.

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....

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.

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. ...

Background: Oncocytic (Hurthle cell) thyroid cancer (HTC) is a rare disease with few treatment options. Researchers are developing a radioactive drug that targets a protein that appears in high numbers on HTC cancer cells. Objective: To test a radioactive drug (177LuDOTA-EB-TATE) in people with HTC. Eligibility: People aged 18 years and older with HTC. The HTC must have failed to respond to conventional radioactive treatment; it must also have spread to other parts of the body. Design: Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans and a test of their heart function. 177LuDOTA-EB-TATE is infused into a vein. Participants will receive 4 infusions spaced 8 to 12 weeks apart. They will stay in the hospital for 4 to 10 days after each infusion. During and after each infusion, participants will remain in a lead-lined room until their radiation levels go down; this usually takes about 24 hours. Participants will have 4 to 6 follow-up visits in the weeks after each infusion. Procedures will vary at each visit, but may include more imaging scans; blood and urine tests; and tests of heart function. Participants will have 2 single-photon emission computerized tomography (SPECT) scans. SPECT scans show where the study drug is sticking to tumors or maybe other parts of their body. They will lie on a table while a machine rotates around them. Participants will fill in questionnaires about how their thyroid condition affects their life. Participants will have follow-ups visits for 5 years after their last study treatment.

Background: In a previous study, participants were lived at the NIH and randomly received either a low-fat or a low-carbohydrate diet for 2 weeks and then switched to the other diet for 2 more weeks. Participants who received the low-carbohydrate diet first lost more body fat at the end of the study than those who received the low-fat diet first. Researchers want to see if they can repeat that result in a longer weight loss study when participants live at home. Objective: To test the effects of diet order in people receiving either a low-fat or low-carbohydrate diet first for 4 weeks and then immediately switched to the other diet for another 4 weeks. Eligibility: Adults aged 19 to 50 years with a body mass index of 25 or more. Design: Participants will complete the study at their homes, but there will be 3 required visits to the NIH. Participants will drink a special type of water 2 weeks before the baseline NIH visit and collect urine samples at home to measure how many calories they burn. Before the diets begin, participants will visit the NIH for baseline testing when they will have a metabolism test while relaxing in a bed with a plastic hood over their head to collect the air they breathe out. They will have scans to measure their bone density and how much muscle and body fat they have. They will give stool, blood, and urine samples. Participants will be asked to eat a specific diet for 4 weeks followed by a different diet for 4 weeks. All meals will be delivered to the participants' homes. They will eat only the foods delivered. Participants will weigh themselves daily. They will wear a monitor to track their physical activity and a sensor to measure their glucose levels. They will prick their finger each morning to test a drop of blood for ketones. Participants will meet virtually as a group with the study team weekly. Participants will have two more NIH visits towards the end of each diet period....

Background: Many people in the United States are overweight or obese. Researchers want to learn why some people can overeat and not gain weight, whereas others who do not overeat still gain weight. Objective: To study factors related to food intake that can lead to weight gain over time. Eligibility: Healthy adults aged 18 to 60 years. Design: Participants will have 6 to 8 clinic visits over 2 years. The first 3 or 4 study visits will be 1 week apart. Procedures during visits may include the following: Collection of blood, hair, urine, and stool samples. Measurement of the waist, neck, thighs, and other parts of the body. Dual energy x-ray absorption (DXA) scan: Participants will lie still on a padded table while they are scanned to measure body fat. Physical activity monitor: Participants will wear a monitor on the wrist for 2 weeks. Cognitive tests: Participants will perform tasks to measure attention, memory, and brain function. Continuous glucose monitor. Participants will wear a device that measures their blood glucose for 1 week. Mixed meal test and stomach emptying test. Participants will drink a breakfast shake and swallow a dose of acetaminophen. Blood will be drawn over the next 4 hours. Resting metabolic rate: Participants will wear a clear hood over their head while they rest for 20 minutes. The hood will measure the gases they breathe. Breakfast and lunch test. Participants will eat a standard breakfast. They will be allowed to select from foods and eat as much as they like at lunch. They will be asked how hungry or full they are. Questionnaires. Participants will answer questions about their health, sleep, physical activity, and eating.

Background: Cortisol is a hormone in the blood. Cortisol levels normally go down at night and up in the morning. Mild autonomous cortisol secretion (MACS) is a disease in which the body makes too much cortisol. MACS can cause high blood pressure, diabetes, and/or weight gain. Researchers think these problems may be caused by higher cortisol levels at night. Objective: To compare daily cortisol levels in people with MACS with those in healthy people. Also, to test a drug (ketoconazole) that may help lower cortisol levels in people with MACS. Eligibility: People aged 18 years and older with MACS. Healthy volunteers are also needed. Design: Participants with MACS will have a 2-night stay in the hospital. Day 1: A thin tube called a catheter will be inserted into a vein in the arm. Blood will be collected through the catheter every 2 hours starting at 8 PM. Participants will begin a 24-hour urine collection. Saliva will be collected every 6 hours for 24 hours. Day 2: Participants will take 2 tablets of the study drug ketoconazole with their evening meal. Blood will be collected via the catheter at regular intervals throughout the night. Day 3: Participants will leave the hospital in the morning. Healthy volunteers will be screened with a physical exam and blood tests. They will be tested to make sure they do not have MACS. To do this, they will take a drug (dexamethasone) at 11 PM on a day they choose; then they will return the next morning for a blood test. Healthy volunteers will have a 1-night stay in the hospital. They will have blood, urine, and saliva collected for 24 hours.

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.

Background: Many people in the United States are overweight or obese. Researchers want to learn why some people can overeat and not gain weight, whereas others who do not overeat still gain weight. Objective: To study factors related to food intake that can lead to weight gain over time. Eligibility: Healthy adults aged 18 to 60 years. Design: Participants will have 6 to 8 clinic visits over 2 years. The first 3 or 4 study visits will be 1 week apart. Procedures during visits may include the following: Collection of blood, hair, urine, and stool samples. Measurement of the waist, neck, thighs, and other parts of the body. Dual energy x-ray absorption (DXA) scan: Participants will lie still on a padded table while they are scanned to measure body fat. Physical activity monitor: Participants will wear a monitor on the wrist for 2 weeks. Cognitive tests: Participants will perform tasks to measure attention, memory, and brain function. Continuous glucose monitor. Participants will wear a device that measures their blood glucose for 1 week. Mixed meal test and stomach emptying test. Participants will drink a breakfast shake and swallow a dose of acetaminophen. Blood will be drawn over the next 4 hours. Resting metabolic rate: Participants will wear a clear hood over their head while they rest for 20 minutes. The hood will measure the gases they breathe. Breakfast and lunch test. Participants will eat a standard breakfast. They will be allowed to select from foods and eat as much as they like at lunch. They will be asked how hungry or full they are. Questionnaires. Participants will answer questions about their health, sleep, physical activity, and eating.

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.

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....

Patients with hepatic steatosis due to alcohol will be offered liver biopsies when they enter a detoxification program. The first biopsy will occur in the first week of admission and the second in the fourth week when the steatosis has resolved. The hepatic transcriptome will be compared,

Background: Oncocytic (Hurthle cell) thyroid cancer (HTC) is a rare disease with few treatment options. Researchers are developing a radioactive drug that targets a protein that appears in high numbers on HTC cancer cells. Objective: To test a radioactive drug (177LuDOTA-EB-TATE) in people with HTC. Eligibility: People aged 18 years and older with HTC. The HTC must have failed to respond to conventional radioactive treatment; it must also have spread to other parts of the body. Design: Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans and a test of their heart function. 177LuDOTA-EB-TATE is infused into a vein. Participants will receive 4 infusions spaced 8 to 12 weeks apart. They will stay in the hospital for 4 to 10 days after each infusion. During and after each infusion, participants will remain in a lead-lined room until their radiation levels go down; this usually takes about 24 hours. Participants will have 4 to 6 follow-up visits in the weeks after each infusion. Procedures will vary at each visit, but may include more imaging scans; blood and urine tests; and tests of heart function. Participants will have 2 single-photon emission computerized tomography (SPECT) scans. SPECT scans show where the study drug is sticking to tumors or maybe other parts of their body. They will lie on a table while a machine rotates around them. Participants will fill in questionnaires about how their thyroid condition affects their life. Participants will have follow-ups visits for 5 years after their last study treatment.

Background: Type 2 diabetes is a disease that affects blood sugar levels. Complications can include heart and blood vessel (vascular) diseases. Rates of type 2 diabetes have tripled in children and young adults over the last 40 years. Vascular diseases are also increasing in young people. Objective: To learn more about factors, including type 2 diabetes, that may cause vascular disease in young people. Eligibility: People aged 12 to 25 years who (1) have type 2 diabetes; (2) are overweight but not diabetic; (3) or are lean and healthy. Biological parents are also needed. Design: Young participants will visit the NIH clinic once a year for up to 25 years. Each visit will take 4 days. Before each visit, participants will wear devices to track their sleep, activity, and blood sugar levels for 7 to 10 days. At each visit, participants will have tests including: Samples: They will provide blood, urine, and stool samples. Heart: They will ride a stationary bike for 6 minutes with stickers applied to their chest. Scans: They will lie on a bed that slides into a tube; the machine will take pictures of the inside of their body. Energy: They will wear a hood over their head to measure the air they breathe. Social stress: They will give a speech for 10 minutes to show their body s response to stress. Glucose: They will drink a sweet drink to see how their blood sugar changes. Biological parents will have 1 study visit. They will have blood tests. They will fill in questionnaires about their lifestyle and stress. ...

Background: Many people in the United States are overweight or obese. This natural history study will look into how life events during childhood can impact eating behaviors and weight gain as adults. Objective: To explore how childhood experiences affect adult eating behaviors. Eligibility: Healthy people aged 18 to 60 years. Design: Participants will have 3 clinic visits. They will be screened with blood tests. They will answer questions about their alcohol and tobacco use. At the next visit, participants will undergo these activities: Parts of their body (such as waist, neck, and thighs) will be measured with a tape. They will have an imaging scan to find out how much body fat they have. They will start wearing a device like a wristwatch that measures their physical activity. They will wear this device for up to 10 days. They will wear a device on their upper arm or belly that measures blood glucose (sugar) levels. Participants will wear this for 7-10 days. They will answer questions about their education, childhood, and routines. They will receive a kit to collect a stool sample at home. At the last visit, participants will have these tests: Participants will relax and breathe normally while wearing a clear, plastic canopy that fits over their entire head. Blood samples will be taken before and after participants drink a sugary drink. Participants will be offered a large selection of foods for lunch. They will eat as much as they want. Then they will answer questions about how they feel about food and themselves.

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. ...

Background: Obesity and related illnesses cause at least 2.8 million deaths each year worldwide. Few treatments exist for obesity that are safe and widely available. A study drug (mirabegron \[MG\]) combined with a supplement (alpha-lipoic acid \[ALA\]) may help. Objective: To learn how MG and ALA can help the body process food. Eligibility: People aged 18 to 65 years with a body mass index between 30 and 45 kg/m2. Design: Participants will be screened. They will have a physical exam. They will have blood and urine tests and a test of their heart function. They will speak with a dietician. The study has two phases. Each phase begins with a 2-day stay in the clinic; then the participant will take the study drugs at home for about 4 weeks, followed by another 2-day stay in the clinic. They will also have outpatient visits about 2 weeks after each clinic stay. During the clinic stays, participants will undergo many tests: They will have a plastic tube (catheter) inserted into a vein in each arm. These will be used to draw blood and to infuse glucose (sugar) and insulin. They will have imaging scans. They will have a clear hard plastic shield placed over their head to measure oxygen and carbon dioxide as they breathe. Participants will take the study drugs at home. Both MG and ALA are taken by mouth with water. During one phase, participants will take MG plus a placebo. A placebo looks like the study drug but doesn t contain medicine....

Study rationale High risk patients with differentiated thyroid cancer (DTC) require therapy with 131 I under thyroid stimulating hormone (TSH) stimulation. There are two methods of TSH stimulation endogenous by thyroid hormone withdrawal (THW) leading to hypothyroidism and exogenous by injection of human recombinant TSH (rhTSH Thyrogen). The appropriate 131-I activity utilized for treatment is either based on empiric fixed dosage choice or individually determined activity based on 131 I dosimetric calculations. Although dosimetry utilizing radioactive iodine isotope 131 I enables calculation of maximum safe dose, it does not estimate the tumoricidal activity necessary to destroy the metastatic lesions. The alternative radioactive isotope of iodine -124 I, used for positron emission tomography (PET) imaging, might be used for calculation not only the maximum safe131 I dose, but also to predict the absorbed dose in the metastatic lesions. Study objectives The primary objective of this study is to compare the 124 I -PET/CT lesional and whole body dosimetry in each individual patient with metastatic radioiodine (RAI)-avid thyroid cancer under preparation with rhTSH and THW. The secondary objective is to evaluate the predicted by PET/CT lesional uptake with the early response to therapy. Study design This is a phase 2 pilot prospective cohort study comparing the lesional and whole body dosimetry within each patient undergoing exogenous (rhTSH) and endogenous (THW) TSH stimulation and followed for 5 years. Interventions Each study participant will undergo rhTSH and THW-aided 124 I-PET/CT dosimetric evaluations and will be subsequently treated with THW-aided RAI activity based on dosimetric calculations enabling maximum safe dosage. The patients will be followed in 12+/-3 months intervals for 5 years. Sample size and population This pilot study will include 30 patients with high risk differentiated thyroid cancer presenting with distant and/or loco-regional metastases.

Background: Scientists have long used simple measures (such as height and weight) to estimate how much a person s body uses food (calories) as energy, as commonly called the metabolic rate. But metabolism varies among people with similar body sizes. Scientists now believe the old formulas for estimating metabolic rates may not work well for all people. Researchers want to find more accurate ways to measure a person s metabolism. Objective: This natural history study will examine the relationships between metabolism, body composition, and body surface area in a wide range of people. Eligibility: Healthy children and adults aged 2 years or older. Also, people aged 2 years or older with conditions that may alter metabolism. These may include diabetes, obesity, renal disease, or cancer. Design: Participants will spend 2 days and 1 night in the hospital. They will provide a medical history and answer questions about their activity levels, the foods they eat, and their lifestyle. They will also eat a special diet. Participants will undergo many tests: They will lie in a bed with a clear hood covering their head for 30 to 45 minutes to measure the gases in their breath. They will lie on a padded table for about 15 minutes while their body is scanned. They will stand on a platform while a 3D scanner measures their body. They will have a test to measure how fast an electric signal moves through their body. They will grip an instrument to measure the strength of their hands. They will drink salty water and provide blood and urine samples. Participants may be invited to return for these 2-day visits up to 8 times per year. Return visits must be at least 2 weeks apart.

Background: In non-alcoholic fatty liver disease (NAFLD), fat accumulates in the liver and can cause damage. Researchers want to learn what causes the damage NAFLD, and to see if a medication can help. Objective: To find out how the liver in people with NAFLD responds to feeding, and how this relates to their response to the drug semaglutide. Eligibility: People with NAFLD and healthy volunteers ages 18 and older Design: Participants will be screened with: Medical history Physical exam Blood tests Imaging: A machine will take pictures of the participant s body. Within 2-8 weeks of enrollment, participants will stay in the clinic for several days. This includes: Blood, urine, heart, and imaging tests For NAFLD participants only: A needle-like device will remove a small biopsy of the liver and fatty tissue. Participants will be alone in a special room for 5 hours. They will breathe through a tube under the nostrils. They will have blood drawn several times. The baseline visit concludes participation for healthy volunteers but NAFLD participants will contine. About 6 weeks after discharge, participants will stay in the clinic again and repeat the tests. They will get their first semaglutide dose by injection. Participants will have visits weeks 1, 2, 4, 8, 12, 16, 20, and 24 of treatment. Visits include blood tests. Participants will inject semaglutide once a week at home. At week 30, participants will stay in the clinic again and repeat the tests. Participants will have a final visit 12 weeks after stopping treatment. This includes blood and urine tests. ...