Metabolic Disease

This research study collects health-related information and blood samples to better understand how body composition, lifestyle habits, and diet influence meta-inflammatory monocytes (MiMos) in adolescents. The hypothesis of this study is that adolescents at risk for metabolic disease have enhanced MiMo related activities leading to insulin resistance.

Background: People s bodies need to break down food into the chemicals. These chemicals are used for energy and growth. Some people cannot process all chemicals very well. Too much of some chemicals can cause diseases. One of these diseases is called propionic acidemia (PA). People with PA can have problems with growth, learning heart, abdomen, and other organs. Researchers want to better understand how these problems happen. Objective: To learn more about propionic acidemia and the genes that might contribute to it. Eligibility: People at least 2 years old with PA who can travel to the clinic Some unaffected family members Design: Participants will have a 3 to 5-day hospital visit every year or every few years. Family members may have just 1 visit. During the family member visit, they may have: Medical history Physical exam Samples of blood and urine Questions about diet and a food diary Doctors and nurses may do additional studies: Samples of saliva, skin and stool Fluid from a gastronomy tube, if participants have one Dental and eye evaluations A kidney test - a small amount of dye will be injected and blood will be collected. Consultations with specialists A test of calories needed at rest. A clear plastic tent is placed over the participant to measure breathing. Stable isotope study. Participants will take a nonradioactive substance then blow into a bag. Photos taken of the face and body with underwear on Ultrasound of the abdomen Heart tests Hand x-ray Brain scan Participants may have other tests if study doctors recommend them. They will get the results of standard medical tests and genetic tests.

Background: People s bodies need to break down food into the chemicals. These chemicals are used for energy and growth. Some people cannot process all chemicals very well. Too much of some chemicals can cause diseases. One of these diseases is called propionic acidemia (PA). People with PA can have problems with growth, learning heart, abdomen, and other organs. Researchers want to better understand how these problems happen. Objective: To learn more about propionic acidemia and the genes that might contribute to it. Eligibility: People at least 2 years old with PA who can travel to the clinic Some unaffected family members Design: Participants will have a 3 to 5-day hospital visit every year or every few years. Family members may have just 1 visit. During the family member visit, they may have: Medical history Physical exam Samples of blood and urine Questions about diet and a food diary Doctors and nurses may do additional studies: Samples of saliva, skin and stool Fluid from a gastronomy tube, if participants have one Dental and eye evaluations A kidney test - a small amount of dye will be injected and blood will be collected. Consultations with specialists A test of calories needed at rest. A clear plastic tent is placed over the participant to measure breathing. Stable isotope study. Participants will take a nonradioactive substance then blow into a bag. Photos taken of the face and body with underwear on Ultrasound of the abdomen Heart tests Hand x-ray Brain scan Participants may have other tests if study doctors recommend them. They will get the results of standard medical tests and genetic tests.

Background: \- Researchers are interested in studying individuals who have known or suspected metabolic, inflammatory or genetic diseases that may put them at a high risk for heart diseases or diseases of their blood vessels. Depending on the condition being studied, both affected and nonaffected individuals may be asked to provide blood and other samples and may undergo tests to evaluate the heart, blood vessels and lung function. The testing is tailored to the individual and/or condition being studied. Nonaffected individuals may include relatives of affected individuals and healthy nonrelated volunteers. Objectives: \- To study individuals who have or are at risk for cardiovascular diseases, and in some cases their unaffected relatives and healthy volunteers. Eligibility: \- Individuals between 1 and 100 years of age. Participants may be healthy volunteers, individuals with cardiovascular diseases, or unaffected relatives of individuals with cardiovascular diseases. Design: * Participants will have some or all of the following tests, as directed by the study researchers: * Photography of the face and full body * Body measurements * Radiography, including chest or limb x-rays * Metabolic stress testing to study heart and muscle function * Echocardiography to study heart function * Magnetic resonance imaging (MRI) studies, including cardiovascular MRI, angiography, and contrast MRI, to study heart function and performance * Computed tomography (CT) angiogram to obtain images of the heart and lungs * Positron emission tomography (PET) imaging to study possible fat infiltration of the heart * Six-minute walk test to study heart, lung, and muscle function and performance * Vascular ultrasound to study blood vessel walls * Blood, tissue, and other specimens will be collected for research and testing, and will be taken either as part of the clinical study or during surgical procedures. * Follow-up studies may be performed under separate research protocols.

This research is being done to learn if a new type of haploidentical transplantation using TCR alpha beta and CD19 depleted stem cell graft from the donor is safe and effective to treat the patient's underlying condition. This study will use stem cells obtained via peripheral blood or bone marrow from parent or other half-matched family member donor. These will be processed through a special device called CliniMACS, which is considered investigational.

Background: Endocrine glands give off hormones. Researchers want to learn more about the disorders that affect these glands in children. These disorders might be caused by changes in genes. Genes contain DNA, which is the blueprint of how a cell works. Researchers want to identify the genes involved in endocrine and metabolic disorders. This might help develop new ways to diagnose and treat the disorders. Objective: To study the inheritance of endocrine or metabolism disorders. Eligibility: Children ages 3month-18 with known or suspected endocrine or metabolism disorders. Family members ages 3months-100. They may participate in the DNA part of the study. Design: Participants will be screened with a review of their medical records. Their parents or guardians will allow the records to be released. Participants will have a clinic visit. This may include a physical exam and medical history. Parents or guardians will give their consent for the study. Participants may have tests, surgery, or other procedures to help diagnose or treat their condition. These could include: Blood, urine, and saliva tests Growth hormone test Pituitary and adrenal function tests Picture of chromosomes Imaging tests. These may include X-ray, ultrasound, scans, or a skeletal survey. Genetic tests Sleep study Medical photographs If surgery is done, a tissue sample will be taken. Participants may have follow-up visits for diagnosis and treatment. Participating relatives will have one visit. This will include medical history and blood and saliva tests. The blood and saliva will be used for DNA testing.

The purpose of the Cardiovascular and Metabolic Sciences Biorepository is to collect and store information and biospecimens (blood, urine, stool, and heart tissue) from patients with and without cardiovascular and metabolic diseases to create a readily available biorepository of samples and related medical health information to expedite future research into the causes and consequences of cardiovascular and metabolic diseases.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally. While weight loss through lifestyle modification is the standard treatment, most patients regain weight limiting ultimate improvement in liver disease. On the other end of the spectrum, bariatric surgery has shown promise in the treatment of MASLD/metabolic dysfunction-associated steatohepatitis (MASH) due to its efficacy in inducing weight loss. Nevertheless, its adoption has been hindered by the perceived invasiveness of surgery. Over the past decade, endoscopic sleeve gastroplasty (ESG) has gained recognition as a promising minimally-invasive approach to weight loss. The procedure involves utilizing a Food and Drug Administration (FDA)-authorized endoscopic suturing device to reduce the gastric volume by 70%. Studies reveal that ESG is associated with approximately 18.2% weight loss at one year after the procedure, with sustained results for at least 10 years. Nevertheless, the effect of ESG on MASH remains unknown. In this study, the investigators will compare ESG + lifestyle modification versus lifestyle modification alone in treating histologic MASH. The study will randomize patients to one of two different treatment options: ESG + lifestyle modification or lifestyle modification alone.

The goal of this waitlist control clinical trial is to learn if the tailored LEARN 2 platform can prevent HIV-related comorbidities with shared risk factors in men ages 18 and older living with HIV. The main question\[s\] are: 1. Can the virtual environment improve quality of life among these participants? 2. Does the LEARN 2 platform effectively serve as prevention education for HIV comorbidity shared risk factors? Researchers will compare participants receiving the LEARN2 virtual environment intervention to those in a waitlist control group to see if the intervention leads to improvements in quality of life and reductions in risk factors. Participants will be asked to: 1. Engage with the virtual environment weekly. 2. Participate in virtual live health educator sessions. 3. Complete daily assessments of personal health behaviors through Ecological Momentary Assessment.

This is a Phase I, randomized, double-blind study designed to evaluate the safety, tolerability and pharmacokinetics of subcutaneous administration of SNS851 in healthy participants.

Background: Creatine transporter deficiency (CTD) is a genetic disorder that mainly affects the brain in males. CTD causes intellectual disability that can be mild to severe. People with CTD may have seizures and behavioral issues. They may have slow growth and tire easily. CTD may sometimes be confused with autism or other disorders. Better diagnostics are needed. The study team in an NIH study noted that the faces of children with CTD can look similar. For this natural history study, an expert will examine photos of children with CTD. Any shared traits found might help to diagnose CTD. Objective: To look for shared facial features of children with CTD. Eligibility: Males aged 2 to 40 years old with CTD who were in study 17-CH-0020. Design: Some participants in study 17-CH-0020 had pictures taken of their faces. The NIH study team wants to share these photos with a colleague in Canada. This person is an expert at evaluating how genetic disorders affect people s bodies. Participant data collected during the study may also be sent to this expert. This data may include diagnostic images and results from lab tests. Some children did not have their pictures taken during study 17-CH-0020. Parents are asked to take pictures of these children and send them to the study team. These photos can be sent to a secure portal. The photos can also be taken in-person during a clinic visit. The photos may be printed in clinical study journals. But this is not required. Parents will be asked to sign a separate consent before the photos are published....

Participants will be randomized into one of two different experimental groups: 1) Exercise group and 2) No exercise (control group). Subject participation in the study will involve a series of metabolic tests before and after participants undergo a 10% weight loss program (with or without exercise training depending on group randomization). After completing this weight loss portion of the study, participants will then be required to adhere to a high calorie diet program to regain half of the weight the participant lost - followed by the same series of metabolic tests.

This research study collects health-related information and blood samples to better understand how body composition, lifestyle habits, and diet influence meta-inflammatory monocytes (MiMos) in adolescents. The hypothesis of this study is that adolescents at risk for metabolic disease have enhanced MiMo related activities leading to insulin resistance.

The Continence, Sexual and Metabolic Health (CONTROL 4 LIFE) study will evaluate the recovery of continence, sexual function, and health outcomes in individuals who have undergone surgery for prostate cancer. The purpose of this study is to better understand the timelines of recovery for these outcomes after surgery for prostate cancer. As part of this study, all participants will receive resources offered by Alberta Health Services regarding pre- and post-prostatectomy care, including information on pelvic floor exercises. Through the CONTROL 4 LIFE study, the investigators will also be evaluating outcomes related to physical activity, fitness and quality of life. These assessments will enable the investigators to better understand how well and how long it takes for individuals to recover after surgery for prostate cancer.

Epidemiological studies are usually conducted in the general population in adults without complications or pathology at baseline. The results obtained are therefore often better designed for primary prevention use. The prediction of mortality risk in patients with complications and requiring hospital follow-up is less well known. The study purpose is to determine a mortality risk profile in a hospital cohort of patients with pathologies associated with metabolic diseases. Today the "multimaker" scores based on a panel of biomarkers - have significantly improved the discriminating power of prediction models existing in many pathologies. It is no longer a single biomarker that can improve risk prediction but a complete and cross-sectional profile that is sought after. We aim to establish a personalised mortality risk profile by combining clinical and biological parameters including metabolomics, genetics, transcriptomics and epigenomics by high throughput screening of biological samples.

This is a single-arm, open-label, multicenter, ascending dose Phase 1 trial that will enroll participants 18 to 75 years of age with dyslipidemias that are refractory to available treatments.

High body fat at midlife, as evidenced by overweight or obese body mass index (BMI), is increasingly understood as a risk factor for Alzheimer's disease. However, the underlying processes and mechanisms that may underlie this risk remains unknown. With this project, the Investigator proposes to create a new cohort of cognitively normal 120 midlife individuals, age 40-60 years. The investigator and research staff will characterize the participant's overweight or obese status using metabolic tests including, an oral glucose tolerance test, fasting plasma insulin, fasting plasma glucose, and hemoglobin A1c measurements. This testing will generate categories of metabolically abnormal overweight and obese (MAOO), metabolically normal overweight and obese (MNOO), and metabolically normal lean participants (MNLP). Research staff will evaluate differences between these groups on neuroimaging with the newer classification framework of Alzheimer's biomarkers with amyloid (A), tau (T), and neurodegeneration (N), or ATN. Neurodegeneration will be assessed by atrophy on brain MRI as reflected by regional volumes on Freesurfer. Staff will also evaluate MR neuroimaging markers for neuroinflammation using a newer method called diffusion basis spectrum imaging (DBSI), developed at the Mallinckrodt Institute of Radiology at Washington University in St. Louis in collaboration with The Charles F. and Joanne Knight Alzheimer's Disease Research Center (Knight ADRC).

The investigators are doing this study to learn more about how to prevent type 2 diabetes in teenage girls. The purpose of this study is to find out if taking part in a cognitive-behavioral therapy group, exercise training group, or a combination of cognitive-behavioral therapy and exercise training groups, decreases stress, improves mood, increases physical activity and physical fitness, and decreases insulin resistance among teenagers at risk for diabetes.

Background: Environmental exposures like pollution, diet, and stress can help cause human diseases, or make them worse. Researchers want to better understand how injury and inflammation are caused by these exposures. They want to collect biological and environmental samples and other data. They may use the samples to measure a range of factors, like hormones, toxins, and chemicals. This will help them improve their studies. Objective: To identify and understand how environmental exposures contribute to human disease. Eligibility: Healthy adults ages 18 and older Design: Participants will be screened with questions about their health history, demographics, and medicines they take. Participants may give blood, hair, stool, saliva, and/or urine samples. They may have a skin punch biopsy to collect skin cells. They may give fingernail or toenail clippings. They may give a sample of exhaled breath. Participants may give a sputum sample. They will inhale a saline mist and cough mucus into a cup. Participants may have their nasal passages brushed, scraped, or washed. Participants may give cheek cell samples. They will swish mouthwash and spit it into a cup. Participants who produce sperm may give samples. Participants may have bronchoscopy to collect fluid. A saline solution will be put into their lung and then suctioned out, washing areas of the lung. Participants may have a pelvic or transvaginal ultrasound. They may have lung function tests. Participants may collect household dust, urine, or stool at home. Participants will complete surveys about their health, diet, and exposures. Participation will last for one or more study visits. Participants may be contacted in the future to take part in other studies.

Study Purpose: The combination of caloric restriction and exercise is the most common first-line treatment for obesity-related disorders, yet we know very little about how these two very different treatments work together. A deeper understanding about mechanisms underlying the health benefits of adding exercise to a weight loss program will not only aid efforts to optimize more effective lifestyle interventions, but it can also uncover novel targets for the treatment/prevention of obesity-related diseases. Although a reduction in body fat is the fundamental adaptation to weight loss, we know almost nothing about the effects that adding exercise has on structural and functional changes within fat tissue that may further enhance metabolic health. This is very important because many obesity-related metabolic health complications are tightly linked with abnormalities in abdominal fat tissue. We argue exercise-induced modifications in abdominal fat tissue will reveal persistent health benefits even if some weight is regained Study Summary: 10% Weight Loss Phase - Subject participation in the study will involve a series of metabolic tests before, at midpoint, and after undergoing a 10% weight loss program (with or without exercise training depending on group randomization). During this, subjects will be randomized into one of two different experimental groups: 1. Moderate Intensity Continuous Training (MICT) exercise group 2. No exercise (control) group Follow-up Phase: After completing the metabolic testing post-weight loss, all study-related diet and exercise supervision will end and subjects will be free to make their own choices regarding diet and exercise/physical activity behavior. Subjects will then be asked to complete follow-up testing at 2-, 4- and 6- months post-weight loss. Total involvement in the study for each subject will likely be about 10-13 months (4-7 months during weight loss phase, 6 months during follow-up phase).

This pilot pre-post trial will address a gap in knowledge related to addressing modifiable risk factors for cardiometabolic disease through treating residual insomnia, sleep difficulties that remain after successful treatment of another condition, in the context of PTSD in understudied older adults. This study provides a non-medication treatment for PTSD called Cognitive Processing Therapy (CPT) followed by a non-medication sleep education and treatment program (Cognitive Behavioral Therapy for Insomnia, CBT-I) for sleep problems that remain after completing PTSD treatment in older adults with PTSD. The aims of this project are to evaluate 1) the added benefits of treating residual insomnia on sleep and PTSD symptoms; 2) the added benefits of treating residual insomnia following CPT on cardiometabolic risk biomarkers and quality of life; and 3) the durability of the sleep, PTSD, cardiometabolic and quality of life benefits of treating residual insomnia following CPT at 6-month follow-up in older adults with PTSD.

Managing patients with renal failure requires an understanding of the molecular mechanisms that lead to its occurrence (i.e. upstream of the disease), its worsening and its persistence (i.e. downstream), while also specifying the risk of worsening renal failure (risk stratification, intolerance to the treatment or complications (infectious, metabolic, cardiovascular, cancer…). Nephrogene 2.0 aims to study these different components of kidney, immune and solid organ transplantation (SOT)-related diseases.

This study is First In Human study for Encapsulated Porcine Islet Cells for Xenotransplantation (OPF-310). The purpose of this study to assess the safety, tolerability, and efficacy of OPF-310 transplantation and to define the recommended Phase 2 dose (RP2D) in adult subjects with unstable Type 1 Diabetes Mellitus (T1DM) and a level 3 (severe) hypoglycemic episode at least three times within the 1 year prior to enrollment despite treatment with a closed loop system (CLS) for at least 6 months.

Gastric myotomy has been performed for several years as a means of addressing chronic stenosis after sleeve gastrectomy and treating gastroparesis. The Pylorus Sparing Antral Myotomy (PSAM) technique has the opposite effect by leaving the pylorus intact and extending the myotomy proximally to the distal gastric body. PSAM was initially combined with ESG and shown to delay gastric emptying and provide greater weight loss without impacting tolerability (GCSI score) or the safety profile of the procedure (2 DDW GEM abstracts). PSAM has not been evaluated alone, without concomitant ESG. Since delayed gastric emptying alone is known to promote weight loss, it is thought that PSAM alone (without ESG) may provide similar efficacy, while reducing procedure time and adverse events. There have been no clinical studies that investigate the efficacy of PSAM independent of ESG. This pilot study aims to address this lack of information by evaluating the safety, tolerability, and short-term efficacy of PSAM, in addition to exploring its impact on gastric physiology. This will also provide data that may be used in designing a larger clinical trial.

This study aims to apply autologous differentiated myocyte subcutaneous transplantation in patients with muscle atrophy to explore its safety, feasibility, and efficacy.