Clinical Research Directory

Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity

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....

Graded Insulin Suppression Test P&F

The goal of this study is to learn about how the hormone insulin controls blood sugar in a variety of people. The main question it aims to answer is about how much insulin the body actually needs to maintain a normal blood sugar level. Participants will be asked to come in for a one-day study visit in which they will undergo a "graded insulin suppression test" ("GIST"). The GIST involves intravenous (into the vein) infusions of octreotide, a medication that turns off the body's own production of insulin, as well as replacement of insulin at two different levels (low and high), with or without replacement of glucagon, and glucose (sugar). The study investigators will check blood sugar levels every few minutes during the procedure to determine the effect of the two different insulin levels. This study will evaluate the GIST in both healthy volunteers and those at higher risk for type 2 diabetes.

Validation of the Snouda Metabolic Score for Phenotyping and Guiding Reversal in Type 2 Diabetes

This study tests a new tool called the Snouda Metabolic Score (SMS) that helps doctors identify the specific metabolic problems driving Type 2 Diabetes in each individual patient. Instead of treating all diabetic patients the same way, the SMS classifies patients into one of several metabolic phenotypes - patterns of dysfunction across five body systems: insulin resistance, chronic inflammation, hormonal disruption, gut microbiome imbalance, and mitochondrial dysfunction. Once classified, each participant follows a personalized 24-week lifestyle and nutritional protocol targeting their specific phenotype. The protocol includes dietary changes, structured exercise, targeted nutritional supplements, and optional intermittent fasting. Participants track their blood glucose daily and complete biomarker blood tests at the start and end of the study. The main goal is to determine whether the SMS tool accurately identifies metabolic phenotypes and whether phenotype-matched protocols produce better outcomes than standard approaches. The study measures changes in HbA1c, fasting insulin, C-peptide, inflammation markers, and whether participants achieve Type 2 Diabetes remission - defined as HbA1c below 6.5% without glucose-lowering medication. The study is conducted entirely online through the diabetesreversal.io platform. There are no clinic visits required. Participants must be adults aged 18 or older with a confirmed Type 2 Diabetes diagnosis and must not be pregnant or breastfeeding.

The Effects of Cognitive Behavioral Therapy on Insulin Resistance in People With HIV

The goal of this clinical trial is to learn if depression treatment improves insulin resistance, or how the body uses insulin to lower blood sugar, in people with HIV on HIV treatment. Researchers will compare an internet-based (online) depression treatment program called cognitive behavioral therapy with depression education. In the online group, participants will undergo 9 weekly treatment sessions. The education group will receive learning materials about depression and will be monitored every month. All participants will have 4 study visits over 12 months.

Metabolic Effects of Angiotensin-(1-7)

The overall purpose of this study is to learn more about the metabolic effects of angiotensin-(1-7) in the insulin resistant state associated with obesity. Pharmacologic approaches to increase angiotensin-(1-7) levels or its actions are currently in development for treatment of metabolic-related diseases such as obesity and type II diabetes, based on findings from animal studies. It is unclear if this peptide contributes to the regulation of metabolism in humans. The investigators will test if angiotensin-(1-7) infusion can improve insulin sensitivity measured by hyperinsulinemic-euglycemic clamp methods in individuals with obesity and insulin resistance. The investigators will also examine for changes in blood pressure and related hemodynamic and hormonal changes following angiotensin-(1-7) infusion.

Role of Aging and Individual Variation in Exercise Training Responsiveness

The primary purpose of this study is to assess the effects of aging on markers of physical reserve and exercise-induced adaptations in resilience in older adults who completed a structured exercise program within the last 15 years (Parent trial: STRRIDE-PD; NCT00962962). This feasibility pilot study will enroll up to 26 participants to complete a 6-month aerobic exercise intervention.

Identifying Risk for Diabetes and Heart Disease in Women

Background: \- Rates of diabetes and heart disease in women are increasing. Early recognition of risk could help women live longer and healthier lives. Race and ethnicity may affect the best kinds of tests to use to screen for these conditions. Researchers want to compare risk factors for diabetes and heart disease in African, African-American, and white women. Doing so may help identify the most effective screening test for each group. This study will look at healthy African, African-American, and white women who are federal employees and contractors. Objectives: \- To study risk factors for diabetes and heart disease in African, African-American, and white women. Eligibility: * Healthy African, African-American, and white women between 30 and 65 years of age who are federal employees or contractors. * For this study, African women must be born in Africa and have immigrated to the United States, and report that both parents are Africans. African-American women must self-identify as African-Americans, born in the United States, and have parents who both self-identify as African-American born in the United States. White women must self-identify as white and have parents who also self-identify as white. Design: * Participants will have four visits to study their risk factors for diabetes and heart disease. * The first visit is a screening visit. Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. They will also have an EKG test. Participants will also be shown how to fill out a 3-Day Food Record and wear an activity monitor called an accelerometer. The food record will keep track of how much participants eat for 3 consecutive days, including 1 non-working day. The accelerometer device will be worn for 3 days to monitor movement. * At the second visit, participants will have blood tests, an oral glucose tolerance test, and body fat measurements. They will also fill out questionnaires, review the food record, and have two imaging studies. * At the third visit, participants will have a longer glucose tolerance test. During the test, participants will receive both glucose and insulin and blood samples will be collected over several hours. Participants will receive lunch at the clinical center after the test. * At the fourth visit, participants will have a meal test. They will fast for 12 hours before the test. Participants will eat a specific meal and have blood samples taken during and after they eat. * Participants will discuss the results of these tests with the study doctors.

Precision Diets for Diabetes Prevention

With this study the investigators want to understand the physiological differences for people developing pre-diabetes and diabetes. The investigators hypothesize that different individuals go through different paths in the development of the disease. By understanding the personal mechanism for developing disease, the investigators will find a personalized approach to prevent that development. The investigators are also hoping to be able to find a biomarker that will pinpoint to the particular defect and thus, diagnose the problem at an earlier stage and have the information to give personalized diet recommendations to prevent the development of diabetes more effectively.

Cross-Sectional and Longitudinal Studies of "Pre-Diabetes" in the Pima Indians

Insulin resistance and a defect in early insulin secretion are risk factors for the development of type 2 diabetes mellitus. A recent longitudinal analysis which tracked the development of diabetes demonstrated that both insulin action and early insulin secretion deteriorate as individuals progress from normal to impaired glucose tolerance and then to diabetes. These results suggest that both inherent (apparent in normal glucose tolerant subjects who progress to diabetes and likely to have a genetic basis) and acquired (evident as individuals progress from NGT to IGT to diabetes and possibly environmental in origin) defects in insulin action and secretion contribute to the pathogenesis of type 2 diabetes. To identify the genetic and environmental determinants of diabetes we are continuing to determine: (1) if there are genes that segregate with metabolic risk factors for diabetes which might therefore be genetic markers for type 2 diabetes and (2) the mechanisms mediating genetic and environmental determinants of insulin resistance and impaired insulin secretion. \<TAB\> Volunteers for this study will be admitted to the clinical research ward where they will undergo several tests to determine body composition, oral and intravenous glucose tolerance and in vivo insulin action. In addition, in selected subjects, adipose and/or skeletal muscle tissue will be obtained by percutaneous biopsy for in vitro studies of gene expression and insulin action in these tissues. A transformed lymphocyte cell line will be established for each subject as a permanent source of DNA for genetic studies. Genetic markers for type 2 diabetes and insulin resistance will be sought by typing each individual at positional and functional candidate loci in the hopes of finding an association between these loci and obesity, insulin secretion, insulin resistance and/or type 2 diabetes.

Effect of Weight Loss on Intermuscular Adipose Tissue (IMAT) Signaling

The goal of this intervention study is to learn about how weight loss impacts molecular signaling of intermuscular adipose tissue (IMAT) in individuals with obesity. The main question it aims to answer is how inflammatory molecules secreted by IMAT promote muscle insulin resistance and inflammation, and how these same molecules are diminished after weight loss. Following screening visits involving body composition measures, blood testing, strength testing, and a thigh muscle biopsy, participants will go through a 12-week dietary intervention for weight loss. After 12 weeks, this will be followed by the same testing and biopsies that were completed before the intervention. Researchers will then compare outcomes of individuals who lost weight to individuals who did not lose weight.

Sleep Loss and Circadian Misalignment - Mechanisms of Insulin Resistance

The purpose of this study is to examine the impact of timed cortisol release or differently timed cortisol rhythms on insulin resistance in both men and women undergoing sleep restriction. Chronic sleep loss is highly prevalent, affecting 1 in 3 adults in the US. Chronic sleep loss causes stress which induces insulin resistance and leads to obesity and type 2 diabetes. Many factors contribute to sleep loss including shift work, environmental disturbances, sleep/circadian disorders and comorbid medical and mental health conditions. Sleep loss increases the stress hormone cortisol in the evening and decreases daytime testosterone. Examining these hormones in a controlled laboratory environment under different sleep schedules may help researchers find solutions for adults experiencing negative health consequences related to chronic sleep loss.

Adaptive Immune Response in Visceral and Subcutaneous Fat: Role in Human Insulin Resistance

The proposed study is designed to test the hypothesis that in human obesity, the balance of pro- and anti-inflammatory T cells in fat tissue is in fact related to macrophage phenotype and insulin resistance, and how it is related. This study is needed to confirm whether conclusions based on studies of visceral adipose tissue in mice are indeed applicable to humans. We also want to determine the relationship between insulin resistance/hyperinsulinemia and ability to lose weight in obese individuals.

Collection of Human Metabolic Tissues

This project aims at identifying new determinants of type 2 diabetes in severe obesity. To do so, a biological collection, including tissues of interest in the field of metabolism, will be collected during bariatric surgery in obese patients. Three different groups of metabolic status of patients, corresponding to different stages of evolution of the disease, will be constituted: type 2 diabetes, insulin resistance, insulin sensitivity. The main objective is to compare, between these 3 groups of patients, several biological processes that may be involved in the pathophysiology of type 2 diabetes and disorders associated with obesity, including: * Abnormalities of the transcriptome, proteome, metabolome in all target tissues (plasma, serum, muscle, subcutaneous and visceral adipose tissue, omental artery, liver) * Identification of metabolic signatures, protein and miRNA in plasma * Immunoinflammatory response in adipose tissue * Polymorphisms SNP from whole blood * Histological analysis of tissue sections This main objective will be studied on samples taken at the time of surgery Secondary objectives will be to study the changes in metabolites, proteins and miRNA in plasma level 3 and 12 months after the completion of surgery, according to the initial metabolic state.

Effects of Phytosterol Supplementation on Liver Function and Inflammatory Status in Patients With Nonalcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is considered one of the most common chronic liver diseases worldwide, it recently became a worldwide problem with high morbidity which requires further attention. The use of natural bioactive products such as phytosterols have shown anti-NAFLD effect with little to no side effects when used as a supplement in the therapeutic protocol of NAFLD, in many animals, and In vitro studies. Although the positive impacts of phytosterols on the prevention of hypercholesterolemia and improving liver functions have been reported in previous studies, further clinical experiments, especially human studies are needed to assure the effectiveness of phytosterols on improving liver enzymes, lipid profile, and insulin response in patients with NAFLD. In this study, we focus on the efficacy of phytosterol in a dose similar to the therapicutic lifestyle changes diet (TLC) recommendation with an aim to include it in the therapeutic protocol for NAFLD and to study the effect of some confounders that were excluded in previous studies on this relationship.

Machine Learning-Based Prediction of Insulin Resistance in Psoriasis Patients Emphasizing Interpretability

Psoriasis is a long-term inflammatory skin disease that can affect overall health. People with psoriasis have a higher risk of developing insulin resistance, a condition in which the body does not respond properly to insulin. Insulin resistance can increase the risk of diabetes, heart disease, and other serious health problems. Because insulin resistance often develops without clear symptoms, many patients are not diagnosed early. The purpose of this study is to identify which patients with psoriasis are more likely to develop insulin resistance and to create a tool that can help doctors estimate this risk for individual patients. The study will use existing medical records from two medical centers. Researchers will analyze information such as age, body weight, psoriasis severity, blood test results, other medical conditions, and medication history. Machine learning methods will be used to analyze these data and build a prediction model. The model will be designed to be easy to understand, so doctors can see which factors contribute most to insulin resistance risk. This study does not involve any new treatments or procedures. All patient information will be anonymized to protect privacy. The results may help doctors identify high-risk patients earlier and support timely monitoring and preventive care.

Impact of Preoperative Oral Branched-chain Amino Acids on Reducing Postoperative Insulin Resistance.

Postoperative insulin resistance refers to the phenomenon that the body's glucose uptake stimulated by insulin is reduced due to stress effects such as trauma or the inhibitory effect of insulin on liver glucose output is weakened after surgery. There is a clear link between postoperative insulin resistance and poor perioperative prognosis. Therefore, exploring interventions to reduce postoperative stress insulin resistance, stabilize postoperative blood glucose, and reduce postoperative complications are clinical problems that need to be solved urgently. In recent years, research on branched-chain amino acids and metabolic diseases has become a hot spot. Studies have found that in the rat model, preoperatively given a high branched-chain amino acid diet can inhibit postoperative insulin resistance and stabilize blood glucose levels. This research plan is to try to add branched-chain amino acids before surgery to observe the occurrence of postoperative insulin resistance in patients.

Sodium Bicarbonate and Mitochondrial Energetics in Persons With CKD

Skeletal muscle metabolic health is critical for mobility and an underrecognized target of metabolic acidosis in chronic kidney disease. Impaired muscle mitochondrial metabolism underlies poor physical endurance increasing the risk of mobility disability. The proposed project will use precise in vivo tools to study the pathophysiology of poor physical endurance in a clinical trial treating metabolic acidosis among persons living with chronic kidney disease.

The Effect of Ketogenic-caloric Restricted Diet on Metabolic Endotoxemia in Prediabetic Obese Adults

Insulin resistance increases the risk of type 2 diabetes and cardiovascular disease, with gut dysbiosis emerging as a contributing factor. Metabolic endotoxemia, characterized by elevated serum lipopolysaccharides (LPS), disrupts insulin signaling via inflammatory pathways. While dietary interventions may lower LPS levels and improve insulin resistance, evidence on the effectiveness of ketogenic diet in this context remains limited. This randomized controlled trial aims to assess the effects of a ketogenic-caloric restricted diet on metabolic endotoxemia, measured by serum LPS levels, in prediabetic obese Jordanian adults aged 18-40 years in Amman over 12 weeks. Ninety participants will be randomly assigned to one of three groups (n=30 each): a ketogenic-caloric restricted diet, a normal-fat caloric restricted diet, or a control group (normal-fat without caloric restriction). Anthropometric parameters and dietary intake will be evaluated at baseline, week 6, and week 12. Blood samples will be collected at baseline and week 12 for measuring fasting glucose, insulin, LPS, inflammatory cytokines. Dietary adherence will be monitored through food records. This study aims to provide new insights into the role of dietary interventions in modifying metabolic endotoxemia and improving insulin resistance.

Determinants of Insulin Sensitivity by Age, Sex, Race/Ethnicity, BMI, and PCOS Diagnosis

The study aims to investigate the relationship between fasting insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) across various demographic factors, including age, sex, race/ethnicity, BMI, and polycystic ovary syndrome (PCOS) diagnosis. By analyzing these variables, the study seeks to identify potential variations in insulin levels, which could provide valuable insights into the impact of different factors on metabolic health and the development of insulin-related conditions.

Effect of Daily Erythritol Versus Sucrose Intake Over 5 Weeks on Glucose Tolerance in Adolescents

Childhood and adolescence are crucial periods for prevention of obesity, as obese children are five times more likely to be obese at adulthood than lean children. To this purpose, sugar consumption should be reduced. The sugar alcohol erythritol is increasingly popular as sugar substitute in the food industry and is also recommended to diabetic patients. The substance is freely available. Recent acute studies show that erythritol has a positive influence on satiation and gastric emptying without affecting insulin and plasma glucose. In this trial, the investigators aim to assess the effect of a chronic intake of erythritol versus sucrose on insulin resistance in healthy adolescents. EryClot-Pilot: Erythritol is also produced by the human body and possibly elevated erythritol levels in the blood are an indication of an increased risk of cardiovascular disease, obesity or diabetes in the future. In a recently published study, a possible effect of erythritol on blood clotting function was described. In this in vitro experiment, increased blood clotting was observed when erythritol was added to clotting cells (platelets) in the test tube. Studies in humans on blood coagulation after administration of erythritol are missing so far. With a pilot study, the investigators study whether erythritol is detectable in the blood after administration of glucose and fructose. Furthermore, the erythritol level in the blood and a possible effect on the blood coagulation function after administration of erythritol will be investigated. These preliminary tests serve to clarify the data situation so that further studies can be based on them. The preliminary results of the EryClot\_Pilot study indicate that there appears to be no measurable effect of erythritol on thrombocyte aggregation. This implicates that there is a discrepancy between our results and the results reported in a recent published study. This is why we need to assess the effects of erythritol administration on more parameters of blood coagulation as well as in more subjects. Due to a study published in June 2024, there appears the need to investigate the effects of xylitol on blood clotting function as well. EryClot in vitro: In addition to the human EryClot study, we will conduct in vitro experiments (aggregometry assay after addition of erythritol or xylitol in human platelet rich plasma).

Carbohydrate Loading in Lowering Perioperative Insulin Resistance in Pediatric Surgery

It is a double blinded randomized controlled trial interventional study, examining the effect of carb loading given prior to surgery on preventing post operative insulin resistance in pediatric patients undergoing elective surgery

Effects of Intermittent Fasting on Insulin Resistance, Cardiac Metabolism, and Cerebral Perfusion

The overall purpose of the study is to investigate whether three weeks of intermittent fasting (alternate-day fasting, (ADF)) result in a more pronounced "metabolic shift" towards the use of ketone bodies than three weeks of Western diet. The investigators will use state-of-the-art PET/CT tracer techniques and well-established steady state kinetics methods for glucose and fatty acids. The study results will provide new insights into the physiological basis of the potential cardio-protective effects of ketone bodies during ADF and will determine whether ADF can help prevent and treat heart failure. Ketone bodies are produced in the liver as an alternative fuel when blood glucose levels are low, as can be seen with various types of diets or after strenuous exercise. The energy produced by breaking down ketone bodies has been shown to require less oxygen than breaking down glucose and fatty acids. In a previous study, the investigators observed that ketone bodies act as a kind of "super fuel" for the heart and improve the heart's energy utilization. It is still unknown how high ketone levels are needed to see these cardio-protective effects. As patients with insulin resistance and/or heart failure have a lower glucose uptake in cardiac tissue, and as energy production by the breakdown of fatty acids is oxygen-demanding, an elevated level of blood ketones can therefore potentially reduce the morbidity seen in patients with type 2 diabetes and ischemic heart disease. PET/CT is a non-invasive well-established imaging modality suitable for tracking the fate of metabolites, as most substances or metabolites can be labeled by a suitable PET isotope. PET has sufficient spatial and temporal resolution to enable direct quantification of e.g. uptake and oxidation rates and has been successfully used by the investigators' department to assess heart efficiency, oxygen consumption, and fatty acid metabolism. Currently, the investigators are in the process of validating the PET tracer 11C-beta-hydroxybutyrate (11C-3-OHB) as a radio tracer for human studies. The tracer will be able to detect changes in biodistribution and kinetics of ketone bodies during both Western diets and ADF. The subjects must go through two study periods of each 3 weeks in which the intervention is western diet (no restrictions) and intermittent fasting (fasting every other day), respectively. After both study periods, there will be an examination day with PET scans and various laboratory examinations.

Insomnia and Insulin Resistance

Insomnia symptoms are linked to metabolic syndrome (MetS), which includes abnormal glucose metabolism, insulin resistance (IR), and incidence of diabetes. Chronic sleep deficit is a major predictor of disease and early mortality. Further, insomnia is the most common sleep disorder in the United States. The recommended first line of treatment for insomnia is Cognitive Behavioral Therapy for Insomnia (CBT-I). CBT-I is a multidimensional treatment that targets the thoughts and behaviors that perpetuate insomnia symptoms over time. This study will explore CBT-I effects on MetS outcomes (ie. blood pressure, triglycerides, etc.) and provide preliminary evidence that CBT-I impacts IR and fasting glucose concentrations within this population. 20 subjects with insomnia will be recruited. They will be randomly assigned to either CBT-i or sleep hygiene. The intervention is 5 wks. Pre and post intervention, the investigator will have participants fill out a number of questionnaires, a daily sleep diary, 2 weeks of actigraphy measuring sleep and physical activity and there will be a single blood draw at the beginning and the end of the study.

Insulin Resistance as a Predictor of Pulsed Field Ablation Success in Atrial Fibrillation (HOMA-PULSE)

This study investigates whether insulin resistance, a metabolic condition where the body's cells respond poorly to insulin, can predict the success of atrial fibrillation (AF) ablation using pulsed field ablation (PFA) technology. Atrial fibrillation is the most common heart rhythm disorder, affecting 2-4% of adults. Catheter ablation is an effective treatment, but 20-40% of patients require a repeat procedure. Identifying patients at higher risk of ablation failure could improve treatment planning and outcomes. Scientific evidence suggests that insulin resistance - which can exist for years before diabetes develops - may contribute to electrical and structural changes in the heart that promote AF. However, no prospective study has systematically examined whether insulin resistance measured by the HOMA-IR index predicts ablation outcomes, particularly with the newest pulsed field ablation technology. HOMA-PULSE is a prospective observational study enrolling at least 120 non-diabetic patients undergoing their first AF ablation using pulsed field ablation at the Cardiocentrum, AGEL Hospital Trinec-Podlesi, Czech Republic. On the day of ablation, fasting blood samples are collected as part of routine preoperative care. A portion of these samples is used to measure insulin resistance (HOMA-IR index, calculated from fasting glucose and insulin levels) along with additional biomarkers including GDF-15, hs-CRP, NT-proBNP, IL-6, and IL-1beta. Detailed procedural and clinical data are recorded. Patients attend a single follow-up visit at 4-5 months post-ablation - a standard part of clinical care after AF ablation. The primary outcome is the clinical decision regarding need for repeat ablation (reablation), made by the treating physician blinded to the HOMA-IR result. The study does not involve any additional procedures, visits, or interventions beyond standard clinical care. The only research-specific element is the additional laboratory analysis of biomarkers from blood samples that would be drawn regardless of study participation. Additionally, intracardiac electrograms recorded during the ablation procedure will be analyzed using deep learning neural network models to extract electrophysiological features and evaluate whether insulin resistance has a detectable electrophysiological signature that can be captured by artificial intelligence. If a significant association between insulin resistance and ablation outcomes is confirmed, this could lead to new strategies combining ablation with metabolic optimization to improve success rates.