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....

Effect of Insulin Lowering on Lipogenesis

The goal of this clinical trial is to compare a one-week course of diazoxide (2 mg/kg per dose x 14 doses) and placebo in people with obesity and insulin resistance (IR) with metabolic dysfunction-associated steatotic liver disease (MASLD). The main question it aims to answer are how mitigation of compensatory hyperinsulinemia with diazoxide affects hepatic de novo lipogenesis, a major contributor to MASLD pathophysiology. Participants will: * Take 14 doses of placebo over 7 days, followed 4-12 weeks later by either 14 doses of diazoxide (at 2 mg per kg of body weight per dose \[mpk\]) or another 14 doses of placebo, over 7 days * Take 18 doses of heavy (deuterated) water (50 mL each) over 7 days, twice * Have blood drawn and saliva collected after an overnight fast on four mornings over the course of the study * Undergo insulin suppression tests (IST) to assess the degree of insulin resistance at the end of each 1-week study period * Consume their total calculated daily caloric needs as divided into three meals per day Researchers will compare blood tests at the beginning and end of each 1-week study period in participants randomized (like the flip of a coin) to receive either placebo followed by diazoxide or placebo followed by placebo, to see how the drug treatment affects de novo lipogenesis, serum insulin, plasma glucose, and other serum lipid parameters (triglycerides, free fatty acids), among others.

Human Models of Selective Insulin Resistance: Alpelisib, Part I

The goal of this clinical trial is to understand how the blood sugar-lowering hormone insulin works in healthy adults versus those who are at risk for type 2 diabetes. The study will use a drug called alpelisib, which interferes with insulin's actions in the body, to answer the study's main question: does the liver continue to respond to insulin's stimulation of fat production even when it loses the ability to stop making glucose (sugar) in response to insulin. Researchers will compare the impact of single doses of both alpelisib and placebo (inert non-drug) in random order (like flipping a coin) in study participants. Participants will be asked to stay twice overnight in the hospital, take single doses of alpelisib and placebo (one or the other on each of the two hospital stays), and receive intravenous (into the vein) infusions of non-radioactive "tracer" molecules that allow researchers to measure the production of glucose (sugar) and fats by the liver. Measurements will be done both overnight, while participants are asleep and fasting (not eating or drinking other than water) and while consuming a standardized diet of nutritional beverages during the following day. The objective is to evaluate the effect of lowering insulin levels, while maintaining constant mild hyperglycemia, on plasma glucose and lipid levels.

Electro-Acupuncture for Obese Patients With Insulin Resistance

This clinical trial aims to evaluate the efficacy and safety of electro-acupuncture for obese patients with insulin resistance. 60 participants will be randomized and allocated to either the electro-acupuncture arm or the sham acupuncture arm.

Study of the Effect of Innate on the Inflammatory Response to Endotoxin

Background: \- Innate immunity is the process by which white blood cells and other parts of the immune system sense and respond to potential infections by causing an inflammation. Researchers are interested in studying how the body responds to certain environmental factors, and whether the body s response can contribute to chronic illnesses or diseases such as asthma and certain types of cancers. Objectives: \- To examine how specific genes and proteins in blood cells respond to environmental exposures. Eligibility: \- Healthy volunteers between 18 and 45 years of age. Design: * The study will involve one visit of 45 to 60 minutes. * Participants will be screened with a brief physical examination and finger stick to determine if they are eligible to donate blood for the study, and will complete a questionnaire about any medications or other drugs (e.g., cigarettes) they may be taking. * Participants will provide a blood sample for research purposes.

Determining Cell- and Spatially-distinct Skeletal Muscle Transcriptional Aberrations in Insulin Resistance

The purpose of this study is to find new signs or signals in muscle cells that can help us understand when the body isn't responding well to insulin (a condition called insulin resistance).

Impact of a Probiotic Supplementation With Lifestyle Modification on Liver Steatosis, Fibrosis, and Metabolic Health in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the new clinical term introduced in 2023 to redefine what was formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD). It is defined as fatty liver confirmed by imaging or biopsy, accompanied by at least one cardiometabolic risk factor (e.g., hyperglycemia, dyslipidemia, hypertension, or obesity). Its pathological progression ranges from simple steatosis to steatohepatitis, primarily driven by excessive energy intake, hepatic lipid accumulation, and insulin resistance. MASLD is currently the most prevalent chronic liver disease globally, with a prevalence rate of approximately 30-40%. However, there is no satisfactory pharmacological treatment, leaving lifestyle modification as the primary therapeutic approach. Many patients struggle to effectively adjust their habits, leading to persistent hepatic inflammation and damage, which may eventually progress to end-stage diseases such as cirrhosis and hepatocellular carcinoma. In many developed countries, MASLD has become the leading indication for liver transplantation, imposing a heavy burden on healthcare systems. Gut dysbiosis is closely linked to MASLD. An imbalance in the gut microbiota disrupts the gut-liver axis, leading to impaired intestinal mucosal barrier function. This allows bacterial components to enter the circulation, further triggering hepatic inflammation and abnormal lipid metabolism. Consequently, modulating the gut microbiota is considered a potential therapeutic strategy. Over the past decade, probiotics, prebiotics, and synbiotics have been extensively studied as non-pharmacological treatments for NAFLD. Multiple studies indicate that these products can reduce liver enzymes (AST, ALT), insulin resistance (HOMA-IR), and inflammatory markers (hs-CRP, TNF-α). The most effective combinations typically involve Lactobacillus, Bifidobacterium, and Streptococcus, with a recommended duration of approximately 12 weeks. However, the impact of these products on liver fibrosis, hepatic fat accumulation, and cardiometabolic risk factors remains inconclusive. The probiotic product to be tested consists of Lactobacillus salivarius AP-32, Lactobacillus rhamnosus bv-77, Bifidobacterium animalis CP-9, and Lactobacillus reuteri GL-104. This formulation complies with food safety regulations. In clinical studies, it had been proven as an effective adjuvant method that increased beneficial gut bacteria such as Akkermansia muciniphila and improved the control of blood glucose, lipids, and inflammatory markers. Study Objectives This study aims to investigate the efficacy of this probiotic product as an adjuvant therapy alongside lifestyle modifications in adult patients with MASLD. We will evaluate its impact on: 1. The degree of liver fibrosis and steatosis 2. Cardiometabolic risk factors (BMI, waist circumference, blood lipids, and blood glucose). 3. Inflammatory markers. 4. Gut microbiota composition.

MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity

This Phase 2a study evaluates whether 12 weeks of treatment with investigational MOTS-c improves insulin sensitivity compared with placebo in adults with prediabetes and overweight/obesity. Participants are randomized 1:1 to MOTS-c or placebo, receive standardized lifestyle counseling, and are followed for safety through Week 16.

Effects of Antipsychotics on Brain Insulin Action in Females

Females treated with antipsychotics have higher rates of comorbid metabolic syndrome than males. Despite this, females have historically been excluded from many mechanistic studies due to confounding effects of menstrual cycles. Recent evidence suggests that brain insulin resistance may be an underlying mechanism through which antipsychotics may exert their metabolic side effects. This study seeks to investigate how brain insulin action differs in females according to their menstrual cycle phase, and how a high metabolic liability agent such as olanzapine might interrupt these differential insulin effects. Young healthy females will be given olanzapine and intranasal insulin to test how these treatment combinations change brain processes. Participants will be tested during both the first half of their menstrual cycle (follicular phase) and the second half of their cycle (luteal phase). The investigators predict that intranasal insulin will change MRI-based measures in females, in a comparable way to males, in the follicular phase only. Adding olanzapine will block these effects of insulin in females in the follicular phase. This investigation has the potential to generate new knowledge in an area of significant unmet need. Demonstrating that antipsychotics disrupt brain insulin action, evidenced by inhibition of recognized effects of insulin on neuroimaging measures, will provide novel insights into currently poorly understood mechanisms.

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.

Effect of a Multidomain Intervention Plus Turmeric on the Prevention of Cognitive Decline in People Over 55 Years of Age With Insulin Resistance.

Introduction: The Insulin resistance itself has been recognized as an independent risk factor for dementia development. Insulin plays an important role in the regulation of muscle function and the processes of learning and memory. Insulin resistance is associated with increased inflammation and oxidative stress. These processes are involved in the pathophysiology of neurodegenerative diseases. Thus, reducing IR could have implications for improving metabolism, muscle, and cognitive function. Methods and analysis. The investigators will conduct a randomized, double-blind, placebo-controlled clinical trial in which a multidomain program, including an aerobic and cognitive exercise program, will be evaluated. The latter is an exercise program conducted on a checkered mat and will be randomized to participants receiving turmeric plus black pepper or placebo. Participants are affiliated with the Mexican Social Security Institute (IMSS) and are between 55 and 74 years old. The program will last for 24 weeks; after 52 weeks, it will be repeated. The outcomes that the investigators will evaluate are: global cognitive function, specific cognitive function, and the investigators will evaluate serum markers of inflammation, oxidative stress, and GSK-3beta levels. The effect of the interventions on each variable will be analyzed by ANOVA, and a multivariate analysis study with multiple linear regression will be conducted. Ethics and dissemination of the study: the study was approved by the IMSS National Ethics and Research Committee all participants provided written informed consent prior to their participation.

ActiveGirls: Physical Activity, Hormone Health, and Diabetes Risk in Early Adolescence

This study explores how a physical activity program can affect hormone health and diabetes risk in girls ages 8-12 who may be at higher risk. The study aims to address: * Does the 'ActiveGirls' program meet the needs of girls and families in engaging them to increase physical activity? * What is the trend of markers of diabetes risk and puberty hormones over a 1-year period and how are these levels related to physical activity levels? Participants in this study will either: * Participate in a 'full' intensity intervention that includes educational messages (text/email) as well as health coaching visits to support physical activity over a 6 month period * Participate in a delayed 'lower intensity' intervention that includes only educational messages (text/email) * Participants in both groups will complete at-home activity monitoring, two study visits for check-ups and tests, and surveys

Glucose Profiles in Women With Polycystic Ovary Syndrome

Polycystic ovary syndrome is a very common condition that is associated with metabolic complications. Patients with polycystic ovary syndrome exhibit insulin resistance and are at greater risk to develop type 2 diabetes. This syndrome is heterogeneous, classified according to 4 phenotypes (A-D). It seems that certain phenotypes are less exposed to insulin resistance and metabolic complications. However, only a few studies have evaluated the glucose profile according to phenotype. New technologies now make it possible to monitor glucose levels continuously. The aim of this project is to evaluate glucose profile parameters using continuous glucose monitoring, and to compare these profiles according to different PCOS phenotypes.

Evaluating the Influence of Diet-induced Weight Loss on Fat (Adipose) Tissue's Insulin Sensitivity and Testosterone Synthesis in Women With Overweight or Obesity, Insulin Resistance, and Hyperandrogenemia

The investigators will measure plasma concentrations of the hormones insulin and testosterone as well as measures of insulin sensitivity in women with overweight or obesity who have insulin resistance (IR). Women who meet these criteria that also have elevated total or free testosterone will be eligible to participate in the diet intervention. The dietary intervention is designed to produce a 5% reduction in starting body weight to test whether weight loss will acutely lower fasting insulin and testosterone concentrations.

Empagliflozin Adjunctive Therapy in Bipolar Depression

Bipolar disorder is a long-term mental health condition that causes mood changes, with depressive episodes being the most frequent and disabling. Many people do not fully recover with current treatments, showing the need for new therapeutic options. Recent research shows that insulin resistance (IR), a condition in which the body does not respond well to insulin, is common in people with bipolar disorder. It is linked to more severe mood symptoms, poorer treatment response, and higher risk of heart disease. IR may raise inflammation and affect how the brain uses energy, which can influence mood regulation. Empagliflozin is a medicine approved for type 2 diabetes. In addition to its metabolic and heart benefits, studies suggest that it may also protect the brain and reduce inflammation, possibly helping to improve mood. This open-label, proof-of-concept clinical trial will test how well empagliflozin works and how safe it is as an add-on treatment for people with bipolar depression and insulin resistance. A total of 20 adults with bipolar disorder type I or II, currently in a depressive episode, will take part in the study over a 12-week period. The main goal is to see whether empagliflozin can lower depressive symptoms, measured with the Montgomery-Åsberg Depression Rating Scale (MADRS). Other measures include changes in insulin resistance and incidence of adverse events. The study aims to explore whether improving insulin resistance can help both mood and metabolic health in people with bipolar disorder, guiding future clinical research.

Glucose Evaluation Through Continuous Glucose Monitors in Polycystic Ovary Syndrome

PCOS is the most common endocrine disorder of reproductive aged women. In addition to menstrual and endocrine abnormalities, PCOS is characterized by insulin resistance and glycemic dysregulation. The pattern of glycemic abnormalities among patients with PCOS may be different than the general population, as evidenced by invasive, time consuming, and costly procedures such as the euglycemic clamp or oral glucose tolerance test. Continuous glucose monitoring (CGM) offers an opportunity to evaluate glycemic status in real world conditions. Furthermore, use of a CGM has been found to improve glycemic status among those with prediabetes and diabetes, but little is known about utility among patients with PCOS. The investigators thus seek to 1) characterize glycemic status using CGM among patients with PCOS and 2) assess the impact of CGM use on metabolic and reproductive health in patients with PCOS.

MRI Assessment of Pancreatic Fat Changes and Islet Function Recovery After Bariatric Surgery in Obese Patients

This study evaluates changes in pancreatic fat and recovery of pancreatic function in obese patients undergoing laparoscopic sleeve gastrectomy (LSG), a weight-loss surgery. Obesity can cause fat to accumulate in the pancreas, which may impair insulin production and lead to type 2 diabetes. This study uses magnetic resonance imaging (MRI) to measure pancreatic fat before and after surgery to understand how weight loss affects pancreatic function. About 50 obese patients (BMI \> 32 kg/m²) aged 16-60 years who are scheduled for LSG will be enrolled. Participants will undergo MRI scans of the pancreas and blood tests before surgery and at 1, 3, and 6 months after surgery. The MRI uses a safe, non-invasive technique called Dixon imaging to measure fat content in different parts of the pancreas (head, body, and tail). Blood tests will measure fasting glucose, insulin, C-peptide, and HbA1c to assess pancreatic function. The study aims to determine whether reduction in pancreatic fat after weight-loss surgery is associated with improved insulin secretion and reduced insulin resistance. This information may help doctors better understand how bariatric surgery improves metabolic health and guide postoperative patient management. Participation involves no additional risk beyond routine clinical care. All MRI scans and blood tests are part of standard postoperative monitoring for bariatric surgery patients.

Effects of Chestnuts on Postprandial Glycaemic Response

Nut consumption is known to improve health outcomes, such as reducing the risk of chronic diseases like diabetes, cognitive impairment, and cardiovascular diseases. While most research has focused on walnuts and almonds, there is limited information on the health benefits of chestnuts. Chestnuts are unique among tree nuts due to their high starch and fibre content, along with vitamins E and C, minerals (potassium, phosphorus, magnesium), and polyphenols. Evidence from in vitro and animal studies suggests that chestnuts may positively affect health by regulating the gut microbiome, lowering the glycaemic index, and providing antioxidant benefits. The food industry is also exploring new uses for chestnuts, particularly in gluten-free products, due to their nutritional benefits and good taste. Nonetheless, no research has investigated the health effects of chestnuts in humans. By addressing this gap in the literature, the study may lead to the development of new dietary strategies for improved health outcomes.

Effects of Cranberry on Gut and Metabolic Health

The consumption of plant-based foods, particularly berries, has been associated with improved health due to their high content of bioactive compounds. Among these, polyphenols-especially proanthocyanidins (PACs)-may offer protective effects against chronic diseases related to overweight and obesity. Cranberries are naturally rich in PACs and may positively influence metabolic health by modulating the gut microbiota. However, their specific effects on intestinal integrity and broader metabolic outcomes remain underexplored. The primary aim of this study is to assess the effects of cranberry supplementation on glucose metabolism, insulin sensitivity, blood lipid levels, and the composition and function of the gut microbiota in overweight and obese individuals. This randomized, double-blind, placebo-controlled, crossover clinical trial will include two 12-week intervention periods-one with a cranberry beverage and one with a placebo-separated by a 4-week washout period and preceded by a 2-week lifestyle stabilization phase. Participants will undergo comprehensive metabolic assessments (glucose control, insulin sensitivity, lipid profile), body composition analysis, gut microbiota profiling, and liver fat imaging (MRI in a subsample of female participants). Additional evaluations will include markers of inflammation, appetite regulation, intestinal health, and lifestyle factors.

Role of Sympathetic Vasoconstriction on Insulin-Mediated Microvascular Recruitment and Glucose Uptake in Obesity

The purpose of this study is to better understand the contribution of sympathetic vasoconstriction to impaired insulin-mediated vasodilation and subsequently insulin-mediated glucose uptake. The investigators will test the hypothesis that removal of sympathetic vasoconstriction can result in improvement in insulin-mediated vasodilation and subsequently sensitivity to insulin-mediated glucose uptake.

Mitochondrial Substrate Utilization in the Diabetic Human Heart

Diabetes can lead to heart failure independently, but the underlying causes remain incompletely understood. The main aim of this study is to identify differential regulation of mitochondrial substrate utilization and complex activity in heart failure and type 2 diabetes mellitus (T2DM). For this, we will conduct a prospective, observational study to examine myocardial mitochondrial oxidative function and related metabolic parameters, gene expression, histological markers, and inflammation in cardiac tissue from patients with heart failure or patients after heart transplantation. We will further assess cardiac function using cardiac magnetic resonance imaging with and without stress protocols and magnetic resonance spectroscopy. Glycemic control/T2DM will be characterized by oral glucose tolerance tests. The results of this project will help to better understand the cellular mechanisms of the development of diabetic cardiomyopathy and contribute to the development of early diagnostic, as well as therapeutic approaches for the prevention and treatment of diabetic cardiomyopathy.

Impact of Starch Digestibility on Glycemic Variability and Control, Cardiometabolic and Inflammatory Profiles, Microbiota and Intestinal Health in Subjects With Insulin Resistance

To study the potential impact of a diet rich in both Slowly Digestible Starch (SDS) and Resistant Starch (RS), we propose a 2-month nutritional intervention study in which we will study the evolution of carbohydrate variability and metabolism and health-related parameters in 40 volunteers with insulin resistance. Regular sampling of blood, urine and faeces as well as continuous measurement of blood glucose levels will be performed to assess changes in blood glucose levels, insulin resistance, lipid metabolism, inflammation and the composition of the microbiota following the introduction of starch products rich in SDS and RS into the diet.

Exercise, Insulin Resistance, and Chronic Pain in Postmenopausal Women.

This study aims to investigate the effects of a combined exercise program on chronic pain in postmenopausal women, considering insulin resistance as a potential physiological mediator. The intervention will assess changes in pain intensity, metabolic and inflammatory biomarkers, psychosocial factors, and body composition. The findings may contribute to understanding the metabolic mechanisms underlying chronic pain in postmenopausal women and support exercise as a non-pharmacological therapeutic strategy.

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.