14 Clinical Trials for Various Conditions
Chronic kidney disease (CKD) is a burden of morbidity and mortality. Increased protein breakdown in skeletal muscle (wasting) and ectopic fat deposition are important determinants of poor clinical outcome in patient with CKD. Insulin resistance plays a critical role in skeletal muscle wasting and ectopic fat deposition. Glucagon-like peptide-1 receptor agonists (GLP-1RA) decrease ectopic fat deposition in patients with type 2 diabetes, prediabetes, obese and overweight subjects. The influence of GLP-1RA on ectopic fat deposition in CKD patients in unknown. The investigators' will test the hypothesis that GLP-1RA decreases intermuscular (ectopic) fat deposition in patients with stage 3-4 CKD. The investigators' will do so by addressing the following specific aims: Specific Aim 1: To test the hypothesis that GLP-1RA decreases intermuscular fat deposition in patients with stage 3-4 CKD. Specific Aim 2: To test the hypothesis that GLP-1RA improves skeletal muscle mitochondrial function in patients with stage 3-4 CKD. Specific Aim 3: To test the hypothesis that GLP-1RA improves physical performance in patients with stage 3-4 CKD. Specific Aim 4: To test the safety and feasibility of 12 weeks of dulaglutide 1.5 mg/wk administration as an adjunct therapy to the standard care of patients with stage 3-4 CKD.
This project, "A double-blind placebo-controlled randomized clinical trial assessing the efficacy of metformin for hepatic fat in adolescents and young adults with polycystic ovary syndrome", proposes exploring the use of novel and noninvasive methodologies in an at-risk adolescent and young adult population with polycystic ovary syndrome (PCOS) who may gain long-term health benefits from early detection and treatment of non-alcoholic fatty liver disease (NAFLD). PCOS is a common condition that frequently presents in adolescence and young adulthood and is defined by elevated androgens (male hormones) in the blood leading to 1. hirsutism and acne and 2. menstrual abnormalities or amenorrhea. Affected individuals are at increased risk of developing insulin resistance (a precursor of diabetes), NAFLD and lipid (cholesterol) abnormalities.These features are all associated with the metabolic syndrome, a rising major public health concern. Recently, an association between PCOS and NAFLD has been noted but has only been superficially studied in the adolescent and young adult population. The susceptibility of certain PCOS patients to developing NAFLD is theorized to be due to having underlying insulin resistance, elevated androgen levels, and a genetic predisposition. Metformin is an insulin sensitizing medication widely used to treat type 2 diabetes mellitus that may have beneficial effects on insulin resistance-related conditions including PCOS and NAFLD. Although widely used in PCOS, its effect on NAFLD in this group has not been previously studied. The primary aims of this proposal are: 1) To determine whether PCOS with liver fat \>/=4.8% treated with metformin for six months will have a decline in percentage liver fat compared to a placebo group. 2) To measure the association of the PNPLA3 I148M allele with NAFLD in PCOS at baseline (n=40). 2b) To measure the association of percentage liver fat with biomarkers of NAFLD, dyslipidemia, insulin resistance and body composition at baseline (n=40) and after a placebo-controlled intervention with metformin in PCOS with liver fat \>4.8% (n=20). The goal of this research proposal is to explore the use of novel and noninvasive technologies in a young and at risk population. Dr. Sopher hopes to use the results of this research to lay the groundwork for the prevention and treatment of NAFLD and other metabolic disorders in adolescents and young adults with PCOS and to prevent lifelong morbidity associated with PCOS.
The main objectives of this study are to collect pilot data to assess feasibility (accrual, retention, compliance), to estimate the variability of outcome measures, and to obtain preliminary estimates of treatment efficacy based on group differences in body composition (decreases in ectopic fat stores while maintaining lean mass), cardio-metabolic risk factors including glucoregulatory function (glucose, insulin), inflammation (C-reactive protein, IL-6), blood pressure and lipids (HDL, LDL, TC, TG), and measures of physical function and muscle strength. While this is just a pilot study, randomization will be used so that the investigators can obtain a realistic estimate of accrual (which is often less in a randomized trial) and an unbiased estimate of treatment efficacy. The investigators will accomplish these objectives by conducting a 2-arm, 3-month randomized, clinical trial in 24 older (60-79), abdominally obese (BMI ≥30 kg/m2 and waist circumference ≥ 102 cm and ≥ 88 cm in men and women, respectively) men and women. Participants will be randomized to a soy-based or animal-based, 3-month, hypocaloric dietary intervention to achieve our specific aims: Primary Aim: To determine our ability to recruit and retain older, obese adults to a 3 month soy-based meal replacement weight loss intervention and assess the study participant's ability to adhere to the intervention protocol (weight, compliance logs, serum isoflavones). Secondary Aims: 1. To estimate the variability of and obtain preliminary estimates of the effect of the soy-based meal replacement on measures of body composition, including abdominal (total, subcutaneous and visceral fat), liver, and pericardial fat; anthropometrics (body weight, waist/hip circumference); and whole body fat and lean mass. 2. To estimate the variability of and obtain preliminary estimates of the effect of the soy-based meal replacement on biomarkers of cardiometabolic risk including glucoregulatory function (glucose, insulin), inflammation (C-reactive protein, IL-6), blood pressure and lipids (HDL, LDL, TC, TG). 3. To estimate the variability of and obtain preliminary estimates of the effect of the soy-based meal replacement on physical function (short physical performance battery, 400-m walk) and muscle strength (grip and knee extensor strength) and size (CT thigh muscle). 4. To document any adverse events associated with the soy-based meal replacement.
This study evaluates how ectopic fat (in the pancreas, heart, liver and skeletal muscle), visceral fat, and subcutaneous fat changes following surgically induced weight loss using gastric banding. The investigators also evaluate whether changes in pancreatic fat content correlate with improvement in beta-cell function.
The relationship between obesity and insulin resistance is known, however the mechanism(s) associating obesity with insulin resistance is not well understood. Inflammation and accumulation of fat in non fat tissue (like muscle) are conditions found on obesity which could be the potential link between obesity and insulin resistance. This study is designed to test the effects of two different drugs on numerous features of the obesity and insulin resistance in subjects with impaired glucose tolerance. Impaired glucose tolerance is a condition where blood sugar is too high after drinking a sugary drink containing 75 grams of sugar. Impaired glucose tolerant subjects are insulin resistant and at risk of developing diabetes. The drugs to be used are fenofibrate and pioglitazone. Fenofibrate is used to reduce the amount of fat (triglycerides) in the blood while pioglitazone is routinely used to make the body more sensitive to insulin in patients with diabetes. The purpose of this study is to compare the effects of either of these two medications (pioglitazone and fenofibrate) alone or the combination of both on fat accumulation in body (muscle) and inflammation. The amount of fat accumulation in muscle is thought to affect insulin sensitivity. In addition, the changes in the level of proteins produced by fat tissues will be studied in response to the two medications in this study. These proteins are thought to be involved in diabetes and insulin resistance. These studies are designed to examine fundamental clinical mechanisms underlying the metabolic syndrome and diabetes.
The Visceral Adiposity Measurement and Observation Study
Adipose, or fat, tissue is a plastic organ that retains the ability to expand and store excess calories during positive energy balance in humans. The capacity of subcutaneous (subQ) adipose tissue to expand and remodel is an important determinant of obesity-related health complications, and impaired expansion of subQ fat tissue is thought to contribute to the risk of diseases such as the Metabolic Syndrome (MetS) and type 2 diabetes mellitus (T2D). The objectives of the study are to evaluate the changes and mechanisms of (subQ) adipose tissue expandability that occur as a result of short-term weight gain and to investigate the effects on cardio-metabolic health outcomes. Findings from this study will provide new insight into the dynamics of adipose expansion and remodeling during changes in energy balance and how this may impact future fat tissue function and metabolic health.
The purpose of this study is to investigate the effects of consumption of sugar sweetened and diet beverages on overall fat mass and the fat mass of various tissues implicated in the dysregulation of glucose metabolism. In addition, hypothalamic activity will also be investigated after acute exposure to sugar sweetened and diet beverages, and again after 6 months of daily consumption.
Obesity has become an epidemic worldwide. Data from our laboratory and others demonstrate that most of the excess morbidity from obesity is related to insulin resistance (IR). While total adiposity correlates with insulin resistance, not all obese individuals are IR. When obese IR individuals lose weight in response to caloric restriction, even moderate loss of body fat results in improved insulin sensitivity (IS). With massive weight loss, either dietary or surgical, even the most IR individuals can completely reverse their insulin resistance. But why is one individual IR at a BMI of 26 and another IS at a BMI of 35? There must be differences in the manner in which adipose cells/tissue respond to caloric excess and weight gain. One potentially unifying hypothesis with regard to obesity-associated insulin resistance is that those individuals who fail to respond to caloric excess/obesity with adequate adipocyte differentiation and expanded subcutaneous fat storage capacity develop increased circulating FFAs, ectopic fat deposition, stress on adipocytes, triggering localized and systemic inflammation and ultimately insulin resistance in skeletal muscle. Clearly, the best way to examine the human response to obesity is to challenge overweight individuals with the need to store excess triglyceride in adipose tissue. Specific aims are: 1. Test the hypothesis that impaired adipogenesis and fat storage capacity are associated with insulin resistance by comparing 1) cell size distribution; 2) gene markers of adipose cell differentiation; 3) differentiation of isolated preadipocytes in IR-prone vs IS individuals subjected to caloric excess. 2. Determine if circulating (daylong FFA, two-stage Insulin Suppression Test) and ectopic fat (MRI liver, CT abdomen) are worsened to a greater degree in IR-prone vs IS individuals subjected to caloric excess. 3. Determine whether differences in inflammation and/or innate or adaptive immune response are associated with insulin resistance by comparing differences in resident dendritic cells, macrophages and their activation profiles, changes in T-cell subpopulations, and other inflammatory mediators in IR-prone vs IS individuals who are subjected to caloric excess via overfeeding. 4. Exploratory: Evaluate IR-prone vs IS individuals for evidence of hypoxia and insufficient angiogenic response in response to caloric excess.
The purpose of this study is to investigate the acute and chronic effects of consumption fructose containing sugars and glucose in a real word setting when consumed in a manner and amount typical in the American diet.
The body shape of obese women varies between having the majority of fat either above the waist ("apple" shape) or below the waist ("pear" shape). The study will investigate what restricts: apple"-shaped women from being "pear"-shaped at the cellular level. Since "pear" shaped women tend to have better health, this study will open the door to future research in regulating body shape and thus improving health.
Participants in study C-1073-400 (NCT00569582) will be invited to participate in this extension study to examine the long term safety of mifepristone in the treatment of the signs and symptoms of endogenous Cushing's syndrome. Total treatment duration may be up to 12 months or longer at the discretion of the Investigator.
This is an observational study to confirm the presence of recurrent or persistent endogenous Cushing's syndrome in patients who have had primary surgical and/or radiation therapy for Cushing's disease and continue to manifest symptoms and signs of hypercortisolemia.
Patients will receive Corlux (mifepristone) daily for up to 24 weeks. Assessments of the signs and symptoms of Cushing's syndrome will be obtained.