View clinical trials related to Metabolism.
Filter by:This will be an open-label, non-randomized, absorption, metabolism, and excretion study of Lurasidone administered in a suspension at 40 mg to 6 normal healthy male subjects in a postprandial state
Early childhood (~3-7 years of age) is an important window for determining body composition trajectory and may be a critical period for the development of tissue partitioning patterns that influence obesity risk. As adiposity accelerates during this critical period, deposition/ preservation of fat stores may be sustained at the 'expense' of other tissues; i.e. energy homeostasis may be inherently biased toward fat gain. The type and amount of tissue mass accrued in early childhood has implications for metabolic profile, glucose/insulin homeostasis, hormone profile and resting energy expenditure. The interplay between fat and bone deposition represents a physiologic trait enabling the body to choose between shuttling 'energy' towards accrual of a particular tissue. Plausibly the phenotype underlying obesity and diabetes risk may be determined by the differentiation of cell type (adipocyte, osteocyte, etc.) during this early stage of growth and development. In vitro studies demonstrate transdifferentiation under the influence of specific external stimuli, which can switch phenotypes toward other cell lineages. Further, rodent models have demonstrated that exposure to stimuli (exercise) early in life may prevent excess fat mass accrual in adulthood, even when the stimulus is later removed (animals are no longer exercising). Children's early experiences (engagement in physical activity vs. sedentary behavior) may 'environmentally induce' alterations in body composition and predispose individuals to obesity throughout life. Aim 1. To examine the associations between body composition via DXA and objectively-measured physical activity/inactivity. 1. Hypothesis 1.1: There is a positive association between physical activity and bone mass. 2. Hypothesis 1.2: There is a positive association between sedentary behavior and total fat mass. Aim2. To examine the associations between adipose tissue distribution via MRI and objectively-measured physical activity/inactivity. 3. Hypothesis 2.1: There is an inverse association between physical activity and bone marrow adipose tissue. 4. Hypothesis 2.2: There is a positive association between sedentary behavior and bone marrow adipose tissue.
A key factor in the determination of body composition over the lifecourse is fat accumulation during childhood. Periods of life associated with the greatest changes in organ development and growth, i.e. early childhood, have the most significant effect on body composition, energy balance, and metabolism. Early childhood (age 3 to 7 years) represents a critical transition for the basis of adaptability in body composition, due to the rapid growth and development that occurs. Plausibly the phenotype underlying obesity and related health risk may be determined by body composition during this critical period. Our previous research in children has consistently indicated that HA children accumulate greater amounts of fat, particularly in the intra-abdominal compartment, even at similar a BMI, and lower bone mineral content relative to EA children. The reason for these differences in body composition over the lifecourse is not clear. Racial/ethnic differences in risk factors for health, including 'thriftiness' in body fat accumulation are often evident before the age of 7, suggesting that the racial/ethnic differences in energy utilization and subsequent fat storage may be accounted for by genetic make-up, the environment (e.g. diet), or an interaction of the two. The physiologic or behavioral process(es) that cause(s) certain children to take a trajectory towards obesity while others accrue less fat is not known. However, the economic decision of fuel utilization is a physiologic trait enabling the body to choose between shuttling 'energy' towards accrual of a particular tissue (e.g. bone vs. fat) and this trait likely has a genetic component. This genetic component may be embedded in fat storage capacity evolved from gene by environment interactions that promote thrift, particularly conserved in some populations. Although genetic background plays a role, it not known whether there is a relationship between genetic background, known candidate genes or candidate pathways and environmental contributors (e.g. diet) that impact body composition trajectory. Of central importance to our understanding of early fat mass accumulation in health disparities are the mechanisms that lead to chronic disease progression. It is likely that variations within candidate genes may have a differential impact on individuals based on their genetic background. It is also probable that body composition is influenced by many genes, often within the same metabolic pathways, with small individual effects. These genes may not be significantly associated individually, but when examined as a unit (in a candidate pathway or gene-gene interaction framework) the association becomes significant. Further, children's early environmental exposures (e.g. diet) may interact with both genetic background and variations in candidate genes along resulting in alterations in body composition that predispose HA to excess fat accumulation throughout the lifecourse. To that end, the following specific aims will be evaluated: Aim 1. To examine the associations between genetic admixture and body composition in children aged 3-7 years after controlling for dietary intake. 1. Hypothesis 1.1: There is a direct association between Amerindian admixture and fat mass and in inverse association between Amerindian admixture and bone mass. 2. Hypothesis 1.2: There is a direct association between energy intake and fat accumulation and the relationship will be particularly evident in individuals with a greater proportion of Amerindian admixture. Aim 2. To examine the associations between genetic admixture and bone marrow fat in children aged 3-7 years after controlling for dietary intake. 1. Hypothesis 2.1: There is a direct association between Amerindian admixture and bone marrow fat. 2. Hypothesis 2.2: There is a direct association between energy intake and fat accumulation in bone marrow and the relationship will be particularly evident in individuals with a greater proportion of Amerindian admixture. Aim 3. To examine the relationship between variation in candidate genes and pathways and Amerindian admixture controlling for dietary intake. a. Hypothesis 3.1: Amerindian admixture will be associated with variations in candidate genes and pathways known to be associated with fat accumulation.
This study was to determine the ADME and metabolites of Proellex following a single oral dose of 25 mg.
The aim of the investigators research is to see if variants in a particular gene (named CYP2B6) affect how the body metabolizes (breaks down) certain medications, including the drug bupropion. Bupropion is widely used in the treatment of depression and for helping people quit smoking. Genes are portions of DNA that code for particular proteins in the body. The investigators are studying the gene that codes for a protein called CYP2B6. Differences in the structure of the gene are called variants and may mean that a person metabolizes a drug faster or slower than a person with a different variant.
The aim of this study is to evaluate the effects of a supplementation of citrulline for three weeks in elderly malnourished and hospitalised subjects on muscle protein synthesis.
The purpose of the study is to evaluate if AZD3480 inhibits Cytochrome P450 1A2, 2C19, 3A4, 2C8, 2B6 and UGT1A1 activity.
Military personnel are exposed to the insecticide permethrin when using the DOD Insect Repellent System. A urinary metabolite of permethrin that is in high abundance and is relatively stable may be an ideal biomarker of exposure to this pesticide. Monitoring such a biomarker can prevent over-exposure. The objectives are to identify the most abundant human urinary metabolite following dermal exposure; to utilize this information to develop rapid laboratory-based and field portable methods to monitor the degree of an individual's exposure to permethrin.
The purpose of this study is to examine the effects of growth hormone during fasting in healthy lean men.
This study will evaluate the effects of genetics on metabolism of the anti-HIV medicine efavirenz (Sustiva) and will see if Efavirenz interacts with bupropion (Zyban or Wellbutrin), a drug commonly used to treat depression and to help people quit smoking. Efavirenz is metabolized by an enzyme called CYP2B6, which is thought to be more active in some people than in others, depending on their genetic makeup. The rate of metabolism of the drug can affect how the body responds it and perhaps the ability of the HIV virus to develop resistance to it. Healthy volunteers between 18 and 55 years of age who are non-smokers and HIV-infected men and women 18 years of age and older who are taking efavirenz along with two or three nucleoside reverse transcriptase inhibitors may be eligible for this study. Candidates are screened with a medical history and physical examination and blood tests, including tests to determine which genes they have for four different proteins or enzymes (CYP2B6, CYP3A4, CYP3A5, and MDR1) that metabolize drugs. Participants are assigned to one of three groups for the following procedures: -HIV-infected individuals: Blood samples are drawn to measure efavirenz levels, as follows: On the last day of taking efavirenz, the subject skips his or her usual evening efavirenz dose the night before sampling. The next morning at clinic, a catheter (flexible plastic tube) is inserted into a vein in the subject's arm for collecting blood samples. After the first sample is drawn, the subject takes a dose of efavirenz. Eight more blood samples are collected at 1, 2, 4, 6, 8, 12, 24 and 48 hours after taking the efavirenz tablet. (The catheter is removed after the 12-hour sample and the subject is discharged home, and then returns to the clinic for the 24- and 48-hour samples, which are collected through a needle inserted into an arm vein.) The subject returns to the clinic four more times for a single blood draw at 7, 14, 21 and 28 days after stopping efavirenz. HIV-infected patients whose HIV viral load reaches 1,000 copies/L or more within 12 months after completing the study are asked to return to the clinic for a blood draw to check the genotype of the virus for drug resistance. - Healthy Volunteers - Group 1: Blood samples are drawn to measure efavirenz levels, as follows: Participants take one efavirenz tablet once a day for 13 to 15 days. On the last day of taking efavirenz, the subject takes his/her last dose of efavirenz in clinic, where blood is then collected as described above for HIV-infected individuals. - Healthy Volunteers - Group 2: A catheter is inserted into a vein in the subject's arm and a blood sample is drawn through the catheter. The subject then takes a single bupropion tablet and additional blood samples are drawn at 1,2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 and 48 hours after the dose to measure the amount of drug in the blood. Subjects begin taking efavirenz 0 to 6 days after the last bupropion blood level is measured. As above, subjects will take one efavirenz tablet once a day for 13 to 15 days. On the last day of taking efavirenz, a catheter is inserted into the subject's arm. Two blood samples are drawn through the catheter, the subject takes the daily dose of efavirenz along with a bupropion tablet. Eleven additional blood samples are drawn at 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours after taking the pills to measure blood levels of bupropion. Eight additional samples are collected at 1, 2, 4, 6, 8, 12, 24, and 48 hours to measure efavirenz blood levels. (The catheter is removed after the 12-hour sample and the subject is discharged home; the 24- and 48-hour samples are collected through a needle inserted into an arm vein.)