Active clinical trials for "Inflammation"

Several free fatty acids receptors (FFARs) have been discovered. These have been implicated in metabolic processes and inflammation. Consequently, these receptors have attracted interest as targets for the treatment of metabolic and inflammatory diseases, including obesity and T2D. Two of these FFARs (FFAR1, FFAR4), which is activated by specific free fatty acids (FFAs), is expressed on enteroendocrine cells, pancreatic beta-cells and adipocytes. They have been linked to 1) increased GLP-1 secretion and hence the incretin-mediated increase in glucose-stimulated insulin secretion (GSIS) and suppression of glucagon secretion, 2) a direct positive effect on GSIS, 3) reduced inflammation and 4) improved insulin sensitivity. These functions and the abundance of fatty acids in food suggests that FFARs can be considered as nutrient sensing regulators of metabolism. Roux-en-Y gastric bypass (RYGB), frequently results in immediate beneficial effects on glucose metabolism and often complete remission of T2D. This may in part be explained by increased GLP-1 levels after surgery. It appears that the effect depends on nutrient delivery directly to the lower parts of the small intestine. It is possible that the RYGB effects are partly due to enteroendocrine stimulation of FFAR1 and perhaps FFAR4 by direct nutrient delivery, i.e. FFA release in the lower intestines. Pinolenic acid from pine nuts has been shown to be a potent dual FFAR1/FFAR4 agonist. Based on these findings the investigators have planned a number of human intervention studies in order to investigate 1) the optimal oral formulation of pine nut oil 2) whether it is possible to mimic the beneficial effects observed after RYGB, 2) if it is possible to increase meal-related GLP-1 secretion by stimulating FFAR1/FFAR4 on enteroendocrine cells causing improved GSIS and increased satiety and 3) enhancement of GSIS by directly stimulating FFAR1 (and perhaps FFAR4) on beta-cells.

The improvement of maternal and child health remains a key issue in global health. Production and improved accessibility of healthy and nutrient-rich milk-based products could potentially tackle health and nutrition inequalities in low-income countries. This study will assess the acceptability of a multi-component intervention, including provision of calcium/vitamin-D fortified milk and periodontal therapy (PT), for improving maternal periodontal health and metabolic and inflammatory profiles. The IMPROVE trial is a feasibility randomised controlled trial (RCT) with parallel qualitative process evaluation. The target population is low-income, pregnant, Brazilian women, with periodontitis, who have not seen a dentist in the last 6 months. A series of focus group discussions and interviews with the target population will be conducted to identify key barriers and enablers to adoption and implementation of the intervention in prenatal clinics in Rio de Janeiro/Brazil. Participants will be allocated to 4 groups: 1) early PT (during pregnancy) plus fortified milk; 2) early PT plus plain milk; 3) delayed PT (after delivery) plus fortified milk; 4) delayed PT plus plain milk. The final results will contribute to the understanding of the significance of calcium and vitamin D for short and long-term health and the occurrence of diseases, as well as to inform the current global debate on vitamin-D supplementation and fortification policy.

Open heart surgery requires the use of a cardiopulmonary bypass (CPB) circuit. As blood flows across the artificial surfaces of the CPB circuit, platelets are activated and consumed. This activation results in a profound inflammatory reaction and need for transfusion. This reaction is intensified in younger, smaller patients undergoing longer, more complex open heart surgery. Nitric oxide is naturally released by vascular endothelial surfaces and acts as a signaling molecule which prevents platelet activation. The investigators hypothesize that the addition of the nitric oxide to the sweep gas of the oxygenator during cardiopulmonary bypass surgery will replace this natural endothelial function and thus prevent platelet activation and consumption. The investigators plan to test this hypothesis with a pilot double blinded, randomized trial of 40 patients less than a year of age undergoing cardiac surgery requiring CPB.

The aim of this study is to determining of the effects of Eicosapentaenoic acid (EPA) supplementation on serum activities of Paraoxonase-1 and Homocystein thiolactonase, and serum levels of some indicators of vascular inflammation, and the gene expression of PON2 in the peripheral blood mononuclear cell (PBMC) in the patients with type II diabetes mellitus.

By 2030 an estimated 2 million people in the US will need dialysis or transplantation for advanced kidney failure. An even more disturbing statistic is that mortality in End Stage Renal Disease (ESRD) is six times higher than in the general Medicare population with adjustment for age, gender and ethnicity. Protein energy wasting is highly prevalent in these patients and is one of the most important determinants of their poor clinical outcome. Despite its well-recognized occurrence, the etiology and the mechanisms leading to protein energy wasting observed in chronic hemodialysis patients cannot be attributed to any single factor. However, irrespective of the specific etiologic mechanisms, it appears that the common pathway for all the metabolic derangements is related to exaggerated protein degradation relative to protein synthesis (47). Two well-recognized and presumably interrelated metabolic abnormalities, insulin resistance and chronic inflammation, may be the major determinants of protein catabolism in coronary heart disease (CHD) patients. There are no studies examining the effects of anti-inflammatory interventions and/or insulin sensitizers on protein homeostasis in CHD. Due to their established anti-inflammatory and other pleiotropic effects, Interleukin-1 receptor antagonist Anakinra and insulin sensitizer peroxisome proliferator-activated receptors (PPAR) agonist Actos represent two such promising interventions. By modulating inflammatory response and insulin signaling through two pharmacological interventions, the investigators will have the unique opportunity to clarify mechanisms contributing of these two particular metabolic derangements in the development of protein energy wasting observed in chronic hemodialysis patients. The overall goal is to elucidate the mechanisms by which chronic inflammation and insulin resistance influence the development of protein energy wasting in hemodialysis patients. Specific Aim: To test the hypothesis that inhibiting inflammatory response by administration of an Interleukin1receptor antagonist (Anakinra) or increasing insulin sensitivity by administration of a PPAR agonist (Actos) will improve net protein metabolism. Hypothesis: The chronic inflammatory component of protein energy wasting (PEW) observed in hemodialysis patients is, at least in part, mediated by insulin resistance. Interim analysis may be performed (no specific plan at this time).

The purpose of this study is to evaluate the effects of IL-1β inhibition on safety, measures of systemic and vascular inflammation and endothelial function (all indicators of cardiovascular risk) in treated and suppressed HIV infected individuals This study will assess the safety and effects of canakinumab on endothelial function (assessed by flow-mediated vasodilation [FMD] of the brachial artery), vascular inflammation (assessed by FDG-PET/CT scanning), key inflammatory markers of cardiovascular disease (CVD) risk (high-sensitivity C-reactive protein [hsCRP]), interleukin-6 (IL-6), soluble CD163 (sCD163), D-dimer, T-cell and monocyte activation in the blood, and size of the HIV reservoir. 10 individuals will receive a single dose of 150mg canakinumab with follow-up for 12 weeks. In the second part of the study, 100 participants will be randomized (2:1 - canakinumab to placebo) and will be followed by for 36 weeks.

Background: Subacromial impingement syndrome (SIS) is a chronic and disabling disease, characterized by compression and mechanical abrasion of the tendons of the rotator cuff muscles, subacromial bursa and tendon of the long head of the biceps against the anterior surface of the acromion, coracoacromial ligament or the acromioclavicular joint during arm elevation movement. After the trauma, inflammatory processes initiate and may lead to loss of function when untreated. This inflammation leads the release of cytokines (IL-6, IL-10, IL-1β and TNF-α) whose acts as inflammatory mediators. Physical therapy works in treating SIS with the goal of reducing pain and inflammatory process. Cryotherapy is widely used in physical therapy by anti-inflammatory and analgesic effects, low cost, effectiveness and easy application. Objective: The aim of the study is to evaluate the effects of a cryotherapy protocol, applied on shoulder of subjects with SIS, on serum inflammatory mediators (cytokines) and local pressure pain threshold. Possible changes in function and pain will also be evaluated. Materials and Methods: 30 subjects will be selected and share in two groups, 15 healthy subjects and 15 subjects with SIS. Function assessments and quality of life will be held using the DASH and WORC questionnaires. Cryotherapy will be applied for 4 consecutive days, lasting 20 minutes without interruption through ice pack over the shoulder of SIS carriers. For the blood samples, 20ml of blood will be collected at the first and last day of the intervention, and then stored at -80 ° C.

Background: In recent years, the prevalence of both asthma and obesity has risen dramatically among children and adolescents in the United States. Given the concurrent rise in the two epidemics, there may be an underlying link. Obesity contributes to asthma severity and control, and may play a role in its underlying cause. Obesity is associated with a state of heightened inflammation that may lead to an increase asthma symptoms and severity. Obese adult patients treated with montelukast, an anti-inflammatory agent, seemed to have better asthma control than those treated with other standard asthma medications. The use of montelukast in obese children and adolescents has not been specifically studied. Hypotheses and Specific Aims: The use of montelukast will improve asthma symptoms and objective markers of asthma to a greater degree in obese, as opposed to non-obese children and adolescents. The investigators would like to determine if the use of montelukast will improve objective asthma scores, pulmonary function, markers of inflammation and medication use to a greater degree in obese as opposed to non-obese children/adolescents. Potential Impact: Given the growing epidemic of obesity-associated asthma in the U.S., a tailored approach focused on obese asthmatic children may help reduce the burden of this disease, health care costs and potential long-term complications as these children enter adulthood. Furthermore, this study may help clarify the underlying mechanisms that link asthma and obesity. Although this proposal is focused on one medication, it provides an example of how certain medications may have differential efficacy in the obese asthmatic.

Cysteinyl leukotrienes (cys-LTs) are lipid inflammatory mediators that abound in mucosal inflammation and play a validated role in the pathogenesis of human asthma. It has recently been demonstrated that the platelet adenosine diphosphate (ADP) receptor, P2Y12, is required for LT4-mediated pulmonary inflammation and could be a novel potential therapeutic target for asthma. Thienopyridines (such as ticlopidine and clopidogrel) are pro-drugs, with proven antithrombotic efficacy, whose active metabolites selectively inhibit the platelet P2Y12 receptors. One of the drawbacks of thienopyridines is the high inter-individual variability in pharmacological response, mostly due to the high inter-individual variability in the capacity of transforming the pro-drug in its active metabolite. Prasugrel is a new member of the class of thienopyridines, with faster onset of action and a more uniform inhibition of platelet function compared to the other thienopyridines. Primary objective of our study will be to test whether or not the inhibition of the platelet P2Y12 receptor by prasugrel reduces the bronchial hyper-reactivity in patients with chronic asthma. The investigators designed a randomized, double blind (Subject, Caregiver, Investigator, Outcomes Assessor), crossover, placebo-controlled, prospective study, which will enroll 26 patients. Randomization will be performed in sequential blocks. Patients will be blindly and randomly allocated to treatment A (prasugrel 10 mg daily) or B (placebo) for 15 days. After a 15-day wash-out period, patients who had initially been allocated to treatment "A" will be allocated to treatment "B", and vice versa. Measurements will be done at baseline and on day 15 after each treatment, at the same time (+/- 1 h) of the day. Primary efficacy measure will be changes in airway hyper-responsiveness, recorded as reduction of FEV1 using the mannitol test induction. Secondary efficacy measures will be changes in markers of airway inflammation in sputum, changes in measurement of nitric oxide expiration (as surrogate marker of airway lung inflammation), count of eosinophil granulocytes in peripheral blood smear, changes in asthma exacerbation rates and symptom scores. Changes in phosphorylation of platelet VASP (Vasodilator-stimulated phosphoprotein) by ADP, measured with a flow cytometric technique, will be used as markers of the degree of inhibition of platelet P2Y12 receptors attained in each subjects by treatment with prasugrel.

This trial is conducted in Europe. The aim of this trial is to evaluate the change in disease activity following 12 weekly s.c. (under the skin) doses of NNC109-0012 compared to placebo in subjects with active Rheumatoid Arthritis (RA).