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This study will assess the dose-response effects of Inspiratory Muscle Strength Training (IMST) in adults with above-normal systolic blood pressure over a 6-week period.
For this protocol, the investigators plan to collect data to evaluate apremilast (60mg/day or 90mg/day) vs placebo in adults with Alcohol Use Disorders (AUD).
The purpose of the study is to determine how blood sugar levels in individuals with and without hypoglycemia after bariatric surgery respond to different doses of glucagon, a hormone that is usually present in your body that regulates blood sugar levels. In this study, there will be 4 visits to the clinical research center. In the first visit, medical history and physical exam will be performed, and blood samples will be taken to assess overall health. During visit 2, a continuous glucose monitor will be placed under the skin. (This may be combined with visit 1, depending on the schedule of visits.) In visit 3, we will test the effect of a total of 4 different doses of glucagon, in increasing doses. In visit 4, we will test the effect of a total of 3 doses of glucagon, in decreasing doses. For both visit 3 and 4, we will infuse labeled stable glucose to allow us to measure how much glucose the body is making, and will measure levels of hormones which regulate glucose, such as insulin and glucagon.
The purpose of the study is to see examine the effects of 3 different levels of physical activity (45 minutes/week, 90 minutes/week, or 150 minutes/week) on arthritis symptoms.
The purpose of this study is to evaluate the dose-dependent effects of glucosyl-hesperidin (CITRAPEAK) supplementation on exercise performance, recovery indicators, blood flow, cognitive function, mood, sleep, and fuel utilization in recreationally active adults.
The study is a randomized, double blind, placebo-controlled, dose response, phase II, multicentre trial to evaluate the efficacy and safety of oral AP1189 administered at the doses of 40, 70, or 100 mg for 12 weeks in combination with methotrexate, in DMARD-naïve participants with early rheumatoid arthritis and active inflammation.
The development of efficacious medications for AUD remains a high research priority with current emphases on identifying novel molecular targets and efficiently screening new compounds. Pharmacological modulation of the kynurenine pathway (KP) represents a promising novel target for AUD. The KP is a complex enzymatic cascade with each step producing biologically active metabolites that are critically involved in diverse physiological and pathological processes. Chronic alcohol exposure produces dysregulation of the KP, particularly as evidenced by decreased levels of the neuroprotective metabolite kynurenic acid (KYNA) and increased levels of the neurotoxic metabolite quinolinic acid (QUIN). This metabolic shift is associated with various alcohol-related pathologies in animals and humans. Thus, a medication that targets the KP to restore KYNA and attenuate QUIN levels may be an effective treatment for AUD. The enzyme kynurenine 3- monooxygenase (KMO) is a major gatekeeper of the KP and resultant KYNA levels. KMO inhibition shifts the KP towards KYNA production in brain and away from QUIN production. Critically, KMO inhibition in rodents, through its increase in brain KYNA levels, decreases alcohol self-administration, preference, cue-reactivity, and relapse behaviors. However, KMO-inhibitors have not been tested in humans because of presumed lack of availability. Diclofenac is an FDA-approved Non-Steroidal Anti-Inflammatory Drug that was recently discovered to inhibit KMO activity. Consistent with KMO inhibition, diclofenac increases KYNA levels in the brain and periphery of rodents. However, it remains unknown whether diclofenac increases KYNA levels and affects alcohol-related behaviors in humans at approved, safe dosages. Investigators propose to conduct a human laboratory pilot study to test whether diclofenac can increase KYNA in individuals with AUD, and if so, which of 3 doses (50, 75, or 100 mg) most effectively increases KYNA. Individuals with AUD (n = 24) will complete four sessions where they receive diclofenac (50, 75, or 100 mg) or placebo. Investigators will examine increases in KYA levels and will also assess QUIN levels, alcohol craving, and negative mood.
A large body of evidence indicates numerous health benefits of physical activity, including prevention of cardiovascular disease (CVD), the leading cause of death in the US. This evidence has led to US Physical Activity Guidelines that recommend ≥150 min/week of moderate or ≥75 min/week of vigorous aerobic exercise (AE), plus resistance exercise (RE; such as weight lifting) on ≥2 days/week. To date, current research has mostly focused on AE, and we know a great deal about the dose-response relation between AE and health, resulting in clear and practical guidance to the public on the recommended "dose" in min/week. However, currently far less is known about the dose-response for RE: ≥2 days/week are recommended, but with no duration specified. Thus, this project aims to provide clarity on the dose relationship between RE and health. This project will significantly contribute to developing more effective CVD prevention approaches, advancing prescriptive intervention guidelines, by helping to fill the important gaps in knowledge on effective minimum dose, beneficial optimal dose, and safe maximum dose of RE for CVD prevention. Thus, advancing prescriptive intervention guidelines, and provide important insights for future science of physical activity and health.
Parabolic flight provides a unique opportunity to evaluate the acute changes associated with varying levels of gravity and to describe how key venous parameters change at levels less than normal Earth gravity. Characterizing these changes in response to varying G-levels is an important step in determining what G-level may be required to reverse weightlessness-induced fluid shifts and thus serve as a viable countermeasure during long-duration spaceflight. Further, these results will inform National Aeronautics and Space Administration (NASA) whether there might be a lower risk of Spaceflight Associated Neuro-ocular Syndrome (SANS) and Venous Thromboembolism (VTE) during extended stays on the Moon and Mars.
The present study aims to address gaps in the literature by evaluating the objectively measured dose-response relationship between exercise and depression symptoms; examining changes in resting (Brain-derived Neurotrophic Factor) BDNF from baseline to week 10 of an exercise intervention; and assessing varying exercise intensities on enjoyment, affect, and health-related quality of life in sedentary young adult college students.