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176 active trials for Inflammation

Impact of Acute and Chronic Inflammation on Cytochromes P450 Activity Measured With Dried Blood Spot

Cytochromes P450, main enzymes of drug metabolism, play a prominent role in the first-pass metabolism of oral substances. Inter-individual variability in their activity due to genetic and environmental factors has been observed and may be associated with adverse therapeutic outcomes (ineffectiveness or toxicity). The inflammation, whether acute or chronic, can theoretically modulate the pharmacokinetics of drugs by modulating enzyme activity. Indeed, in vitro data and animal models, as well as more limited data in humans, indicate a down-regulation of CYP in the context of inflammation. The cocktail approach developed and validated in Geneva ("cocktail Geneva") measures the activity of several CYP simultaneously using micro-doses of probe drugs and facilitating sampling (10uL capillary blood) on a dried blood spot. We intend to measure the activity of CYP in an acute inflammation model (hip surgery and SARS-CoV-2 infection) and chronic inflammation (rheumatoid arthritis, RA). The effect of the biological agent tocilizumab (anti IL-6 receptor) in a treated patient subgroup (patients treated regardless of our study) will be measured after 3 months of treatment. The main objective is to determine if interleukin 6 levels are correlated with the activity of CYP450 in patients with acute (orthopedic surgery - hip or SARS-CoV-2 infection) or chronic inflammation (RA). Secondary objectives are: To correlate CYPs activities with the levels of other inflammatory markers (CRP, TNF-?, IL-1?, IFN-?); To assess correlation between markers of inflammation, CYP activities and the intensity of fatigue and pain; To assess if tocilizumab reverse CYP activity in patients with RA after 3 months treatment; To assess if SARS-CoV-2 infection modify pharmacokinetic parameters of concomitant medications which are CYPs substrates

Start: September 2017
Dietary Nitrate, Vascular Function and Inflammation

The risk for cardiovascular diseases (CVD) increases with advancing age. Developing effective lifestyle-based strategies to promote, preserve or restore cardiovascular health with aging is a high priority. The overall aim of this clinical research is to investigate the innovative concept that an increased intake of dietary nitrate (through beetroot juice) could be a feasible adjuvant therapy to treat elevated blood pressure and improve blood vessel function in older adults. Inorganic dietary nitrate, found in beetroot and green leafy vegetables, is a source of nitric oxide (NO), a signaling molecule that is important for cardiovascular health. NO is also produced in the human body, but the body's production and availability of NO decrease during ageing and CVD. The declined NO availability is associated with impaired blood vessel function, unresolved inflammatory responses, and an increased CVD risk. Dietary nitrate is an additional NO source. Following the intake of nitrate, NO is produced in a pathway that involves commensal bacteria in the mouth. So far, little is known about whether dietary nitrate improves cardiovascular health in older populations with high blood pressure. The aim of this randomized, placebo-controlled crossover study is to investigate whether the daily intake of nitrate-rich beetroot juice over four weeks translates into improved cardiovascular health-related outcomes in older adults with treated mild high blood pressure. Men and women, between the ages of 55 and 70 years, who have been diagnosed with grade 1 high blood pressure and who are taking two or more blood-pressure lowering medications will be recruited. The study will investigate whether the increased dietary nitrate intake further lowers blood pressure and improves blood vessel function. A specific aim is to examine whether the nitrate intake results in favorable changes in the oral bacteria community and the systemic inflammatory status, and whether these changes correlate with cardiovascular-related outcomes. This research will offer information on the value of dietary nitrate to counteract chronic inflammation, the latter of which plays a role in developing or worsening cardiovascular disorders, such as high blood pressure. The expected results of this study will provide important new evidence of whether nitrate-rich beetroot juice could be a key component of therapeutic interventions to improve cardiovascular health in individuals with high blood pressure.

Start: January 2021
Intermittent Fasting and CLL/SLL

What are the investigators trying to do? By most measures, humans consume more food than needed. Over several decades, overconsumption has led to an increase in a number of diseases, including cancer. What if this could be reversed, or slowed down, by fasting? Would that improve how cancer patients respond to chemotherapy? Could simply changing eating patterns to reduce overall intake be a way to prevent and/or manage cancer? All of these are important questions and the investigators are undertaking a new initiative to study how nutrition and dietary behaviours affect cancer patients. Fasting: A way to improve overall health and increase our defenses to cancer Fasting in various forms has been shown to have a number of health benefits. Intermittent fasting, or time restricted feeding, has been shown to reverse or improve various diseases such as diabetes, heart disease and metabolic syndrome, decrease the risk of cancer, and significantly extend the life of an individual. In previous studies, fasting was well-tolerated with notable improvements in energy levels, sense of well-being, and sleep quality. In cancer patients, clinical trials have demonstrated intermittent fasting to lessen some of the short-term side effects of chemotherapy such as nausea, fatigue, and sleep quality. How fasting alters the course of cancer or improve immune defenses is not yet known but may be an alternative way to treat or manage cancer. The study plan The investigators plan to examine the effects of intermittent fasting (time restricted feeding) in patients with chronic lymphocytic leukemia (CLL). CLL is the most common chronic leukemia and is presently incurable. The advantage of choosing this patient population is that the cancer is easily assessed with a blood test measuring the amount of cancerous white cells (lymphocytes). Patients who consent to participate in this study will, through the support of an oncology dietitian and after a period of transition, split their daily feeding into a fasting period and a non-fasting period. This regime is as simple as skipping or having a late breakfast. At this time, participants will not be required to limit their total caloric intake. What is required from the participant? The investigators will assess whether intermittent fasting reduces the cancer by measuring the lymphocyte count in the blood over a period of 3 months. Study participants will complete questionnaires to help determine if fasting causes any change in their quality of life. The effects of intermittent fasting on a cancer control system called autophagy, as well as its effects on inflammation will be studied in the Deeley Research Centre laboratory at BC Cancer. What is the short- and long-term impact? In the short-term, if intermittent fasting can have an effect cancer lymphocyte count or on autophagy, then investigators will proceed with further studies to try and optimize the effects of intermittent fasting. In the long-term, this study is expected to be the first-ever to shed light on how intermittent fasting may be linked to cancer survival and/or growth. If true, this will open up new avenues to re-evaluate the inclusion of diet into cancer treatment protocols.

Start: February 2021