Fasting and mixed-meal challenges
At CHDR, we use the mixed-meal challenge to study the effects of new drugs on the body’s metabolic response to a typical meal, which includes a combination of macronutrients such as carbohydrates, proteins, and fats. This challenge mimics the physiological process of digestion and nutrient absorption after consuming a normal mixed meal and is particularly useful for investigating drug effects on insulin resistance, glucose tolerance, and overall metabolic function.
Before the challenge, subjects undergo a fasting period. During the challenge, participants are given a controlled meal or liquid formulation containing standardised amounts of macronutrients. We then monitor glucose, insulin, and other metabolic markers over a specified period to evaluate how the body responds to nutrient intake, and how the test compound might influence these responses.
Additionally, we can use indirect calorimetry to measure the energy expenditure and metabolic rate of participants during the challenge. This non-invasive method helps assess how the body processes and utilises energy from the meal, providing valuable insights into the metabolic effects of the test compound. By monitoring oxygen consumption and carbon dioxide production, we can gain a deeper understanding of how drugs impact the body's energy balance and metabolic efficiency in response to nutrient intake.
Glucose-insulin clamping
We use glucose-insulin clamping to assess insulin sensitivity and glucose metabolism in clinical studies. It involves maintaining a stable blood glucose level by infusing insulin and glucose in precise amounts, creating a "clamp" on glucose concentrations.
In a typical clamp study, an intravenous glucose infusion is used to maintain blood glucose at a target level, while insulin is infused at a constant rate. The amount of glucose required to maintain this stable level indicates the subject’s insulin sensitivity. The less glucose needed to maintain the target level, the more insulin sensitive the individual is.
This method is commonly used in clinical research to evaluate the effects of new drugs or treatments on glucose metabolism and insulin resistance, providing valuable insights into metabolic function and the potential for diabetes management.
Gluten challenge
We use gluten challenges to assess the efficacy of new therapeutics in individuals with gluten-related disorders, such as celiac disease or non-celiac gluten sensitivity. In a controlled setting, participants who have been on a gluten-free diet for a certain period are reintroduced to gluten, either through food or a supplement, to observe any physiological or symptomatic responses.
During the challenge, we closely monitor participants for any adverse reactions, such as gastrointestinal symptoms, immune responses, or other related effects. This provides an opportunity to evaluate how new therapeutic agents might mitigate these reactions, offering a comprehensive test of their potential to treat gluten-related disorders. By carefully measuring symptom severity, immune markers, and other biomarkers, we can assess the effectiveness of new treatments aimed at alleviating the adverse effects of gluten consumption.
