Clinical trials

Ketogenic diets are very low-carbohydrate diets that increase hepatic production of ketone bodies, which have several effects as substrates and signals. Ketogenic diets are used to manage some conditions (e.g., drug-resistant epilepsy), and their potential for managing many other conditions (e.g., cancer) is being actively explored. Indeed, the British Dietetic Association acknowledge the potential for ketogenic diets to improve glycaemic control to a greater extent than some other diets in people with type 2 diabetes. A lower fasting glucose is also relevant to future mortality in people without diabetes. Ketogenic diets are popular in the general population, with up to 15% of the UK following a low-carbohydrate diet. There is, therefore, great interest in ketogenic diets amongst people with and without health conditions. However, although the diet shows promising results in improving blood sugar levels, it has also shown to increase low-density lipoprotein-cholesterol (LDL-c) in some individuals, which has been linked to increased cardiovascular health risks. The aim of this project is to find the potential for personalised use of (or guidance to avoid) ketogenic diets for cardiovascular disease risk. To do that the investigators will ask participants to replicate 24 hours of a ketogenic diet and a control diet thrice each. This will allow the investigators to find variability between responses and have a better idea of individuals who could benefit (or not) from following the ketogenic diet.

This project will establish the degree to which adding low-dose galactose to a meal can control blood sugar levels. People will consume standardised glucose drinks (75g glucose, as an oral glucose tolerance test). People will consume these with and without the addition of galactose, and with the addition of another sugar (fructose) for an extra comparison. We will use state-of-the-art labelling methods (dual stable isotope technology) to follow what happens to the glucose that is ingested and understand what happens to sugar being released by the liver and sugar being taken up by other tissues like the muscles. These methods can tell us how the addition of galactose can control blood sugar levels. For example, the galactose could slow down the appearance of glucose from the gut and/or liver released into the blood, or it could increase the disappearance of glucose from the blood into muscles. We will measure the appearance of our label on exhaled breath, which will establish whether ingested sugar is stored, or burned as fuel. We will also explore other potential ways in which galactose might control blood sugar levels by measuring key hormones and metabolites that contribute to blood sugar control (for example, insulin, fatty acids, and incretin hormones which potentiate insulin secretion). This additional evidence of how galactose can control blood sugar levels will provide the understanding required to best make use of this approach across a variety of settings.

Human Physiology is coordinated by a circadian timing system that synchronises daily cycles of light-dark, wake- sleep, activity-rest and feeding-fasting. The alignment of these behavioural patterns with underlying biological rhythms is closely linked to physiological function, with misalignment linked to chronic metabolic diseases. The vast majority of evidence about rhythms in metabolism comes from studies of rodents, which is remarkable given that rodents differ fundamentally from humans in both behaviour and metabolic regulation. Moreover, almost no research in any species has examined the effects of muscle contractile activity on 24-h rhythms in metabolism. Skeletal muscle is a key site of metabolic regulation and contractile activity is a powerful stimulus to increase metabolism. The researchers have established a novel protocol for serial muscle sampling throughout 24 hours and pilot work completed in preparation for this grant revealed diurnal transcriptomic and lipidomic rhythms in human skeletal muscle. Further development of that protocol has used enteral feeding via a tube which delivers nutrient directly to the stomach to enable constant nutrient delivery (including during sleep), with preliminary data indicating that underlying rhythms in metabolism are responsive to nutrient availability patterns. The researchers will now capitalise on those findings by incorporating multiple isotope tracers within the protocol, thus finally documenting the nature of rhythmic flux in carbohydrate metabolism and protein turnover in human skeletal muscle, and how those rhythms are aligned with timing and patterns of exercise. In summary, participants will stay in the laboratory for 36 hours with 24 hours of constant feeding via nasogastric tube, and muscle and blood sampling. Participants will be allocated to either the early or late exercise group (involving 1 hour of cycling at either 0800 or 2000 h, respectively) or the control group who will rest for the 24 hours.

Inadequate plant food intake is a leading modifiable risk factor for non-communicable disease. However, on average, 88% of individuals do not consume adequate amounts of vegetables. Using digital technology may help improve health behaviours , with this potentially providing an accessible route to increasing plant food intake. However, uptake and engagement with applications designed to influence health behaviours is generally poor , and few studies have examined the main factors supporting user engagement and retention. Personalised dietary feedback, such as the provision of personalised advice or recipes, has the potential to enhance this process. However, whether nutritional interventions utilising personalised dietary feedback support user interaction, engagement, and retention remains to be studied. Hence, the proposed project is a proof-of-concept study aiming to assess the effectiveness of using an application with personalised dietary feedback to support increased healthy plant food intake. 315 healthy males and females, between the ages of 18- and 45-years who self-report less than 50% of the recommended intake of vegetable consumption will participate in the study. Before the intervention, participants will receive web-based instruction on the use of the smartphone application. Subsequently, participants will log all meals for two-weeks using the application to generate a baseline plant food consumption profile. In the baseline period, participants will wear a continuous glucose monitor. This will inform their individualised goals and possible feedback for the intervention period. The intervention will be 4-weeks in duration, consisting of the use of a personalised dietary program application, which will provide both recipes and feedback. Those randomised to the control will only have access to the meal logging feature. Throughout this period, participants will wear a smartwatch to track sleep metrics such as sleep onset and duration. Following the four-week intervention period, participants will be able to continue using the app for a six-week period, during which engagement with the application over time will be ascertained via telemetry. At the end of the follow-up, participants will receive an exit questionnaire to provide insight on their experience with the application, attitudes, habits and knowledge regarding consumption of plant foods, and self-perceived impact on health and dietary habits. To provide mechanistic insight, a subset of participants (n = 50) will visit the laboratory at the University of Bath on two occasions (approximately 45 minutes each) - baseline and post-intervention. During laboratory visits, participants will provide blood pressure and body weight measurements, as well as saliva and venous blood samples. Saliva samples will be assessed for salivary cortisol, and blood samples will be assessed for the following: plasma glucose \& insulin; plasma uric acid; plasma ascorbic acid; plasma tocopherols; serum carotenoids; plasma cytokines; plasma CRP and ferritin; F2-Isoprostanes; immune cell inflammatory capacity; HbA1c.

Eccentric exercise, particularly when novel and strenuous, can cause soreness and inflammation, impairing subsequent exercise performance. These performance decrements are attributable to oxidative stress and inflammation. Interestingly, a single bout of eccentric exercise can confer protective effects, ameliorating the negative consequences in subsequent bouts. This is termed the repeated bout effect (RBE), which would be of interest to athletes considering the detrimental effects of strenuous eccentric exercise. Athletes regularly consume supplements in hope of attenuating the performance decrements after strenuous eccentric exercise . However, considering the dose-response relationship between the initial performance decrement and the magnitude of the RBE , supplements may diminish the obtainment of the RBE. This notion remains untested, and so the proposed project is a double-blind, placebo-controlled, parallel group study aiming to assess the effects of acute vitamin C and ibuprofen supplementation on the development of the RBE. These two supplements were chosen as they are most frequently and successfully used in the literature to target oxidative stress (vitamin C) and inflammation (ibuprofen). Additionally, these doses (and the timing of supplements) were chosen to mimic protocols reporting beneficial effects

The aim of this pilot study is to estimate the effect size of changing the glucose-fructose ratio from 1:0.5 to 1:1 on exogenous carbohydrate oxidation rates during exercise, which can be used to power a future definitive study.

Recent research has suggested that increasing levels of physical activity are associated with a reduction in the independent components that contribute to total energy expenditure (such as resting metabolic rate and non-exercise movement) - this occurs to conserve energy required for physical activity where energy provision becomes scarce. There are potential deleterious health and performance consequences of a reduced energy supply to fundamental metabolic processes, putting individuals regularly undertaking high levels of physical activity, such as endurance athletes, at risk. However, this association is largely based on observational data in only moderately active populations, and it is currently unclear what role energy balance status and biological sex has on this relationship. This research intends to address these unknowns by assessing the impact of diet-induced manipulation of energy balance (conditions of energy deficit and energy surplus) in individuals undertaking habitually high levels of physical activity on independent components of total energy expenditure (resting metabolism, exercise and non-exercise movement). Male and female athletes conducting regular moderate-to-high training volumes will undertake a randomised crossover study with a 7-day state of energy deficit and a 7-day state of energy surplus. Participants will continue to live and train as normal, but their diet will be controlled by specific food provision over the intervention periods in order to facilitate both conditions. Independent components of energy expenditure, markers of health, metabolism and performance will be measured to allow for comparison of conditions.

Overall aim: To identify the impact and acceptability of a novel method of neuromuscular electrical stimulation (NMES) for improving glucose control using a dual stable isotope tracer OGTT in individuals with spinal cord injury (SCI). Objective 1: 1. To establish the extent to which an acute bout of NMES improves health-related measures of glucose control, compared to a SHAM control trial. 2. To identify the relative magnitude of effect, compared to non-injured control participants (CON). Hypotheses: 1. NMES will be more effective at improving glucose control by increasing peripheral glucose uptake, relative to SHAM condition. 2. The effect will be greater in individuals with SCI compared to non-injured control participants. Objective 2: To investigate the real-world feasibility of NMES as a therapeutic intervention, participants with SCI will be given instructions for 2-weeks of at-home use. In-depth interviews will be conducted to evaluate acceptability and identify areas that could be adapted to effectively implement NMES in a future trial. Participants will complete two experimental trials in a randomised crossover fashion separated by 7 days which will consist of either a sham control (SHAM) or an acute bout of NMES during a 3-h oral glucose tolerance test (OGTT). Following the experimental trial days, participants with SCI will take home a NMES device and will be given instructions for 2-weeks of at-home NMES use (Figure 1) to assess acceptability and feasibility.

With advances in genetic therapies, many people with Cystic Fibrosis (CF) are living longer. With the improvement in life expectancy has emerged an increased risk of cardiovascular disease (CVD). Factors such as insulin resistance, reduced physical activity, rising blood pressure from newer medications, and changes in body mass index have made cardiovascular health a growing concern in CF care. This study aims to assess whether a remotely delivered, monitored exercise programme can increase physical activity levels in adults with CF. Secondary outcomes will explore whether the intervention improves key CVD risk factors. Participants will be randomly assigned to either a control group or an intervention group, which will complete an 8-week home-based aerobic and resistance exercise programme. Exercise intensity will be tailored using the Rate of Perceived Exertion scale. Key outcomes include weekly physical activity levels, body mass index, waist circumference, lung function (spirometry) and blood biomarkers. Home-based capillary blood tests, analysed pre- and post-intervention, will measure cholesterol, lipid profiles, inflammation and other relevant hormones.

Axial spondyloarthritis (axSpA) is an autoimmune disease that causes inflammatory arthritis of the spine, causing pain, stiffness, and mobility limitations. During flares, when symptoms worsen, people with axSpA often experience increased pain and difficulty moving, making daily activities more challenging. This study aims to explore whether virtual reality (VR) exercise can help manage pain, improve movement, and support rehabilitation for axSpA patients during flares. Participants will use a VR system to perform gentle exercises designed to encourage movement and reduce discomfort. Their spinal mobility will be measured using motion capture technology, and their experiences with VR will be assessed through questionnaires and interviews. This research will help determine whether VR can be a practical and beneficial tool for axSpA rehabilitation, potentially offering a new way to manage symptoms and improve quality of life. The findings will guide future studies on using VR in healthcare settings for people with chronic pain conditions.

Metabolic conditions, such as heart disease, type 2 diabetes, and metabolic syndrome, are among the leading causes of disability and mortality worldwide. Identifying innovative lifestyle strategies to reduce metabolic risk remains a public health priority. Further research is essential to understand how low carbohydrate intake influences human metabolism and how intermittent carbohydrate restriction impacts weight loss and metabolic health markers. This study will investigate two interventions that restrict dietary carbohydrate intake on different schedules, examining their effects on metabolic health and energy balance in adults with abdominal overweight or obesity. The physiological mechanisms potentially underlying these effects will be explored by measuring a range of lifestyle and metabolic health parameters in both free-living and laboratory settings. A digital behaviour-change intervention will be incorporated after the dietary intervention to assess whether any metabolic effects can be sustained over time. The study employs a three-arm parallel-group design consisting of a two-week lifestyle monitoring phase, a four-week dietary intervention, and a four-week digital intervention, with four laboratory visits throughout each phase. During the dietary intervention, participants will be allocated to one of three groups: (i) carbohydrate restriction (\<8% of energy intake) on two consecutive days per week, (ii) carbohydrate restriction after 4 pm each day, or (iii) no dietary changes. Dietary intake, physical activity, and glucose levels will be monitored through wearable devices in free-living conditions. The digital intervention will use a mobile health application that provides individualised lifestyle recommendations and education based on data collected in free-living conditions. Laboratory-based measures will include anthropometry, body composition scans, indirect calorimetry, blood pressure monitoring, fat biopsies, and postprandial sampling of blood and expired air.

Compassion is recognising that someone is suffering and wanting to help them. Compassion fatigue is a reduction in capacity to feel compassion for others. Secondary trauma is the experience of traumatic responses to hearing about someone else's trauma. Burnout is depersonalisation, emotional exhaustion, and feeling less good at one's job. Compassion fatigue, secondary trauma and burnout can all be referred to as empathy-based stress. This is a problem for healthcare staff and their patients. Staff experiencing empathy-based stress deliver less high quality care, which can lead to serious consequences for patients. Empathy-based stress is also associated with staff sickness, which is bad for staff and costly to the United Kingdom's National Health Service (NHS). Child and adolescent mental health (CAMHS) wards are busy, high-pressure environments where families and young people are often upset, resources are stretched, and staff are managing high levels of patient risk of self-harm or suicide. The principal investigator has already reviewed research on empathy-based stress and interventions to prevent and/or reduce it in mental health ward staff. This evidence has been presented to CAMHS ward staff, managers, commissioners, patients and families and these stakeholders have co-designed an intervention for wards, to reduce empathy-based stress. The intervention aims to help staff to feel better and care better. This pilot study aims to test and improve our intervention on two CAMHS wards, measuring how useful and well-liked it is, and how feasible it would be to use it and to test it on more wards. Staff on CAMHS wards will be offered a modular intervention including psychoeducation about empathy based stress and ways of combatting it, and workplace stressor and management toolkits. NHS CAMHS ward staff and patients will be asked to complete questionnaires and a subsample of staff will be asked to complete interviews about the process of the intervention.