Clinical trials

Cystic fibrosis (CF) is an inherited condition that affects several organs, including the gut. People with CF often experience uncomfortable digestive symptoms such as bloating, gas, abdominal pain, and constipation. The root cause is that the gut produces thicker-than-normal mucus, which slows things down and makes it harder for the bowel to work properly. Current treatments such as laxatives, enemas, or surgery can be inconvenient and don't always work well. There is a real need for better options, and for a clearer understanding of how the CF gut behaves and responds to treatment. This study will use MRI, a non-invasive imaging technique, to look at how fluid moves through the gut in adults with CF and the impact of linaclotide. Linaclotide is a licensed medication used to treat chronic constipation and irritable bowel syndrome. It works by encouraging the gut to release more fluid, helping things move more easily. It acts locally in the gut and is not absorbed into the bloodstream. Early research suggests it may help in CF in a way that does not rely on correcting the underlying genetic fault, making it a promising avenue to explore. Participants will include people with different bowel habits, including those who tend towards constipation and those who tend towards diarrhoea. The scans will help researchers check whether certain MRI measurements can reliably detect changes in gut fluid and movement. This is a feasibility study; its main objective is to test whether these MRI measurements are useful and practical, and support a sample size calculation, in future CF studies investigating linaclotide effects.

The goal of this study is to establish if non-invasive closed-loop neuromodulation is an effective approach to enhance cognitive function in healthy 18-40 years old volunteers. The main questions it aims to answer are: * Can closed-loop stimulation increase stimulation effectiveness? * Can closed-loop focused ultrasound specifically engage with excitatory or inhibitory neural populations in the target structure as measured through MRS? * Can observed stimulation outcomes for FUS be predicted through connectome analysis and computational models of indirect changes? Researchers will compare different closed-loop options to their open-loop counterpart to see if closed-loop approaches can increase efficacy and reduce the variability of the stimulation compared to open-loop approaches. Participants will: * Answer some questionnaires at the start of the study and after each intervention session. * Undertake a MRI scanning session. * Undertake one open-loop FUS session. * Undertake one tES session. * Undertake one closed-loop FUS sessions involving tES and FUS, followed by a MRI scanning * Undertake one sham FUS session * Attend one visit in person to assess eligibility through questionnaires and one cognitive task

Colorectal cancer is the fourth most common cancer in the UK. Prehabilitation, including exercise, can improve recovery from surgery. This pilot study investigates the combined effects of resistance and high-intensity interval training (ReHIIT) in healthy adults to establish baseline physiology and responses for comparison with cancer patients

The Lived Experience Narratives in Dementia (LEND) research programme involves five work packages (WP). WP1 explores how people living with dementia use narratives and how narratives can impact them. Findings will support the development of LEND theory. WP 2-3 focus on developing the digital Online LEND Intervention, assessing its usability and acceptability, and conducting a feasibility study within NHS memory assessment and community services. Activities across the first three WPs include interviews, focus groups, user-testing sessions, engagement evaluation interviews, and a two-arm randomised feasibility trial using a range of outcome measures. Findings from this stage will inform refinement of the intervention and determine the feasibility of progressing to a future randomised controlled trial (RCT) of the Online LEND Intervention. WP4 is the Online LEND Intervention two-arm RCT. WP5 involves dissemination. The protocol for WP4 and 5 have not yet been developed and rely on results from WP1-3.

The goal of this study is to learn about people's experiences of how physiotherapy is received having recently had surgery for a broken ankle. The ways to receive the rehabilitation will be via video, call Early Virtual Ankle Rehabilitation (EVAR), and face-to-face at the hospital. The content of the rehabilitation programme will be the same for both groups. The main questions that the study aims to answer are: * During the early weeks of recovery after ankle surgery, how happy are people to have physiotherapy support by video call (EVAR) compared with face-to-face appointments at the hospital? * Is it practical to run a larger study on how well EVAR helps recovery from ankle fracture surgery? Participants will be put into one of two groups by chance: * A group that has EVAR, with physiotherapy appointments by video call to their home. * A group that has face-to-face physiotherapy appointments at the hospital. All participants will receive the same early physiotherapy programme. The only difference between the groups is how physiotherapy support is received. Participants in both groups will: * Start the physiotherapy programme at about 2-weeks after surgery. * Receive advice and information about recovery. * Carry out ankle exercises at home, while sitting or lying. * Have at least two physiotherapy appointments between 2 and 6 weeks after surgery. * At week-6, take part in an interview to explore the experiences of the physiotherapy programme and method of interacting with the physiotherapist. * Complete questionnaires about their recovery and their experiences, with a final set at about 12 weeks after surgery. Between 21 to 30 adults who have had surgery for a broken ankle will take part in this study. About twice as many participants will have physiotherapy appointments by video call as those who have appointments at the hospital. The information from this study will help researchers understand whether physiotherapy support by video call are a good fit for people recovering from ankle surgery. It will also help decide whether a larger study should be carried out in the future.

The goal of this clinical trial is to learn if daily supplementation with Low-methoxy (LM) pectin (polysaccharides extracted from citrus peels), which are commonly found in the UK diet (not pharmacological agents), can reduce systemic inflammation and improve gut microbiota composition in adults recently diagnosed with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The main question it aims to answer is: -How does dietary Low-methoxy (LM) pectin supplementation affect systematic inflammation pathways such as those mediated by gut microbiota composition and what are the impacts on general metabolic indicators in individuals with MASLD? Researchers will compare a group taking 15g of LM-pectin with 10g of cocoa powder to a placebo group receiving 10g of placebo with 10g of cocoa powder to see if LM-pectin has measurable effects on inflammation and gut microbiota. Participants will: * Take a daily supplement for 6 weeks: either 15g of LM-pectin with 10g of cocoa powder (intervention), or 10g of placebo with 10g of cocoa powder (control) * Provide stool and fasting blood samples before and after the intervention * Undergo anthropometric measurements (weight, height, waist/hip ratio, and blood pressure) * Complete a case report form (CRF) including demographics and health/medical history * Undergo a FibroScan™ to assess liver health * (Optional) Participate in MRI scans to evaluate gut permeability

In this project, the investigators will develop novel optical coherence tomography (OCT)-Raman spectroscopy and autofluorescence (AF)-Raman spectroscopy systems based on a selective sampling approach optimised for high-resolution analysis of whole lumpectomy specimens and sentinel lymph node (SLN) biopsies, respectively. The aim of using optical coherence tomography is not to detect cancer directly, but rather to identify adipose tissue so that large adipose regions can be excluded from subsequent Raman spectroscopy measurements. Although OCT has limited ability to distinguish tumour tissue from the surrounding normal stroma, adipose tissue exhibits a distinctive appearance in optical coherence tomography images because of its low backscattering properties, resulting from adipocytes that are filled with lipids and contain small, flattened nuclei. In contrast, benign dense tissue (stroma, ducts, and lobules) and malignant tissue produce much stronger backscattering signals. These characteristic patterns enable adipose tissue to be distinguished from other breast tissues using classification models based on optical coherence tomography reflectivity profiles, achieving 94% sensitivity and 93% specificity. Excluding adipose tissue from further analysis reduces the number of Raman spectroscopy measurements required, allowing the remaining, smaller tissue regions to be examined to discriminate between benign and malignant tissue. This flexible and adaptable scanning strategy is expected to improve both diagnostic accuracy and scanning speed, enabling complete assessment of surgical margins within clinically practical timescales. In addition, the investigators will develop a novel (AF)-Raman spectroscopy system based on a selective sampling approach optimised for high-resolution analysis of sentinel lymph node specimens. The purpose of incorporating autofluorescence imaging is to identify the optimal sampling locations for subsequent Raman spectroscopy measurements, thereby improving the efficiency of tissue interrogation while maintaining diagnostic accuracy.

Idiosyncratic drug-induced liver injury (DILI) is an unpredictable adverse hepatic reaction to a medication used in its therapeutic dose. DILI is the second most common cause of itching in adult Hepatology after biliary obstruction. In particular cholestatic or mixed pattern types of DILI (in which bile flow from the liver is impaired) are associated with long-lasting effects as well as reduced quality of life. There is therefore an urgent need to determine the incidence and natural history of itching in DILI and establish a network of centres that will form a basis for a clinical trial to investigate a novel intervention to treat these.

Action Falls is a programme that helps older adults avoid falls and injuries. It finds out why someone might fall and suggests ways to help, like checking their medication and encouraging them to stay active. It was created to try and prevent falls in care homes. It includes training for care home staff, a manual, and a checklist of what to look out for and what to do. Home care providers, local care groups, and older adults who live in the community think Action Falls could be useful too, to help reduce the number of falls in older adults who live at home. The investigators have identified that the programme could be particularly useful for older people who are supported by home care services. The goal of this project is to develop ways to deliver and keep the programme running for older people supported by home care services. A future study will then try it out and see it helps people manage falls in home care. The first part aims to plan and make changes to the current Action Falls programme to make sure it is suitable for use in home care settings. The investigators will do this by * observing what happens on home care visits * asking people who are supported by and who deliver home care how the programme needs to be changed. In a future study the investigators will then deliver the programme across home care in Nottinghamshire and Lincolnshire and evaluate how well it has worked. The study will focus on coastal and rural areas.

The goal of this observational study is to identify progressive changes of quantitative brain and lung imaging, serum and movement-related biomarkers reflecting disease progression in pre-symptomatic infants and very young children (0-5 yo) with a genetic diagnosis of A-T, that could be used in future early-life intervention trials.

To investigate the feasibility of proton pump inhibitor (PPI) withdrawal in inflammatory bowel disease (IBD); the data collected will provide valuable information to inform a future multi-centre randomised controlled trial. Evidence suggests that patients with IBD taking PPIs respond less well to medication and require hospital treatment more frequently than patients not taking PPIs. This may be due to changes in the gut microbiota associated with PPI use. A future definitive trial is planned to investigate clinical outcomes in patients who stop PPIs compared with those who continue PPIs, in order to determine the safety implications of PPI use in IBD. However, several uncertainties remain which require investigation before such a trial can be undertaken. It is currently unknown how many patients with IBD take PPIs, how many can successfully stop taking PPIs, how many would be willing to stop treatment, and how many would remain off treatment long term. In some cases, withdrawal of PPIs may result in a short-term increase in acid reflux symptoms. The willingness of patients to participate in such a study is also unknown. This study will be conducted in GP practices, a setting in which IBD trials have not previously been undertaken. The study will recruit 80 participants with IBD aged 16 years and over who have been taking PPIs regularly for more than six months. Half of participants will be randomised to discontinue PPI therapy. Participants will be followed up for 12 months. The study will provide information regarding recruitment rates within GP practices, optimal methods for PPI withdrawal, and whether stopping PPIs affects IBD outcomes.

The goal of this observational study is to learn about the comparisons of inflammatory markers between IBD and non-IBD (control) participants. The main question it aims to answer is: Are there differences in inflammatory markers between IBD and non-IBD (control) participants.

People who are invited to take part in health research are usually given written information, such as invitation letters, and information sheets. These documents are essential because they help people understand what the study involves and decide whether they want to take part. However, many studies have shown that research information is often too complex, too long, or written in technical language. This can make it difficult for people to fully understand the study and give informed consent. This study aims to assess how clear, accessible, and acceptable draft research documents are for a proposed future doctoral study related to thoracic aortic disease. Thoracic aortic disease is a long-term condition that requires regular monitoring, and people in surveillance programmes may be invited to take part in research. It is therefore important that study information is clear, sensitive, and easy to understand. In this study, staff and students from the University's School of Health Sciences will be asked to review draft recruitment materials. These materials include a study invitation, an information sheet, and interview guide. Participants will be asked to give feedback on how easy the documents are to read, whether the information is clear, whether the tone feels appropriate, and whether the amount of information feels reasonable. The study will also use a standard readability tool to assess whether the documents are written at a level suitable for the public. This research does not involve patients and is considered low risk. Its purpose is to improve research materials before they are used with patients, helping to support informed consent, reduce confusion, and improve ethical and inclusive research practice in future studies.

Individuals living in the UK who are from ethnic minority communities have a higher risk of heart disease and strokes than white individuals. This risk arises from the social determinants of health. These include lifestyle factors such as diet, physical activity and smoking. Improving these lifestyle factors in individuals is an essential part of reducing the chances of heart attacks and stroke. Patients may have diets and lifestyles arising from their cultural and religious backgrounds but receive advice which is not aligned to their own customs and experiences. Receiving advice which is not relevant to their own types of diet and lifestyle customs may create difficulties for patients in managing their heart and circulation health. Moreover, the dissonance between advice given and patient-specific relevance may lead to poorer adherence to the recommendations made to manage their condition. This can lead to poorer health outcomes for these patients. In addition, they may be advised to adopt diets and behaviours which are not appropriate to their cultures and may be also difficult to put into practice. This is important because lifestyle advice aligned to a patient's existing diet, behaviours and cultural beliefs leads to improved control of these health conditions. Learning to provide dietary and lifestyle advice relevant to individual patients needs is an important skill for the clinicians caring for them.

Babies in neonatal intensive care units (NICUs) sometimes need help breathing using a breathing tube (endotracheal tube, or ETT) connected to a breathing machine (ventilator). Over time, bacteria and other substances can build up on the inside of these tubes. This build-up may contribute to infections, inflammation, or breathing problems, but we do not fully understand how often this occurs or what is present within the tubes used in UK NICUs. This surveillance study will collect breathing tubes that have been removed from babies who have been ventilated for more than 12 hours as part of their normal clinical care. No additional procedures or interventions will be performed on babies, and the tubes would otherwise be discarded. Researchers will examine the used tubes and any respiratory secretions (mucus) associated with them. Laboratory testing will identify any bacteria or other microorganisms present and analyse the chemical composition that has accumulated within the tubes and respiratory secretions. By studying these samples, we hope to better understand how breathing tubes become colonised over time and how this may relate to infection and lung health in newborn babies. This study aims to identify the microorganisms that colonises ETT and map them in a contemporary UK neonatal cohort. The information gained from this study may help improve infection surveillance, guide future research, and support the development of strategies to reduce complications associated with mechanical ventilation in vulnerable newborn infants.

Bread remains one of the most widely consumed staple foods worldwide, with wheat flour serving as its traditional foundation. However, the widespread dependence on refined wheat-based bread has paralleled the rising prevalence of type 2 diabetes (T2D), partly owing to its high glycaemic index (GI), which results in rapid increases in blood glucose levels. Enhancing the nutritional quality of bread, therefore, represents an important target for dietary intervention. Developing alternative flour blends for bread production presents a potential strategy for improving glycaemic control and supporting glucose homeostasis. Accordingly, this clinical trial aims to determine whether the partial replacement of wheat flour with legume flours, including chickpea, pea, and lentil, in Arabic bread formulations can lower glycaemic responses compared with traditional Arabic wheat bread.

Undesirable loss of skeletal muscle mass (atrophy) is a common feature of many diseases as well as ageing, bed rest and physical inactivity. Losing muscle can lead to a reduction in one's ability to perform physical activities, and reduce independence and overall health. Muscle mass loss occurs very quickly (i.e., within a few days) after surgery. The investigators previous work has shown that neuromuscular electrical stimulation (NMES) of the thigh muscles on one side of the body can help maintain muscle mass and strength on the stimulated side after surgery. Since then, additional work has been carried out to find the most effective form of stimulation to build muscle. The current study aims to use this refined stimulation protocol in a clinical trial on the wards after major abdominal surgery. The intervention will involve delivering stimulation to both thighs in the few days after surgery, so that the investigators can assess whether this stimulation can preserve muscle mass and strength, and also, patients' ability to perform physical activities after surgery. In addition, the study will aim to find out whether any benefit provided by electrical stimulation can be increased further by taking a protein supplement at the same time.

Background Frozen shoulder (FS) is a common condition and affects how the shoulder moves, making it very stiff and sore. The shoulder joint becomes inflamed and tightened due to scarring in the joint called fibrosis. It can take years to get better, and for around 50% of individuals the symptoms last even longer. FS causes a profound negative impact on physical and mental health, including disturbed sleep, low mood, difficulty performing everyday activities and, in many cases, are unable to continue working. FS affects around 1 in 10 people, and almost twice as many women as men between the ages of 40-60 years, but it is unknown why. It is thought to either be related to changes in sex hormones during the menopause, or due to the way the body handles sugar and fat, which changes with the menopause. However, associations between the menopause transition and FS are not well established and previous evidence has been poor quality. Current treatments include physiotherapy, a steroid injection or surgery but none of these treat the underlying cause of FS. Women with FS said they would like to know why they developed FS and more early treatment options to avoid a long recovery or an operation. Aim This study aims to understand if there is a link between the menopause, changes in blood sugar levels and FS in women. Plan In Part 1, women who have had FS will fill in an electronic questionnaire to give us information about their menopause status at the onset of FS, how long their symptoms lasted, what treatments they tried, and if they had any other health conditions. This will enable us to determine the relationship between the menopause and the onset of FS. In Part 2, the investigators will invite 18 perimenopausal women with recently diagnosed FS and 18 matched women without FS to attend a one-day visit at the University of Nottingham. The investigators will measure their blood sugar levels over two weeks using a small monitor on their arm. The investigators will assess their menopause symptoms and shoulder related outcomes using validated questionnaires. The investigators will assess their shoulder movement and measure body fat and muscle levels, physical activity levels, diet, and take a blood sample to test sex hormones, inflammation and lipids, as well as markers related to frozen shoulder. This will help us to assess the relationship between blood glucose control and the onset of FS in perimenopausal women. Impact This research will help us understand if there's a link between menopause, blood sugar control, and FS. It could lead to new clinical trials testing treatments early in FS, such as a glucose lowering medication or hormone therapy, to help women recover faster and avoid surgery. This may improve clinical outcomes in women with FS and reduce costs associated with treating FS. This important question came directly from patients and has not been studied in depth before. The investigators plan to share the results widely through health newsletters, podcasts, research conferences, and medical journals.

A learning difference or disability is a reduction in intellectual ability (GMC, 2024). It causes lifelong difficulty with everyday activities. Different individuals require different levels of support. Individuals with learning disability may also have learning difficulties and mental health problems, but these conditions do not always co-exist. Learning difficulties affect the way someone processes information. They are not related to intelligence but can affect learning and education. People with learning differences can experience higher rates of mental and physical ill-health. The individual's life expectancy is shorter than the average for the population. This is related to access and experience of health care. These patients may experience discrimination affecting their healthcare. Discrimination arises from staff and organisational attitudes towards patients and judgements about their quality of life. These individuals' care is also at risk of diagnostic overshadowing where a patient's symptoms are attributed to their disability rather than a disease. Many people with learning disabilities may find it harder to use healthcare services, and the investigators want to find out what challenges these individuals face. For example, do these patient have trouble understanding what is being said to them? Are there issues with getting an appointment or understanding the information about their health? This project focuses on understanding the experiences of people with learning disabilities when they use health services. How easily do can these individuals communicate with their clinician? Are there barriers in accessing care? Do these individuals feel respected and listened to during their appointments? How should healthcare staff be trained to provide better care to these patients? The investigators will be speaking directly to patients with learning disabilities living in Derbyshire. This will be by interviews encouraging the patients to share their thoughts and experiences. The information the investigators gather will help understand these people's experiences of healthcare and how this could be improved. The investigators will also undertake an anonymised survey of medical students on their perceived learning needs regarding individuals with learning differences. This information will be used to develop educational resources for clinical teachers. medical students and staff. Working with the volunteers will better prepare future doctors to provide holistic care for patients with learning differences.

The goal of this observational study is to investigate if diathermy (a surgical tool that uses electrical energy to control bleeding) has any affect on the accuracy and functioning of continuous glucose monitoring systems in adults and young people with Type 1 Diabetes. The main questions this study aims to answer is - \- Does the accuracy of continuous glucose monitoring systems change after use of diathermy? Participants will: * Have their height and weight checked. * Provide information about their medical history including type of diabetes, other medical conditions and any current medications they take. * Have paired glucose meter and sensor glucose measurements taken every 15-75 minutes from up to 4 hours before surgery until up to 4 hours after the end of surgery. * Have two blood samples taken to measure glucose levels, The first one will be before the use of diathermy and the second will be after the use of diathermy.

X-linked hypophosphataemia (XLH) is a rare, hereditary condition. The genetic defect leads to low blood phosphate levels and vitamin D suppression. Phosphate is required for strong bones and teeth and to store energy in cells. Low phosphate leads to soft bones (rickets). Patients experience bowed legs, short stature, bone pain and dental pain. Prior to Burosumab, conventional treatment of XLH previously consisted of two medications. On this regimen, patients take oral phosphate supplements 4-6 times a day and an active form of vitamin D daily. This treatment can leave patients with residual symptoms. They report significant disabilities and reduced quality of life. Burosumab (Crysvita, Kyowa Kirin) is now the standard paediatric treatment for XLH. It is given once a fortnight by injection under the skin. Early studies used a starting dose of 0.4mg/kg per dose. NICE recommends a starting dose of 0.4mg/kg, a normal maintenance dose of 0.8mg/kg and a maximum of 2mg/kg (up to 90mg). The British National Formulary for Children (BNFC) gives the same advice. However, the European Medicines Agency recommends a starting dose of 0.8mg/kg per dose which is, therefore, the standard starting dose now. Some patients achieve symptom and biochemical control on less than 0.8 mg/kg per dose. They may be exposed to higher doses than necessary. To date, approximately 200 patients have started on Burosumab in England. They are all managed by specialist centres. The rare status of XLH means there are relatively few patients in each centre. Treatment effects and trends can only be described by collating data from multiple centres. The investigators will undertake a review across multiple English centres of the doses of Burosumab. The review will only collect data already in the patients' health records. It will look at factors affecting the starting dose. The investigators will assess the association between dose, blood markers and growth.

The goal of this clinical trial is to improve patient care after acute kidney injury (AKI). It has three related parts. The main questions it aims to answer are: 1. Is creatinine or cystatin a more reliable assessment of kidney function after AKI? 2. What are the experiences of patients after AKI? 3. What interventions should be recommended to improve assessment and support of patients after AKI? Participants will be asked to do one or more of: * blood tests to measure kidney function in different ways * have measurement of their body composition * complete questionnaires about their symptoms * have an interview with a researcher about their experiences * discussion to develop an action plan based on findings

Caloric restriction programmes are highly effective and safe interventions for inducing rapid weight loss and improvements in glycaemic control. The landmark DiRECT study showed that 68% of people completing a caloric restriction intervention achieved remission of type 2 diabetes (T2D) by one year. Consequently, the NHS Path to Remission (PTR) programme was developed to stimulate diabetes remission in individuals that meet certain criteria. Unfortunately, long-term follow-up of the DiRECT study suggests that in the majority of participants that achieved remission, diabetes relapses within 5 years. This necessitates a focus on identifying methods to improve long-term maintenance of diabetes remission. High-intensity interval training (HIIT) involves several brief bursts of intense exercise, interspersed with recovery breaks, and is becoming increasingly popular. HIIT can cause improvements in cardiovascular fitness, reduce blood pressure, and lower body fat content in only a fraction of the time of traditional exercise methods. Specific to T2D, HIIT has been shown to improve pancreatic beta cell function, which is critically important for maintenance of long-term diabetes remission. This pilot study is being conducted to determine whether participating in a home-based HIIT training programme may help maintain beta cell function in individuals that have achieved diabetes remission following the NHS PTR programme. The study will take place at the Royal Derby Hospital. The intention is to recruit 20 participants from Derbyshire or Nottinghamshire that have achieved diabetes remission in the NHS PTR programme. Participants will be recruited following discharge from the programme and allocated to either perform a HIIT training programme (intervention group), or continue with usual care (control group) for 16 weeks. Before starting, participants will attend the research department to have initial measurements taken including bioimpedance, fasting bloods, an intravenous glucose tolerance test, muscle ultrasound, electromyography and cardiopulmonary exercise testing. Following this, those in the intervention group will be asked to perform a home-based HIIT training programme 3 times per week and record details of each session in a booklet. The control group will be asked to continue with their habitual levels of physical activity. Participants will be contacted regularly to ensure their safety and compliance.

This study aims to look at how sleep disturbance affects people who have had a traumatic brain injury. Sleep disturbance can include waking frequently in the night, difficulty falling asleep, excessive sleepiness or changes to usual sleep patterns. Investigators define traumatic brain injury as an injury caused by a forceful bump, blow, or jolt to the head or body, or from an object entering the brain. This results in a disturbance of normal brain function, that can be temporary. By understanding the relationship between sleep disturbance and traumatic brain injury, investigators will hopefully improve care and treatment for people with a traumatic brain injury. Investigators are looking to understand each participant's experience of sleep disturbance, as well as measuring sleep, using a device that monitors movement and sleep quality. Investigators are interested how sleep disturbance impacts things like day-to-day life and activities, such as work or leisure. Investigators are also interested in mental health, such as depression or anxiety.

Linaclotide is a medicine used to treat constipation and irritable bowel syndrome with constipation (IBS-C). It works by acting on the surface of the gut lining, where it increases the movement of salt and water into the bowel. This softens stools, makes them easier to pass, and can also reduce gut pain One advantage of linaclotide is that, unlike some natural substances in the gut, it is stable and can act throughout the intestine. Studies in animals show that it has the strongest effect in the upper small intestine, but it may act in other parts of the bowel as well. In people, however, it is not yet clear whether linaclotide mainly works in the small intestine or in the large intestine (colon). Knowing this is important, because it could help the investigators understand whether linaclotide might also be useful in other conditions, such as cystic fibrosis, where the gut does not handle fluid properly. Linaclotide is taken as a capsule, but less than 1% is absorbed into the bloodstream. Instead, it stays in the gut, where it is broken down into smaller active parts. This means both the small intestine and colon may be exposed to its effects. Until now, it has been hard to study this because traditional methods only measure one part of the gut at a time. A team at the University of Nottingham has developed MRI scanning methods that can safely and non-invasively measure water content in the small intestine and colon. The aim of this pilot study is to use MRI in healthy volunteers to see exactly where linaclotide acts. This knowledge will help optimise future studies in conditions such as cystic fibrosis.