Clinical Research Directory

VITAL-IMPACT: Improving Cardiometabolic Health in Black Individuals Through Therapeutic Augmentation of Cyclic Guanosine Mono-Phosphate Signaling Pathway

This study investigates the potential of vericiguat, a soluble guanylate cyclase stimulator, to improve cardiometabolic health in obese Black individuals with insulin resistance by directly enhancing cyclic guanosine monophosphate (cGMP) activity. Given that this population has been shown to have lower cGMP activity and the association of lower cGMP activity with increased cardiometabolic disease risk, the proposed study hypothesizes that augmenting cGMP activity in obese individuals will improve insulin sensitivity and energy expenditure. This study is a placebo-controlled randomized trial involving 200 Black obese participants with insulin resistance, assessing the effects of vericiguat on insulin sensitivity, resting, and exercise-induced energy expenditure over 12 weeks. Additionally, it will explore changes in brown adipose tissue and gene expression related to energy metabolism in white adipose tissue, aiming to provide insights into how increasing cGMP activity may improve cardiometabolic health in Black obese individuals.

Study of Clinical Response to Acute Metformin By Leveraging Evaluations During a Mixed Meal Tolerance Test for Exploring Glycemia and GeneticS

The purpose of this research study is to examine whether specific genes (e.g. SLC16A11) affect how human beings respond to food and a medication that is commonly used to treat type 2 diabetes. The food the investigators will be studying is specially prepared to contain protein, carbohydrate, and fat. The drug the investigators are studying is metformin. The investigators hypothesize that physiological responses to the meal and to the medication will differ between carriers and non-carriers of genes associated with type 2 diabetes.

Tracing Of Real-time glu13Cose Metabolism in Human Immune Cells

The purpose of this study is to understand how cells of the immune system use the common sugar glucose to fuel energy production and as a building block within the cell. Investigators will intravenously infuse a non-radioactive glucose tracer into participants over a few hours and collect immune cells from the blood to track uptake and usage of this glucose within these immune cells.

VITAL: Vaccination, Immunity, Time-restricted Eating, Aging and Lifestyle

The aim of this study is to investigate the effects of a four-week time-restricted eating (TRE) intervention on autophagy, immune function, and vaccine response to a seasonal influenza and COVID-19 vaccines in older healthy subjects.

GLYLO Supplement Pilot Trial on Glycation and Aging in Postmenopausal Women

The aim of this study is to assess the effectiveness of GLYLO, a dietary supplement, in postmenopausal women aged 45 to 65 who are overweight or obese and have elevated HbA1c levels. Specifically, the study seeks to evaluate whether GLYLO can reduce advanced glycation end products (AGEs) levels, which are harmful compounds formed when sugar attaches to proteins or fats in the body and can contribute to aging and disease. The primary outcome of the study is to determine if GLYLO reduces AGEs, enhances metabolic and hormonal health, and mitigates age-related functional decline. This study includes one screening visit and three testing visits over a 6-month period. After eligibility is confirmed, participants will be randomly assigned to one of two groups to take either GLYLO (two capsules daily) or a placebo at home for 24 weeks. Participants will provide blood samples at every visit. During the three testing visits, they will complete physical performance and cognitive function tests, provide both blood and urine samples, and fill out quality of life and 24-hour dietary intake questionnaires. The dietary intake questionnaires will be completed only twice i.e. at the baseline visit and again at the final 6-month visit.

Caloric Balance Markers Study

The purpose of CaBooM is to identify and characterize biomarkers of caloric balance-the relationship between energy intake (calories consumed) and energy expenditure (calories burned).

Studying Phenotypic Risks for Obesity and Underlying Traits in Young Infants

The purpose of this research study is to understand how infants metabolize different meals and to develop clinical tools which identify infants as having two different phenotypes. The phenotypes are the 1) metabolic "thriftiness" and 2) the metabolic flexibility.

Effects of Casein Protein on Metabolism When Taken Prior to Sleep and in the Morning

The purpose of this study is to investigate the effect of casein protein consumption both prior to sleep as well first thing in the morning on metabolism (increase satiety and appetite, lower resting metabolic rate, and lower blood sugar levels), when compared to nighttime protein or placebo consumption alone. Protein itself is a macronutrient that not only helps the body repair itself, and play a critical role in growth, it also aids in increasing satiety and decreasing appetite. Casein protein specifically is slow digesting dairy protein which may impact the body's metabolism for a longer period than other dairy proteins such as whey. The literature demonstrates nighttime protein ingestion prior to sleep increases metabolic rate and satiety the next morning. However, there appears to be no data on the metabolic effects of protein ingested both at night and in the morning.

The Impact of Nicotinamide Mononucleotide Sustained-release Tablets on Immunosenescence and Metablism in Middle-aged and Elderly Individuals With Metabolic Disorders.

The ageing of our country is increasing and the ageing of the population has led to a significant increase in aging related diseases. During the aging process of the organism, cellular senescence can occur in all systems of the body, of which the senescence of the immune system is called immunosenescence. Some studies have shown that metabolic disorders can also trigger aging. This study investigated the effect of nicotinamide mononucleotide (NMN) supplementation on immunosenescence in middle-aged and elderly people through a placebo-controlled long-range clinical trail, aiming to provide a new method to improve immunosenescence. The effects of NMN supplementation on glucose and lipid metabolic indexes, body composition and telomere length of peripheral blood cells are also investigated, which may open up new ideas for the prevention and treatment of glucose and lipid metabolic diseases.

NAUTICAL: Effect of Natriuretic Peptide Augmentation on Cardiometabolic Health in Black Individuals

Black individuals are more likely to have decreased insulin sensitivity which results in a high risk for the development of cardiometabolic disease. The reasons for this are incompletely understood. Natriuretic peptides (NPs) are hormones produced by the heart that play a role in regulating the metabolic health of an individual. Low circulating level of NPs is an important contributor to increased risk for diabetes. The NP levels are relatively lower among Black individuals thus affecting their metabolic health and putting them at a higher risk for diabetes. This study aims to test the hypothesis that by augmenting NP levels using sacubitril/valsartan, among Black Individuals one can improve their metabolic health (as measured by insulin sensitivity \& energy expenditure) and help establish the role of NPs in the underlying mechanism behind increased risk for cardiometabolic disease in these population.

Personalized Responses to Dietary Composition Trial 3

The PREDICT 3 study will build on previous research in over 2,000 individuals to further refine machine learning models that predict individual responses to foods, with the aim of advancing precision nutrition science and individualized dietary advice. The study incorporates both standardized and controlled dietary intervention, for the purpose of testing postprandial responses to specific mixed meals, in addition to a free-living period with a dietary record for measuring responses to a large variety of meals consumed in a realistic context, where the role of external factors (e.g. exercise, sleep, time of day) on postprandial responses may be determined. For the first time this PREDICT study is built on top of a commercial product which will allow access to a much larger group of participants who are already collecting large amounts of data through digital and biochemical devices that can contribute to science.

Evaluation of Blood and Cardiac Protein O-GlcNAcylation Levels in Cardiac Surgery in Children

Cardiac surgery requires the use of extracorporeal circulation (ECC). Age-related differences in inflammatory response, the greater susceptibility of immature organ systems to injury and the larger ratio of extracorporeal circuitry to patient size make younger and smaller patients more vulnerable to organ injury. The main problem associated with ECC in neonates and infants is the duration of ECC due to heavier surgeries leading to a prolonged inflammatory state resulting in capillary leak syndrome, low cardiac output syndrome and organ dysfunction, resulting in higher morbidity and mortality. The means of limiting this inflammatory response remain limited. Future studies should aim to address new post-ECC prophylactic targets to improve myocardial and endothelial function. Cardiac metabolism is an important area of research because it plays a central role in maintaining cardiac function under stress. The study of O-GlcNAcylation could therefore be an interesting therapeutic target, given the beneficial role of its stimulation in acute stress situations, as demonstrated in sepsis.

Treatment of Sleep Apnea to Improve Metabolic Health

Diabetes and prediabetes prevail among obstructive sleep apnea (OSA) patients. OSA and short sleep both detrimentally affect glycemic control regardless of obesity. With 1 in 10 adults having diabetes, 1 in 10 with prediabetes, and an estimated 600,000 affected by OSA in Sweden, attaining glycemic control is crucial. Though continuous positive airway pressure (CPAP) is the most effective treatment for OSA, its application lacks personalization, ignoring factors like comorbidities and sleep duration. Key unanswered questions regarding CPAP's impact on glycemic control include: 1) Does high CPAP adherence optimize glycemic control? 2) Should short sleep be addressed alongside OSA treatment for glycemic control? 3) Does long-term diabetes hinder CPAP's glycemic control efficacy? The purpose of this project is to enable precision health in CPAP treatment and producing a personalized treatment model for achieving glycemic control in patients with OSA, treated with CPAP. Taking advantage of a large unique patient cohort (600 patients followed over 18 months) with extensive and objective measures on CPAP adherence, OSA reduction, sleep duration, as well as information on comorbidities, anthropometric, lifestyle data, and a wide range of biomarkers related to glycemic control. This comprehensive approach and in-depth analysis will address these questions and generate a personalized treatment strategy for glycemic control in CPAP-treated OSA patients.

Ketone Esters and Metabolism During Recovery from Endurance Exercise

Infusion of beta-hydroxybutyrate can suppress endogenous glucose production, which may result in increased net liver glycogen storage. If ketone esters exert similar effects, then the increase in liver glycogen storage may have implication for recovery from exercise and subsequent exercise performance. The aim of this study is to assess the effects of ketone esters ingested during recovery from exercise, on metabolism and subsequent exercise capacity.

Identifying Wearable Biomarkers to Monitor Dietary Intake

Background: Measuring what people eat is a challenge in nutrition research. Traditional methods, like food diaries, rely on self-reporting of individuals, and suffer from poor accuracy and recall bias. Aims: This project aims to identify physiological biomarkers related to food and energy intake, which may be used to develop an objective tool to estimate individuals' food intake in future. Eating behaviours are accompanied by significant physiological changes such as skin temperature, blood oxygen saturation, pulse rate etc. The investigators intend to investigate whether monitoring these physiological changes can help us estimate eating behaviour, such as meal size, eating speed, and duration of meals. Study design: Ten healthy adults will be invited for two study visits at NIHR Imperial Clinical Research Facility. Each visit will last for approximately 2 hr. They will consume a high- and low-calorie meal designed by nutritional researchers in a randomised order. During eating events, the investigators will track their physiological changes via a bedside monitor and wearable sensors. Blood samples will be taken from participants to measure their glycaemic response. Associations between energy load, glycaemic response, and physiological changes will be investigated. Our findings may promote an accelerated development of a wearable tool for dietary assessment in future.

Nutrition and Inflammation in Patients With Head and Neck Cancer

An estimated 1500 people in Sweden will annually be diagnosed with head and neck cancer (HNC). Five year survival is approximately 69%. Long-term sequelae are common and in particular nutritional problems and fatigue. Radiotherapy (RT) is the cornerstone of treatment, either as single modality treatment or combined modality treatment. RT can induce immune responses at the site of tumor. It has been demonstrated that RT can lead to a strong systemic immune response . We have previously shown that an increase of conventional measures of systemic immune response to RT varied significantly across individuals. We predict that local immune response plays a major role in the antitumor effect. We also predict that a strong systemic immune response contributes to malnutrition and influence on survival. And malnutrition may lead to a worse response to RT. The overall aim of this multicenter observational longitudinal study is to prospectively identify immunological and metabolic variables that affect the outcome of HNC patients. We will systematically investigate the local and systemic immune response induced by RT as well as explore alterations in metabolite composition induced by disease and treatment through global metabolite profiling. A platform for studies on immuno-metabolic changes in HNC patients has been established in the Uppsala-Orebro and Northern regions. Approximately 370 patients per year are eligible. Findings in this study can have implications on the development of personalized therapy in patients with HNC. The long-term benefit of the study will be the identification of measures for improved patient surveillance in order to improve the general and nutritional outcomes.

The Effects of Night Shift Work on Health Across the Menstrual Cycle

The study aims to investigate the effects of sleep deprivation on women's health across different phases of the menstrual cycle.

ImpACt of Very High Protein Content Enteral nUtrition Formulas on Critically Ill MUltipLe trAuma paTiEnts

This prospective observational randomized study aims to determine energy, protein intake and gastrointestinal tolerance while using enteral nutrition formulas with very high protein content and enteral nutrition formulas with normal protein content. * Differences regarding achieving protein and calorie daily targets when using enteral nutrition formulas with different protein content * Differences regarding residual gastric volume when using enteral nutrition formulas with different protein content * Differences regarding body composition when using enteral nutrition formulas with different protein content

RMR Monitoring Feasibility and Acceptability

Obesity is a leading risk factor for chronic diseases such as type 2 diabetes, cancer, and cardiovascular disease. Generic weight management programs that target dietary intake and physical activity have been shown to be ineffective in maintaining weight loss beyond a 6-month period. Personalizing weight management programs produces more weight loss than generic programs, possibly through improved self-efficacy (confidence in one's ability to control weight through behavior). One way to personalize diet goals for individuals is by resting metabolic rate (RMR; 'metabolism'). This study will explore adherence and satisfaction of 6-weeks repeated at-home measures of metabolism using a portable device in healthy adults with and without obesity. Relationships among adherence and satisfaction outcomes to health behavior variables will be explored using dietary recalls, exercise monitors and questionnaires. Investigators will conduct a 6-week, one-arm feasibility study in order to address these questions. Twenty men and women ages 19-65 will be recruited (up to n=25 participants), among which 10 participants will have a body mass index (BMI) of ≥30kg/m2 (classified as having obesity), and the remaining 10 participants will have a body mass index (BMI) of \< 29.9kg/m2 (classified as not having obesity). The baseline study visit will evaluate participant's anthropometric measures, RMR using the ParvoMedics TrueOne 2400 and Breezing indirect calorimeters, psychological and behavioural related parameters. An activPAL device will be provided to measure participant physical activity. Completion of a 3-day diet record following the baseline study visit, in which participants keep a record of all food and beverages consumed over 2 weekdays and 1 weekend, is required. Participants will be asked to use the Breezing device from home to measure their RMR one time/week on the same day of the week (± one day) and at the same time each morning for six consecutive weeks following the baseline visit. A weekly Qualtrics survey will be sent to participants to monitor adherence. A follow-up visit after the six weeks will assess participant's body composition using a Dual X-ray Absorptiometry (DEXA), in addition to completion of a user satisfaction interview with a study team member for descriptive analysis. The measures taken at the baseline study visit will be repeated at the follow-up visit.

Assessment Metabolic Flexibility in Middle-aged Individuals: The Nutritional Impact of Cheese Consumption

The aim of the study will be to evaluate the impact of consumption of meat and dairy products from extensive or intensive farming on apparently healthy individuals aged between 45 and 65 years, a stage of life associated with reduced metabolic flexibility and changes in lipid metabolism. The study will analyze: 1. The transcription factor PPAR-α determined by the gene expression of PPAR-α in white blood cells, variations in circulating fatty acid metabolism, and the endocannabinoid system determined by circulating analysis of N-acylethanolamine (NAE), and 2-monoacylglycerols (2-MG); 2. Metabolic flexibility, determined by indirect calorimetry in fasting condition during an incremental exercise; 3. Body composition, determined by bioimpedance analysis, waist circumference, and waist-to-hip ratio.

HIIT vs MICT During Pregnancy and Health and Birth Outcomes in Mothers and Children

Regular exercise during pregnancy and postpartum leads to health benefits for mother and child. Inactivity during pregnancy and after delivery is now treated as risky behavior. Physically active pregnant women significantly less often suffer from, among others, gestational diabetes, excessive weight gain, lipids disorders, hypertension, preeclampsia, depressive symptoms, functional and structural disorders, including stress urinary incontinence, back pain or diastasis recti abdominis (DRA). Prenatal physical activity reduces the risk of premature delivery and miscarriage, fetal macrosomia, complications in labor or the risk of metabolic disorders in children. High-intensity interval training (HIIT) has become one of the most popular trends in the fitness sector. The effectiveness of HIIT on a number of health indicators has been proven in various populations but limited data are available on HIIT during pregnancy. The first hypothesis is that the HIIT, implemented during pregnancy and after childbirth, as a stronger exercise stimulus, will have a better impact on selected biological and psychological parameters of mothers, as well as on selected health parameters of their children, compared to the MICT (moderate intensity continuous training). Therefore, it promises better preventive effects on pregnancy complications and ailments as well as non-communicable diseases occurring in these populations. In the second hypothesis, it was assumed that HIIT and MICT implemented during pregnancy and after childbirth, tailored to the specific needs of the perinatal period, will not differ in the effectiveness of maintaining normal functional parameters in women, including prevention of urinary incontinence, back pain, DRA, etc. Pregnant women who apply for the study will be divided into three groups: those attending the HIIT, MICT or educational programs. During the study, the participants will be under standard obstetric care. As comparative groups, non-pregnant women will be also recruited. The investigators will collect data on selected biological, functional and psychological parameters in the study women at each trimester of pregnancy, during the puerperium and one year after childbirth. The data from the medical documentation on the course of childbirth and the assessment of the new-born, as well as the results of preventive examinations in the study women's children aged one, two, four and six years will be also analyzed.

Cancer-associated Muscle Mass - Molecular Factors and Exercise Mechanisms

Muscle mass loss is a common adverse effect of cancer. Muscle mass loss occurs with or without reduction in body weight. Cancer cachexia (CC) is the involuntary loss of body weight of \>5% within 6 months and it occurs in 50-80% of patients with metastatic cancer. It is estimated that CC is a direct cause of up to 30% of all cancer-related deaths. No treatment currently is available to prevent CC, likely because the chemical reactions that causes of this devastating phenomenon in unknown. No treatment currently is available to prevent muscle mass loss in patients with cancer but is urgently needed as the reduced muscle mass and function is associated with impaired physical function, reduced tolerance to anticancer therapy, poor quality of life (QoL), and reduced survival. There is evidence of an interdependence between informal caregiver (e.g. spouse) and patient QoL. Thus, identifying caregiver distress and needs can potentially benefit QoL for patients with cancer cachexia. Despite the enormous impact on disease outcomes, it is not known why the loss of muscle mass and function occurs and very few studies have investigated the underlying molecular causes in humans. In particular, there is a severe lack of studies that have obtained human skeletal muscle and adipose tissue sample material. Such reference sample materials will be invaluable to obtaining in-depth molecular information about the underlying molecular causes of the involuntary but common muscle mass and fat mass loss in cancer. At a whole body level, cancer cachexia is associated with reduced sensitivity to the hormone insulin, high levels of lipids in the blood, and inflammation. Within the skeletal muscle, the muscle mass loss is associated with elevated protein breakdown and reduced protein build-up while emerging, yet, limited data also suggest malfunction of the power plants of the cells called mitochondrions. The role of malnutrition and how it contributes to weight loss is understood only to the extent of the observed loss of appetite and the reduced food intake because of pain, nausea, candidiasis of the mouth, and breathlessness. Evidence is increasing that the environment of the intestinal system could be implicated in cancer cachexia, yet, the possible effect of cancer and the cancer treatment on the intestinal environment is not understood. Thus, large and as yet poorly understood details of this syndrome precede a later weight loss. Exercise training could help restore muscle function and how the chemical reactions works in cancer. In healthy people, and patients with diabetes, cardiovascular disease, and obesity exercise potently improves health. Exercise has been thought to slow down the unwanted effects of cancer cachexia by changing the reactions mentioned above. Thus, there is a tremendous gap in our knowledge of how and if exercise can restore the cells power plants function, muscle mass, strength, and hormone sensitivity in human cachexic skeletal muscle. Tackling that problem and examining potential mechanisms, will enable us to harness the benefits of exercise for optimizing the treatment of patients with cancer. The data will provide novel clinical knowledge on cachexia in cancer and therefore addressing a fundamental societal problem. Three specific aims will be addressed in corresponding work packages (WPs): * investigate the involvement of hormone sensitivity of insulin and measure the chemical reactions between the cells in patients with lung cancer (NSCLC) and describe the physical performance and measure amount of e.g. muscles and adipose tissue across the 1st type of cancer treatment and understand how that is related to the disease and how patients and informal caregiver feel (WP1). * find changes in the chemical reactions in skeletal muscle, adipose tissue (AT), and blood samples in these patients, to understand how to predict how the disease will develop (WP2). * measure changes of skeletal muscle tissue in response to exercise and see if it might reverse the hormone insensitivity and improve muscle signaling and function (WP3). The investigators believe that: * the majority of patients with advanced lung cancer, at the time of diagnosis already are in a cachectic state, where they lose appetite, and have hormonal changes, and an overall altered chemical actions between the cells affecting both muscle mass and AT. The investigators propose that all this can predict how the disease will progress, and how patient- and informal caregiver fell and how they rate their quality of life. * lung cancer and the treatment thereof is linked with changes in the blood, the muscle tissues, and the adipose tissues, especially in patients experiencing cachexia, that could be targeted to develop new treatment. * exercise can restore the muscles and improve insulin sensitivity and improve the function of the cells power plants in patients with lung cancer-associated muscle problems.