Clinical trials

Although type 1 diabetes (T1D) has traditionally been considered a disease associated with a lean phenotype, it is estimated that up to 2 out of 3 people living with T1D are overweight or obese, factors linked to an increased risk of complications in these patients. The available evidence regarding nutritional strategies for weight loss in T1D is very limited, and clinical trials are needed to determine how to effectively and safely promote weight loss in this population. In recent years, low-carbohydrate diets and several intermittent fasting protocols have demonstrated efficacy in promoting weight loss both in patients with type 2 diabetes and in patients with obesity without diabetes. In this study, we will evaluate the efficacy of moderate carbohydrate restriction, time-restricted eating, and standard calorie restriction for weight loss in adults with T1D and overweight/obesity.

SucroMet is designed to evaluate how adding two commonly used sweeteners-sucrose (table sugar) and sucralose (a low-calorie sweetener)-at low and high doses may influence glucose regulation, including insulin resistance and fasting plasma glucose, in adults aged 18 to 65 years with normal weight, overweight, or obesity. The low-dose intervention consists of 5% of the Estimated Energy Requirement (EER) from sucrose or 5 sucralose tablets per day (approximately 33.35 mg/day of sucralose). The high-dose intervention consists of 10% of EER from sucrose or 10 sucralose tablets per day (approximately 66.7 mg/day of sucralose). These doses maintain the planned 1:2 exposure ratio between the low- and high-dose intervention groups. Before the intervention begins, participants' habitual dietary intake is assessed and, when necessary, minor dietary adjustments are made to support a stable overall eating pattern while maintaining energy intake. Participants then complete a four-week run-in period during which these recommendations are followed, and dietary records are used to verify dietary stability before the intervention starts. Participants will consume the assigned sweetener incorporated into foods or beverages that they already consume as part of their habitual diet, without substantial changes to their usual eating patterns. The intervention includes two consecutive 12-week phases, one involving solid food intake and the other involving liquid intake, separated by a two-week washout period. This design allows evaluation of the effects of sweetener type, dose, and mode of consumption. The primary outcomes are changes in glucose regulation, including fasting plasma glucose and insulin resistance assessed by HOMA-IR. Secondary outcomes include changes in body composition, anthropometric measurements, blood pressure, routine biochemical parameters, gut microbiota composition, DNA methylation patterns in peripheral blood cells, and biomarkers related to inflammation, oxidative stress, and metabolomic profiles measured in blood and urine. Participants will attend scheduled study visits for anthropometric assessments, dietary evaluations, and biological sample collection. Blood, urine, and stool samples will be obtained at baseline and after each intervention phase. The study aims to address the following questions: 1. Do metabolic responses to sucrose and sucralose, including changes in insulin resistance (HOMA-IR) and fasting plasma glucose, differ according to participants' body mass index (BMI)? 2. Do low and high doses of sucrose and sucralose differentially affect glucose regulation, body composition, and metabolic health? 3. Does the mode of intake (solid versus liquid) influence changes in gut microbiota composition? 4. Are changes in DNA methylation patterns in peripheral blood cells associated with the consumption of sucrose and sucralose at different doses and in different forms? 5. Do different doses of sucrose and sucralose influence biomarkers related to inflammation, oxidative stress, and metabolomic profiles?

This study investigates how the immune system of children with celiac disease responds to controlled, small amounts of gluten. Children on a strict gluten-free diet are randomly assigned to receive either placebo, 50 mg of gluten, or 5 g of gluten once daily for three days, simulating real-life accidental exposure or dietary transgression. Blood samples are collected on Day 1 (before gluten intake) and Day 8 (five days after the last dose). Stool and urine samples are also collected for complementary analyses. Using single-cell ribonucleic acid (RNA) sequencing, T-cell receptor sequencing, microRNA profiling, and exploratory metabolomics, the study aims to characterize changes in immune cell populations and gene expression after gluten exposure. The objective is to determine whether even very small amounts of gluten induce measurable systemic immune responses and whether these responses differ according to the dose administered. Understanding these mechanisms may support the development of new biomarkers and improve clinical management of pediatric celiac disease.

Medical Nutritional Therapy (MNT) is critical for patients with impaired oral intake and is typically administered via enteral nutrition (EN). Current infusion practices-continuous 24-hour enteral nutrition for hospitalised patients-may induce circadian misalignment (chronodisruption). This misalignment can negatively impact metabolic function, sleep quality, and overall quality of life for both patients and caregivers. Synchronising MNT administration with circadian rhythms may improve metabolic balance, sleep, and patient well-being. Hypothesis: The timing of the administration of Medical Nutritional Therapy via continuous enteral nutrition (EN) in hospitalised patients may induce chronodisruption in biological rhythms (clock genes). This disruption can affect the metabolism of carbohydrates, lipids, and proteins, contributing to morbidity and altering chronotype, quality of life, and sleep patterns.

Medical Nutritional Therapy (MNT) is critical for patients with impaired oral intake and is typically administered via parenteral nutrition (PN). Current infusion practices-nocturnal home parenteral nutrition (NHPN)-may induce circadian misalignment (chronodisruption). This misalignment can negatively impact metabolic function, sleep quality, and overall quality of life for both patients and caregivers. Synchronising MNT administration with circadian rhythms may improve metabolic balance, sleep, and patient well-being. Hypothesis: The timing of the administration of Medical Nutritional Therapy via nocturnal home parenteral nutrition (NHPN) in outpatients may induce chronodisruption in biological rhythms (clock genes). This disruption can affect the metabolism of carbohydrates, lipids, and proteins, contributing to morbidity and altering chronotype, quality of life, and sleep patterns.

The goal of this study is to evaluate the effects of nutritional supplementation and physical activity interventions on recovery, muscle strength, nutritional status, inflammation, and metabolic health in adults with colon cancer undergoing surgery. Patients with colon cancer frequently experience loss of muscle mass, reduced physical function, and nutritional deterioration both before and after surgery, which may adversely affect recovery and quality of life. A key objective of this study is to assess whether a postoperative intervention combining nutritional supplementation with beta-hydroxy beta-methylbutyrate (HMB) and vitamin D, together with a structured physical activity program, can improve muscle strength and functional recovery following colon cancer surgery. This study aims to answer the following questions: * Does nutritional supplementation with HMB and vitamin D, combined with postoperative physical activity, improve muscle strength and physical function following colon cancer surgery? * How do nutritional and lifestyle interventions influence nutritional status, gut microbiota composition, and biological markers of inflammation and metabolism during the recovery period? * Are there differences in recovery outcomes between patients receiving different types of nutritional support, with or without supervised physical activity? Participants will be adults diagnosed with colon cancer who undergo surgical treatment at the Hospital Universitario Virgen de la Victoria in Málaga, Spain. Patients will be recruited prior to surgery and will enter a prehabilitation phase integrated into routine care provided by the Endocrinology and Nutrition Department. During this prehabilitation phase, nutritional status will be assessed and optimized using standard clinical care, including oral nutritional supplementation when indicated. The aim is to improve the patient's condition before surgery. Approximately one month after surgery, once initial postoperative recovery has been completed, participants will enter the intervention and assessment phase (baseline visit). Participants will then be randomly assigned to one of four study groups in a 2×2 factorial design. These groups combine two nutritional strategies (standard care or supplementation with HMB and vitamin D) and two physical activity approaches (supervised exercise or general activity recommendations). The physical activity component, supervised by the Endocrinology and Nutrition team, will be objectively evaluated using an accelerometer-based device. Participants will be followed for approximately six months, with assessments at about 3 and 6 months after the baseline visit. At each visit, participants will undergo: * Body composition measurements * Muscle strength and physical performance tests * Collection of blood, urine, and stool samples * Questionnaires on health status and quality of life The results of this study will contribute to a more profound understanding of how tailored nutritional strategies and postoperative physical activity may support recovery and functional health in patients undergoing surgery for colon cancer.

This randomized clinical trial aims to evaluate the effects of mentalization-based group psychotherapy in patients diagnosed with anxiety and/or depression disorders. In total 100 users of mental health communitary services will be recruited for this study. Participants will be randomized in two parallel groups: to receive usual acceptance and commitment therapy group intervention (control group) or to receive brief mentalization-based group psychotherapy (intervention group). Participants in the trial will be assessed at baseline and at 3 months.

Obesity is a chronic disease with high relapse rates after initial weight loss. Thyroid hormones modulate energy expenditure, body composition, and thermogenesis; higher TSH within the reference range and subclinical hypothyroidism have been associated with adverse metabolic profiles and weight gain. These signals suggest the thyroid axis could influence weight-loss response and subsequent regain. Levothyroxine (LT4) is widely used for hypothyroidism; evaluating its adjuvant role in obesity management is clinically relevant. This is a phase III, randomized, double-blind, placebo-controlled, multicentre clinical trial conducted in five Spanish hospitals. A total of 286 adults (25-60 years) with grade I-II obesity will be enrolled if they have subclinical hypothyroidism (TSH 5-10 mIU/L with normal peripheral hormones) or are euthyroid with TSH in the highest tertile of the reference range. Participants are randomized 1:1, stratified by age, sex, and BMI. Intervention: LT4 88 µg once daily or matching placebo for 9 months. During months 0-3, all participants receive a structured hypocaloric Mediterranean diet (≈600 kcal/day deficit; macronutrients 45% carbohydrates, 35% fats, 20% proteins) plus standardized physical-activity advice. From months 3-9, lifestyle support continues with a normocaloric Mediterranean diet. Physical-activity guidance targets ≥150 min/week of moderate-to-vigorous activity (spread over ≥3 days) and 2-3 resistance sessions/week. Primary endpoint (3 months): change in body weight (kg and %) and body composition (BMI, waist/hip circumferences, fat mass, fat-free mass, total body water by bioimpedance) comparing LT4 versus placebo under the same lifestyle program. The study is powered for n=286. Key secondary endpoints (up to 9 months): prevention of weight regain; changes in obesity stage; cardiometabolic markers (lipids, glucose/HbA1c, HOMA-IR, adipokines, inflammation, blood-pressure patterns); resting energy expenditure by indirect calorimetry; objectively measured physical activity by accelerometry; cardiac parameters (ECG) and safety; quality of life (EuroQol-5D). Mechanistic substudies assess adipose-tissue metabolic activity (gene/protein expression, browning markers, mitochondrial DNA) and explore gut microbiota, epigenetic signatures, nitrogen balance, and sex-specific differences in response. Assessments are performed at baseline and follow-up visits through 9 months and include anthropometry, bioimpedance, laboratory panels, indirect calorimetry, ambulatory blood-pressure monitoring, ECG, diet/physical-activity questionnaires, and biobanking of blood, urine, and stool; an adipose-tissue biopsy is obtained in a subsample. The trial uses intention-to-treat analyses with mixed linear models and is designed with 90% power to detect a clinically meaningful between-group difference in 3-month weight loss; total sample size is 286 (143 per arm). Overall study duration is 21 months (12 months of recruitment plus 9 months of treatment/follow-up); each participant remains in the study for 9 months. In summary, this trial tests whether adding LT4 88 µg/day to a structured Mediterranean-diet and exercise program enhances early weight loss and helps prevent regain versus placebo in adults with obesity and high-normal TSH or subclinical hypothyroidism, while characterizing metabolic mechanisms and biomarkers of response.

The ClimAIr project will expand the evidence-based understanding of climate change, air pollution, and non-communicable respiratory diseases by using Artificial Intelligence (AI) tools. It will gather data on greenhouse gases levels and disaster risks, information on serious air pollutants and respiratory diseases' prevalence. The AI powered tools will be employed to generate better intervention methods and improve public health outcomes. Federated Learning (FL) will be used to develop AI models to protect patients' privacy. By raising public awareness and delivering the ClimAIr tool - specifically designed to health workers, urban planners and policy makers - the project aims to influence policy decisions, promote healthier environments, and reduce respiratory diseases in Europe, which will be tested and validated the ClimAIr tool in specific municipalities that are part of the project. ClimAIr draws on a consortium of 21 partners from 15 European countries, including carefully selected health centres across Europe - in Spain, Luxembourg, Ukraine, Italy, France, Germany, Greece, Romania and Poland - focused on respiratory diseases, which will provide disease data and explore metabolic routes of the studied contaminants/diseases. ClimAIr is composed of an interdisciplinary team formed by research centres, ethical AI and modelling experts, SSH specialists, municipal governance, and a Communication \& Dissemination (C\&D) expert team dedicated to achieving and spread the results of the project.

Malnutrition is a common challenge in patients with pancreatic cancer undergoing cephalic pancreaticoduodenectomy (CPD), impacting postoperative recovery and overall prognosis. Nutritional support plays a crucial role in optimising metabolic, inflammatory, and digestive outcomes. This randomised, double-blind, crossover clinical trial aims to evaluate the effects of Peptamen 1.6, a hydrolysed whey protein-based enteral formula, compared to Resource HP/HC, a high-protein and high-calorie polymeric formula, in malnourished or at-risk patients with pancreatic cancer undergoing PD. The study comprises both in vivo and in vitro analyses. The in vivo component will assess the impact of Peptamen 1.6 on digestive tolerance, amino acid absorption, nutritional status, metabolic profile, inflammatory markers, and gut microbiota composition. The in vitro component will utilise human intestinal organoid models to explore how enteral nutrition formulations influence intestinal permeability and metabolism, with a focus on microbiota interactions. Primary outcomes include improvements in metabolic status, assessed through serum biomarkers (albumin, immune markers, intestinal permeability, and myosin profile), inflammatory status via peripheral blood mononuclear cells (PBMCs), and microbiota shifts in faecal samples. Additionally, adherence to treatment, digestive tolerance, and changes in body composition will be monitored using bioelectrical impedance, dynamometry, and functional mobility tests. By elucidating the mechanisms through which different enteral nutrition strategies influence clinical, physiological, and molecular parameters, this study aims to enhance personalised nutritional interventions for patients with pancreatic cancer. The findings could contribute to optimising nutritional support strategies, ultimately improving patient outcomes following CPD.

Omalizumab has demonstrated efficacy, increasing the tolerance threshold in patients with multiple food allergies, as well as reducing the risk of severe reactions when used as monotherapy. This favors improving the reactivity profile of patients with food allergy. In our setting, plant allergy caused by sensitization to panallergens such as lipid transfer proteins (LTPs) and profilins entails important limitations for the consumption of a healthy diet due to the extensive dietary restrictions. The main objective of this project is to analyze the efficacy of treatment with omalizumab administered every 2-4/weeks, used in monotherapy in patients with plant allergy due to sensitization to profilin and LTPs and those patients in whom sublingual immunotherapy with Pru p 3 (peach LTP), has not been effective, by performing a before-after study we will evaluate the changes in clinical reactivity to LTP (peach) and profilin (melon) and the changes immunological effect after omalizumab intervention. In addition, we will evaluate the changes in reactivity to at least one food other than peach and melon in the different sensitization profiles.

This study evaluates the feasibility, acceptability, and sustainability of MINDxYOU, a self-guided online psychotherapy program designed to reduce stress and improve the mental well-being of healthcare professionals in the Andalusian public health system. The trial uses a hybrid type 3 effectiveness-implementation design, combining the evaluation of implementation outcomes with observation of clinical effects on stress, anxiety, and depression. The intervention includes mindfulness, compassion, and acceptance-based practices delivered in four online modules over eight weeks. The study will be conducted in two phases: an initial hospital-based pilot and a broader rollout across primary care and hospital centers. Results will help identify how digital mental health interventions can be integrated into routine healthcare settings to support professionals working under high stress.

Dysphagia is a common complication in patients who have suffered a cerebrovascular accident (CVA), with an incidence ranging from 29% to 81%. Rehabilitation improves dysphagia in 47% of cases within the first few weeks and in 17% within 2-4 months. However, dysphagia can lead to nutritional and respiratory complications, affecting recovery and increasing healthcare costs due to the need for prolonged hospitalizations and readmissions. Malnutrition is a frequent consequence of CVA, with its prevalence increasing from 12% to 50% in patients with prolonged hospital stays. This condition worsens the vital prognosis, as it increases the incidence of complications and slows down functional recovery. Post-stroke dysphagia causes unsafe swallowing and increases the risk of aspiration, pneumonia, and other respiratory infections, worsening the patient's prognosis. Impaired swallowing efficiency leads to oral and pharyngeal residue, aggravating nutritional complications. On the other hand, swallowing safety is characterized by the presence of aspirations, manifesting as coughing, wet voice, and oxygen desaturation during the Volume-Viscosity Swallow Test (V-VST). The dietary management of these patients includes modifying food textures and using thickened liquids, strategies that have been shown to reduce the incidence of aspiration pneumonia. However, adherence to these diets is often low due to dissatisfaction with the texture and taste of thickening agents. In this context, the development of oral nutritional supplements (ONS) with stimulating flavors has been proposed to improve the perception of swallowing safety. Stimulation of the oropharyngeal sensory nerves, through activation by cold and chemical agents such as menthol, enhances swallowing by increasing oral sensitivity and improving the pharyngeal swallowing reflex response. The European Society for Swallowing Disorders (ESSD) recommends sensory stimulation as a therapeutic strategy to compensate for oropharyngeal sensory loss in patients with dysphagia. Previous studies have shown that sensory stimulation activates the swallowing center in the brainstem, accelerating the swallowing response and protecting the airway. In clinical trials with transient receptor potential (TRP) receptor agonists, observed benefits include faster closure of swallowing sphincters, improved swallowing reflex sensitivity, a 50% reduction in microaspirations, and a 67% decrease in pharyngeal residue. Based on this evidence, a new thickened ONS with stimulating flavors such as mango-mint and lemon-mint has been designed to enhance the perception of freshness and swallowing safety. This supplement is already used in clinical practice, but its effect on the perception of patients with post-stroke dysphagia has not yet been evaluated.

Pectins are dietary fibers that have shown a health effect on patients with food allergy, as they are capable of modifying the composition of gastrointestinal microbiota, and producing an immunomodulatory effect. Preliminary results by the investigators show that the intervention for 2 months with pectins produces an increase in tolerance to peach, and changes in the microbiota compared to the group of patients treated with placebo. In this project, the investigators aim to study these clinical effects and the involved mechanisms. Moreover, the long-term effect (clinical reactivity to nsLTP and immunomodulatory effect) of the dietary intervention will be prospectively evaluated 6 months after the intervention.

Background. Myocardial infarction (MI) is a leading cause of death worldwide. After MI, longterm antithrombotic therapy is crucial to prevent recurrent events, but increases bleeding, that also impacts morbidity and mortality. Giving these competing risks prediction tools to forecast ischemic and bleeding are of paramount importance to inform clinical decisions, but their current precision is limited. Improve events prediction, by discovering novel and innovative markers of risk would have a tremendous impact on therapeutic decisions and patients' outcome. Objectives. Discover novel "computational biomarkers" of risk and improve current standards of risk prediction by using innovative multidimensional information from wearable devices, biomarkers, behavioural patterns and non-invasive imaging, integrated through artificial intelligence computation. Outcomes. The primary outcomes of interest for this analysis are bleeding and ischemic events occurring in or outside the hospital at longest available follow-up. Bleeding will be categorised according to the Bleeding Academic Research Consortium (BARC) definition. The occurrence of major adverse cardiovascular events (MACE), a composite of cardiovascular death, MI, definite stent thrombosis and stroke will be collected according to the Academic Research Consortium-2 classification.

Testing a clinical decision tool (BL-Predictor)

In relation to the prognosis of vegetable FA (VFA), in contrast to other food allergies (FA), which disappear naturally with time, VFA tends to persist into adulthood and to the appearance of new sensitizations to other vegetables. The paradigm of early intervention in patients with risk factors for developing FA has changed in recent years, with evidence that maintaining a controlled diet with foods with potential allergic risk in a population of children at risk has shown efficacy in early intervention. An important aspect would be the selection of the dose of the food to be included in the diet. In this sense, recent studies on the standardization of the double-blind placebo-controlled oral challenge test (DBPCFC) in allergic patients to Lipid Transfer Proteins (LTP) with known amounts of Pru p 3 (peach LTP), have observed that the maximum tolerated dose (MTD) was equivalent to 40 grams of peach with skin. Based on these results and those obtained in the pediatric population, this study aims to evaluate whether the maintenance in the diet of a DMT evaluated in a DBPCFC could influence tolerance (desensitization) to the food at both clinical and immunological levels.

This project aims at identifying variations in breast milk neutrophils among lactating mothers with gestational diabetes or obesity (objective 1), and to describe how a dietary intervention with Omega-3 fatty acids affects these changes (objective 2). The occurrence of respiratory infections on the progeny will be analysed, as well as its development and the impact on gut microbiota and epigenetic changes (objective 3). The involvement of breast milk on the neonate's microbiota (sub-objective 1) and epigenetic variations (sub-objective 2) will be depicted. In addition, the direct engagement of milk neutrophils in the ability of the progeny to react against lung infections will be studied (sub-objective 3). To attain these mother milk and blood samples will be obtained from three groups of lactating mothers: control, obesity or gestational diabetes, upon a dietary intervention with Omega-3 fatty acids. Neutrophil populations of maternal blood and milk samples will be studied by flow cytometry and in vitro assays. The microbiome and miRNA content of infant's saliva and tool samples will be characterized by 16s rRNA gene sequencing and PCR. The occurrence of respiratory infections and the development the infants participating in the study will be tracked during the first 2 years of life by telephone surveys. To study the impact of the presented maternal variables on the progeny upon a respiratory inflammation on a systemic level, mouse models will be employed. The offspring of lactating dams with gestational diabetes or obesity will be subjected to an artificial acute lung infection. The progression of the lung disease will be studied by histology and the neutrophil profile in the organs of the litter by flow cytometry. The response to acute lung injury after fecal transplantation with infant's microbiota intro germ-free mice as well as of wild type pups breastfeed by neutropenic dams will complement the animal studies.

This trial´s aim is to assess if oral prednisone (compared to placebo), administered over five weeks is beneficial in terms of decreased total bilirubin (TBL): reduction of the peak of TBL at least 50% at 14 days or reduction in the time to normalisation of TBL value.