Clinical trials

The aim of this study is to identify HRV changes predictive of IBD flares using patient-own wearable devices in a large cohort supplemented by additional data layers including sleep parameters, step count and clinical data extracted from electronic patient files.

To compare postprandial plasma amino acid availability, expressed as incremental area under the curve (iAUC), over a 6 hour period following ingestion of 25 g of different protein isolates in healthy, young adults. The primary objective is divided into the following 2 sub-studies, each with 3 comparisons: * Sub-study 1: whey protein, calcium caseinate, sodium caseinate. * Sub-study 2: calcium caseinate, magnesium caseinate, potassium caseinate.

Plant stanols are known to lower low-density lipoprotein cholesterol. However, studies have suggested that these compounds also influence the immune system. Asthmatic responses are predominantly T helper (Th)2 cell dependent, while plant stanols were previously found to activate Th1 cells and shift the immune response away from the Th2 cell dominant asthmatic response. The question now is whether this also translates into a reduction of clinical symptoms in asthma patients.The primary objective of this study is to demonstrate clinical benefits of prolonged consumption of plant stanols (delivered via plant stanol esters) in asthma patients. The secondary objectives are to evaluate the mechanisms via which plant stanols modulate the immune system and to evaluate the effects of plant stanol ester consumption on cardiovascular (CVD) risk parameters.

The goal of TAILOR-HF is to integrate clinical data, laboratory parameters, treatment patterns, and circulating biomarkers to identify factors that predict individual response to pharmacological treatment in patients with heart failure. TAILOR-HF is an observational study with protocol-mandated assessments scheduled at baseline and at 1, 3, and 6 months after enrolment. Additional follow-up data will be collected through telephone visits every 6 months until the last participant has completed the protocol-mandated 6-month visit.

The goal of this clinical trial is to learn whether autologous fat transfer (AFT) is as effective and safe as Deep Inferior Epigastric Perforator (DIEP) flap breast reconstruction in irradiated breast cancer patients following mastectomy. It will also evaluate patient satisfaction, quality of life, complication rates, and cost-effectiveness of both reconstruction techniques. The main questions it aims to answer are: Does AFT result in non-inferior patient satisfaction with the reconstructed breast compared to DIEP flap reconstruction 12 months after the final operation? Does AFT result in fewer major complications and improved cost-effectiveness compared to DIEP flap reconstruction? Are quality of life outcomes and oncologic safety comparable between AFT and DIEP flap reconstruction in irradiated patients? Researchers will compare AFT to DIEP flap reconstruction to see if AFT can provide similar reconstructive outcomes with lower morbidity and fewer complications in irradiated breast cancer patients. Participants will: Undergo breast reconstruction using either AFT or DIEP flap reconstruction Attend follow-up visits for clinical examinations, imaging, and assessment of complications Complete questionnaires about breast satisfaction, quality of life, and recovery during follow-up Be monitored for oncologic safety and reconstructive outcomes for 12 months after the final operation

The goal of this proof-of-concept clinical study is to determine the effect of combining osimertinib with febuxostat on cerebrospinal fluid concentrations of osimertinib in patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC). The main question it aims to answer is: what is the effect of combining osimertinib with the ABCG2 inhibitor febuxostat on cerebrospinal fluid to unbound plasma osimertinib concentration ratio in patients with EGFR mutated NSCLC without central nervous system (CNS) metastases and without the ABCG2 34G\>A single nucleotide polymorphism (SNP)?

Narrowing of the carotid artery due to atherosclerosis with an unstable plaque can cause a stroke. Patients with carotid artery disease who have had a TIA or minor stroke and are at high risk of another stroke are often treated with surgery or stenting to remove the plaque. For lower-risk patients, medication alone is the better option, as surgery also carries risks. A new decision method, based on MRI detection of unstable plaques (IMPROVE), can better assess stroke risk and help determine which patients do or do not need surgery. We are investigating whether this method is at least as effective as the standard approach, which mainly considers the degree of narrowing. We expect that this new method will help reduce strokes and lower healthcare costs. Patients will be followed for several years to compare which method is better for health and costs.

The purpose of the Bleeding Disorder of Unknown Cause in the Netherlands study (BDUC-iN) is to learn more about unexplained bleeding in individuals with a bleeding disorder of unknown cause (BDUC). The study aims to better understand why these individuals have increased bleeding and how it affects their health and daily life. The main questions of this study are: 1. What are the mechanisms underlying the bleeding tendency in BDUC? 2. How do bleeding symptoms affect patients' daily functioning and overall health-related quality of life? 3. How is care delivered to individuals with BDUC, and how can this be improved? Participants with increased bleeding tendency who remain undiagnosed after standard coagulation testing and are consequently classified as having BDUC will be enrolled across the Hemophilia treatment centers in the Netherlands. Participants will undergo blood sampling for advanced hemostasis testing and genetic analysis. In addition, participants will complete validated questionnaires to assess bleeding symptoms and health-related quality of life. Participants will be followed longitudinally to evaluate how bleeding symptoms affect daily activities, medical procedures, and overall health-related quality of life.

The purpose of this study is to assess the digestion and absorption kinetics of beef consumed alone or as part in healthy adults. In a randomized, crossover design, 10 young, healthy adult males and females aged 18-35 years, will consume a meal consisting of 25 g protein from minced beef alone or as part of a mixed-meal during two separate experimental trials. The main study endpoint is the exogenous rate of amino acid appearance in response to the ingested beef over a 10-h period.

A single arm phase II study evaluating intracranial efficacy of tarlatamab in patients with asymptomatic active brain metastases from small cell lung cancer (SCLC).

The purpose of this study is to assess the optimal protein intake to maximize whole-body protein net balance in healthy adults. In a randomized, double-blinded, crossover design, 12 young, healthy adult males and females aged 18-35 years, will consume a test diet consisting of free amino acid mixtures based on milk protein that vary in protein content 7 separate acute metabolic trials. The main study endpoint is optimal protein intake based on the lowest protein intake that maximizes whole-body protein net balance.

The purpose of this study is to assess the amino acid oxidation dose-response relationship of ingested whole-food protein in healthy adults. In a randomized, crossover design, 20 young, healthy adult males and females aged 18-35 years, will consume a dinner consisting of 0.32, 0.74, and 1.32 g protein･kg BM-1 (corresponding to 1, 2, and 4 minced beef patties, respectively) during 3 separate experimental trials.The main study endpoint is the amino acid oxidation of ingested protein over a 24-h period.

Basal cell carcinoma (BCC) is the most common skin cancer in the Netherlands, with incidence rates continuing to rise. The current diagnostic standard combines clinical evaluation and dermoscopy, while biopsy followed by histopathological examination remains the gold standard when uncertainty about the diagnosis persists. However, biopsy is invasive, time-consuming, and costly. Line-field confocal optical coherence tomography (LC-OCT) is a non-invasive imaging technique that has emerged as a promising alternative to biopsy for BCC suspected lesions. This retrospective study aims to evaluate the real-world clinical performance of LC-OCT in routine dermatological practice, where it has been integrated into the diagnostic work-up for BCC-suspect lesions.

Rationale: Healthy foods, including mixed nuts, may improve brain function, which is essential for cognitive and metabolic health, and may contribute to improved food intake regulation. It is therefore important to investigate the specific effects of walnuts on cerebral blood flow responses before and after intranasal insulin administration, as well as their associated functional benefits. The investigators hypothesize that long-term walnut consumption improves vascular function and insulin-sensitivity in the brain, thereby enhancing cognitive performance and appetite control in abdominally obese men and women. Objective: The primary objectives are to investigate in abdominally obese adults the effects of 24-week walnut consumption on (regional) vascular function and insulin-sensitivity in the brain, while the investigators will also assess changes in cognitive performance and appetite-related brain reward activity (secondary objectives). Cerebral blood flow responses before (brain vascular function) and after the administration of intranasal insulin spray (brain insulin-sensitivity) will be quantified by the non-invasive gold standard magnetic resonance imaging (MRI)-perfusion method Arterial Spin Labeling (ASL). Study design: This intervention study will have a randomized, controlled parallel design. The total study duration will be 24 weeks. Study population: Fifty-five abdominally obese men and (postmenopausal) women (aged 45-75 years) without a history of cardiovascular diseases or complaints will participate. This study population is expected to have a decreased cerebral blood flow at baseline and are also at increased risk of cognitive impairment, allowing for improvement by the intervention. Intervention: Study participants will receive daily 50 g (about 15% of energy) of raw walnuts (walnut intervention) or no walnuts (control intervention) for 24 weeks. Main study parameters/endpoints: At baseline and after 24 weeks (follow-up), participants will visit the research facilities for assessments. The primary endpoint is the difference in the cerebral blood flow response before and after intranasal insulin administration between the walnut and control intervention. Cognitive performance will be assessed, while the investigators will also focus on appetite-related brain reward activity (secondary outcomes).

This study will investigate the effect of providing a daily ketogenic nutritional supplement in the evening for a prolonged time (4 weeks) to induce a mild ketogenic state during the night in healthy elderly (60-80 years), overweight/obese (BMI: 25-35 kg/m2) individuals with low physical activity, on 24h rhythmicity in energy metabolism as compared to a non-ketogenic, isocaloric control.

Nutrition is very important to keep blood sugar levels balanced. If blood sugar levels are too high, it can lead to diseases such as cardiovascular disease and type 2 diabetes (T2DM). Therefore, adjusting what one eats, also called a diet or nutritional intervention, can help prevent these diseases. However, not everyone responds the same to a diet. In about 30% of people, a diet does not work as hoped. This can be due to various reasons, such as a person's metabolism, genetic predisposition, the composition of the food one eats, or the bacteria in the intestines. Everyday things like sleep, stress, and movement also play a role. The investigators used a computer model to classify people with overweight and obesity into groups based on these factors. The investigators call such a group a 'Metabolic Phenotype', or in short 'Metabotype'. Based on the Metabotype, a personalised diet was developed (personalised nutrition intervention) that may better suit each person's unique situation. The investigators hypothesize that a precision nutrition intervention, tailored to Metabotypes identified through unsupervised clustering (using the aforementioned computer model) of predefined, accurate features related to cardiometabolic health-specifically, tissue-specific glucose and lipid metabolism and detailed body composition-will enhance blood glucose homeostasis, reduce cardiometabolic risk, and improve adherence to the intervention and mental well-being, compared to population-based dietary guidelines. The present project will contribute to targeted and efficient precision-based dietary strategies for individuals at increased risk of T2DM.

Background: Prostate cancer is the second most common cancer and the fifth leading cause of death in men worldwide. Tumour growth is attributed to disproportionately greater protein synthesis rates relative to protein breakdown rates. Tumour protein synthesis is modulated by several factors, including energy availability, blood flow, and hormone concentrations (e.g., IGF-1). Lifestyle modifications are rapidly becoming recognized as important adjunct therapeutic approaches to slow cancer development and enhance treatment efficacy. Dietary energy restriction is a 30-50% reduction in food intake, which induces an energy deficit and has been shown to attenuate tumour growth in rodent models. Muscle mass often declines during cancer treatment and negatively impacts treatment success rates and recovery. One drawback to dietary energy restriction is that it may accelerate declines in skeletal muscle mass and strength in cancer patients. Exercise also induces an energy deficit by increasing energy expenditure. In addition, exercise alters blood flow and releases circulating molecules, which appear to lower tumour protein synthesis rates. Exercise increases muscle protein synthesis rates, which would provide further benefits to cancer patients by helping to maintain skeletal muscle mass. Despite their promising therapeutic properties, the clinical efficacy of dietary energy restriction and exercise has not been directly determined in vivo in cancer patients. Hypothesis and Objectives: The objective of this study is to compare the impact of dietary energy restriction versus (isocaloric) daily exercise on muscle, prostate, and prostate tumour protein synthesis rates over a 7-day period in vivo in prostate cancer patients. It is hypothesized that 1) dietary energy restriction will lower both prostate tumour and muscle tissue protein synthesis rates and that 2) daily exercise will lower prostate tumour protein synthesis rates but increase muscle protein synthesis rates in prostate cancer patients. Setting and Methods: Forty-five prostate cancer patients scheduled to undergo radical prostatectomy will be randomly assigned to one of three groups. The first group will undergo 7 days of dietary energy restriction (40% less food intake). The second group will perform 7 days of daily exercise and mild dietary energy restriction resulting in a total energy deficit of 40%. The third group will follow their regular diet and physical activity (control group). The research team will provide all aspects of the intervention (standardized meals, personalized exercise supervision). Patients will ingest deuterium-labelled water (2H2O) throughout the intervention period. After 7 days, patients will undergo a radical prostatectomy, during which tumour tissue, skeletal muscle tissue, and blood will be collected. Deuterium (2H-alanine) incorporation into the tissue samples will be measured to assess prostate tumour and skeletal muscle tissue protein synthesis rates.

The goal of this randomized controlled trial is to compare the effectiveness and cost-effectiveness of lymphaticovenous anastomosis (LVA) with sham surgery for patients suffering from unilateral cancer-related lymphedema in either the upper or lower extremity. It aims to answer whether LVA is more effective than sham surgery in terms of improvement in Lymph-ICF score. A total of 110 participants will be allocated randomly into two groups at a 1:1 ratio. The first group will receive lymphaticovenous anastomosis (LVA), while the second group will undergo sham surgery.

Disturbances in brain insulin sensitivity are associated not only with obesity and type 2 diabetes, but also with brain aging and cognitive decline. Longitudinal studies suggest that dietary patterns, particularly those high in dairy intake, may impact brain function via the gut-brain axis. Indeed, dairy foods are known to modulate gut microbiota and may, through this pathway, not only improve brain insulin sensitivity and cognitive performance, but also mental health and appetite regulation. However, underlying mechanisms remain largely unexplored. The primary objective of this study is to evaluate, in older adults with overweight or obesity, the effects of a high-dairy food pattern (4-5 daily servings of (butter)milk, cheese, yogurt, or cottage cheese) compared to a low-dairy food pattern (≤1 serving daily) on (regional) brain vascular function and insulin sensitivity. These outcomes will be quantified using the non-invasive MRI perfusion technique Arterial Spin Labeling (ASL), which assesses cerebral blood flow (CBF) in response to intranasal insulin, a validated physiological marker of brain insulin sensitivity. Secondary objectives include changes in cognitive performance (via the CANTAB neuropsychological test battery), gut microbiota composition (via shotgun metagenomic analysis of fecal samples), and appetite-related brain reward activity (via BOLD-fMRI with food cues). Exploratory analyses include conventional cardiometabolic risk markers (blood pressure, lipid and glucose metabolism), and perceivable (consumer) benefits.

Rationale: Sedentary behavior (SB) has been associated with impaired cognitive function in elderly, and negatively impacts glucose metabolism. Interrupting sitting with physical activity (PA) bouts may exert beneficial effects on cognitive function via an improved glucose metabolism. Nevertheless, the impact of breaking up prolonged sitting with various frequencies of PA bouts remains unexplored in young sedentary adults. Moreover, we hypothesize that the pattern of the breaks modifies the effects. Thus, randomized controlled trials (RCTs) are highly needed to investigate the effects of interrupting sitting with different frequencies of PA on cognitive function and glucose metabolism. We now hypothesize that interrupting sitting with different frequencies of walking breaks differentially affects cognitive function and glucose metabolism. Objective: The aim is to investigate the effects of breaking up sitting with different frequencies of PA bouts on cognitive function and glucose metabolism in young sedentary adults. Study design: A randomised, controlled cross-over study will be performed, consisting of four interventions in a counterbalanced order: uninterrupted prolonged sitting, short breaks, moderate breaks, and long breaks. Intervention: Participants will complete four conditions in a randomized, counterbalanced order: sitting (uninterrupted prolonged sitting without any interruptions), short breaks (walk 1 minute every 10 minutes), moderate breaks (walk 3 minutes every 30 minutes), and long breaks (walk 27 minutes during the intervention). Each condition lasts 4.5 hours.

After severe traumatic brain injury, adequate blood flow to the brain is essential for recovery. This depends on arterial blood pressure, yet intensive care units apply fixed targets to all patients - treating every brain and patient the same. This study aims to change that. With new technology, 'optimal' blood pressure can be determined for each individual brain and treatment can be tailored accordingly. This personalized approach to neurocritical care has never been tested in a randomized controlled study before. If effective in showing reduced brain damage biomarkers, it will fundamentally transform brain injury treatment and dramatically improve recovery outcomes for patients worldwide.

Hospitalization often involves long periods of bed rest and reduced nutritional intake, which can lead to skeletal muscle loss and anabolic resistance. These effects slow recovery and increase the risk of complications, long-term disability and healthcare costs. Animal-based proteins are effective at stimulating muscle protein synthesis (MPS) because they contain all essential amino acids and have high bioavailability, but they are less sustainable. Plant-based proteins are more environmentally friendly but may be less effective for MPS due to lower essential amino acid content and lower digestibility. Combining different plant proteins may improve their quality, yet their impact during bed rest is still unclear. Neuromuscular electrical stimulation (NMES) may help counteract anabolic resistance by mimicking exercise, but its long-term effects in bedridden individuals are not well studied. This prospective, randomized, controlled trial aims to assess the effects of a nutritional intervention (plant-dominant versus dairy-based protein) and a physical stimulus (NMES versus non-NMES) on MPS during 4 days of bed rest in healthy young adults.

Critically ill patients, such as those with trauma or sepsis, experience high rates of malnutrition (up to 75%). Malnutrition worsens outcomes by increasing infection rates, hospital stays, mortality, and healthcare costs. Adequate nutrition is therefore crucial in the ICU. To ensure appropriate nutrition, accurate determination of total energy expenditure (TEE) is essential. In practice, predictive equations are often used, but these can misestimate TEE in ICU patients due to complex metabolic changes. Indirect calorimetry is recommended but limited by technical constraints. Consequently, the doubly labeled water (DLW) method, though expensive, offers a precise and non-invasive way to measure TEE over time. This study applies the DLW method in ICU patients to improve energy assessment and guide personalized nutrition strategies that support recovery and outcomes.

Rationale - Critically ill patients often experience severe skeletal muscle wasting due to an imbalance between muscle protein synthesis (MPS) and degradation, contributing to long-term impairments such as ICU-acquired weakness (ICU-AW) and post-intensive care syndrome (PICS). Effective interventions to mitigate muscle wasting remain a critical unmet need. Protein intake has been identified as a potential modulator of MPS, but anabolic resistance and conflicting evidence regarding optimal protein intake necessitate further investigation. Objective/Hypothesis - This study aims to evaluate the effect of a normal (target: 0.8 g protein/kg/day) versus elevated (target: 1.3 g protein/kg/day) protein intake on MPS rates over four days in critically ill patients. Population - 26 critically ill patients who are suitable for enteral nutrition, mechanically ventilated (min 3 days), and stay at the ICU for at least 7 days will be included. Method: Patients are randomly assigned to two groups (normal or higher protein intake). Muscle biopsies and blood samples will be collected to assess muscle protein synthesis rates.

The purpose of the study is to evaluate whether the distribution pattern of daily protein intake affects how much muscle protein can be built in the muscle after resistance exercise and at rest.