Clinical trials

DESIGN: A prospective, multicenter, observational cohort study including 580 patients admitted for acute decompensated heart failure (ADHF). Ultrasound assessment of congestion (VExUS and LUS) will be performed serially during admission: within 48 hours of admission, at the time diuretic therapy is switched from intravenous to oral, and on the day of discharge. The discharge assessment will serve as the primary predictor. Treating physicians will be blinded to all ultrasound findings. Patients will be followed for 90 days by telephone follow-up and chart review for the primary endpoint, with extended chart review at one year for selected secondary endpoints. AIMS: To determine whether combined ultrasound assessment of venous (VExUS) and pulmonary congestion (LUS) at discharge predicts heart failure readmission and all-cause mortality in patients hospitalized with ADHF. HYPOTHESIS: Abnormal VExUS and/or LUS findings at discharge are associated with a higher risk of heart failure readmission and all-cause mortality after 90 days. PRIMARY ENDPOINT: The primary endpoint is a composite of heart failure readmission and all-cause mortality (time-to-event analysis) after a 90-day period (chart review). Abnormal VExUS will be defined according to criteria from our ongoing validation study. Abnormal LUS is defined as ≥3 B-lines in ≥2 scanning zones per hemithorax (8-zone method) or ≥15 total B-lines overall. The primary analysis will evaluate the association between discharge VExUS and LUS findings and the risk of 90-day heart failure readmission and all-cause mortality using Cox proportional hazards regression. Models will be adjusted for age, sex, and comorbidities. SECONDARY ENDPOINTS: 1. DAOH within 90 days and one year after discharge 2. All-cause mortality within 90 days and one year after discharge 3. Rehospitalization for ADHF within 90 days and one year after discharge 4. Association between discharge VExUS and markers of congestion, including objective markers (jugular venous pressure, peripheral edema, pulmonary rales, and weight change), NT-proBNP, renal function, and echocardiographic measures of cardiac function. 5. Incremental prognostic value of discharge VExUS and LUS beyond standard clinical assessment of congestion (jugular venous pressure, peripheral edema, pulmonary rales, and weight change) for predicting 90-day and one-year heart-failure readmission and all-cause mortality. 6. Post-discharge diuretic use, defined as the change in loop diuretic dose (furosemide-equivalent) from discharge to 30- and 90-day follow-up, and occurrence of diuretic intensification (dose increase or addition of thiazide-type diuretic) within 90 days. Secondary analyses will employ Cox models for time-to-event outcomes (readmission, mortality, diuretic intensification) and linear regression for continuous outcomes (DAOH, change in diuretic dose). The relationship between discharge VExUS/LUS and post-discharge diuretic use will be evaluated both continuously (dose change) and categorically (intensification vs. no intensification). Incremental prognostic value beyond clinical and biochemical markers (e.g., NT-proBNP) will be assessed using nested model comparisons (likelihood ratio tests, AIC, C-index, NRI, IDI). INCLUSION CRITERIA: 1. Adults (≥18 years) admitted with ADHF. 2. Clinical evidence of congestion during admission, indicated by ≥1 of the following: pitting peripheral edema, ascites, elevated jugular venous pressure, or radiologic/ultrasound evidence of pulmonary congestion. 3. Treatment with ≥40 mg i.v. furosemide or equivalent dose loop diuretic during admission. EXCLUSION CRITERIA: 1. Pregnancy 2. Moribund 3. Solitary kidney 4. Inability to provide written consent

This study aims to clarify whether surgical treatment of persistent hyperparathyroidism after kidney transplantation offers clinically meaningful benefits compared with a conservative treatment strategy. Kidney transplant recipients (\>6 mo after transplantation) with persistent hyperparathyroidism (elevated PTH and either hypercalcemia or hypophosphatemia) will be randomized in a 1:1 ratio to either subtotal parathyroidectomy or conservative management according to standard clinical practice. The study is conducted as an open-label, randomized controlled pilot trial with a 12-month follow-up period. Outcomes include bone density, physical function, quality of life and symptom burden.

Quality improvement study with a quasi-randomized design. The study monitors the effect of a gradually implemented treatment algorithm prioritizing intravenous antihypertensives (e.g., nicardipine) over long-acting nitrate patches. It aims to increase the proportion of patients reaching target systolic BP \<140 mmHg within 1 hour of hospital admission while monitoring safety, clinical outcomes, and healthcare resource utilization.

Hepatitis D virus (HDV) is a major global health issue, with an estimated 12 million people living with the infection worldwide. HDV infection requires the presence of hepatitis B virus (HBV), as it relies on hepatitis B virus for replication within the liver cells. Treatment options for HDV are limited and cannot cure the infection. The combination of concurrent HBV and HDV increases the risk of developing severe liver disease, including cirrhosis and liver cancer. This risk would significantly decrease if HDV is eliminated or reduced. Consequently, there is a need for the development of new treatment options. Colleagues at Rockefeller University in New York have identified the antibody HepB mAb19, which effectively reduces the amount of circulating HBV antigens. Since HDV depends on HBV to replicate, we will test this antibody as a potential treatment for HDV. The trial design is a phase 1b open-label aiming at including 15 study participants with chronic hepatitis D infection. All study participants will receive two or three dosis of the antibody, HepB mAB19, and will be followed for 60 weeks after the first HepB mAb19 infusion. This study will evaluate the safety and pharmacokinetics of this antibody, as well as its potential effects on viral levels of HDV RNA and antiviral immune responses in individuals living with chronic HDV infection.

Glioblastoma is the most common and aggressive form of brain cancer in adults. Despite surgery, radiotherapy, and chemotherapy, most patients only live about one year after diagnosis. There is an urgent need for new and better treatments. Recent research has shown that glioblastoma cancer cells communicate with surrounding brain cells through electrical signals that help the tumor grow and resist treatment. Two existing drugs, perampanel (used for epilepsy) and senicapoc (previously tested for blood disorders), may block these harmful signals. Laboratory studies suggest that combining these two drugs could slow tumor growth and make cancer cells more sensitive to standard therapy. The SENIPERA trial will test whether perampanel and senicapoc, alone and in combination, are safe and well tolerated when added to standard treatment for newly diagnosed glioblastoma. The study will also measure how well these drugs reach the brain and tumor, and how they affect tumor biology. The study has two parts: Part A: Tests different doses of senicapoc alone to find the maximum tolerable dose. Part B: Randomly assigns patients to receive either perampanel alone or perampanel together with senicapoc. Participants will all receive standard therapy, including surgery, radiochemotherapy, and adjuvant chemotherapy. During surgery, small samples of tumor and fluid will be collected safely to study how the drugs act in the body and how tumor cells respond. Participants will be closely monitored for side effects and followed with regular clinical visits and MRI scans. The trial will take place at Aarhus University Hospital, Denmark, from February 2026 to November 2028 and will enroll 27-36 adult patients. The study aims to identify safe and biologically active treatment combinations that could be tested in larger trials to improve future glioblastoma care.

Cell- and antibody-based therapies, including chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies, represent significant advances in the treatment of hematologic malignancies. These therapies optimise the patient's immune system to target and eliminate malignant cells, achieving profound and durable responses in patients where conventional treatment approaches have failed. However, their mechanism of action-through profound immune activation-introduces a challenging toxicity profile, including cytokine release syndrome and immune effector cell-induced neurotoxicity. Emerging evidence suggests that neurotoxicity associated with these therapies may extend beyond acute symptoms to include persistent cognitive impairments. Such impairments can manifest deficits in memory, attention, executive functioning, and processing speed, potentially compromising patients' quality of life, ability to manage daily activities and return to work. The COGNITOX project explores the occurrence, clinical manifestations, and impact on quality of life of neuro-psychologically assessed and patient-reported cognitive impairment. The project's data set is generated through standardized neuropsychological tests (recommended by the International Cognition and Cancer) and validated patient reported outcome measures, to evaluate multiple cognitive domains. The project is developed in close collaboration between the Department of Haematology, Aarhus University Hospital and the Unit for Psychooncology and Health Psychology (EPoS), Department of Psychology and Behavioural Sciences, Aarhus University. The current literature on cognitive impairment secondary to cell- and antibody-based therapies is limited, and none of the studies reported so far were conducted within a Danish healthcare context. Understanding the prevalence, severity, and functional impact of cognitive impairments in this patient population is critical. These insights will inform clinical practice, guide patient counseling, and support the development of targeted interventions aimed at mitigating cognitive decline. By generating robust data, this project seeks to improve the knowledge within the field and lay the foundation for an intervention study addressing the needs of patients undergoing these advanced immunotherapies.

The aim of this study is to optimize target trough attainment while minimizing high exposures that impose increased risk of side effects such as hyperammonemia. Clinical pharmacology is based on the principle that plasma drug concentrations are linked to therapeutic effects. Therefore, understanding plasma drug concentrations is critical to balancing efficacy and toxicity in oncology treatment, as shown with Erwinase where elevated activity increases the risk of hyperammonemia. TDM can guide dose adjustments to reduce PK variability and improve outcomes. However, harnessing all information from TDM data can be challenging due to sparse and uneven sampling, and multiple sources of PK variability. Advanced analytical tools, such as pharmacometrics and population PK modelling, can address these complexities by quantifying exposure variability in patients and linking it to dosage, patient characteristics, and biomarkers. Methods: This is a NOPHO study. Within the NOPHO, Erwinase was administered intramuscularly (IM) at a dose of 20,000 IU/m² on a Mon-Wed-Fri schedule for two weeks. All non-high-risk (non-HR) patients received the same dose. HR-patients received additional Erwinase, with three doses at 2-day intervals in each treatment block. Activity levels are available from \~150 patients; among these, 20 patients received more than six doses (range: 7-42). In the A2G-1, Erwinase was administered intravenously (IV) at 20,000 IU/m², substituting one PEG-asparaginase dose with seven Erwinase doses every other day. The number of doses received varied depending on the timing of hypersensitivity reactions. Activity levels are already available from \>90 patients. Measurement of Erwinase enzyme activity levels is performed at the Asparaginase Lab in Aarhus. All samples have been analysed. The data will undergo further cleaning, validation, followed by integration with patient characteristics in a population PK model. Data Management and Security in Uppsala: All PK data will be pseudo-anonymized before being securely transferred to Uppsala University through the Allvis data portal. Data handling and formatting will be scripted in R to ensure transparency and reproducibility. Modelling will be performed on the UPPMAX computing cluster via the Swedish National Academic Infrastructure for Supercomputing. Workflow, statistics and perspectives: The modelling workflow will be performed as follows: 1. A PK model for Erwinase will be established based on asparaginase enzyme activity TDM data obtained from Nordic/Baltic ALL patients treated under the NOPHO and A2G-1. Drug clearance, volume of distribution, absorption, and bioavailability will be derived to describe the PK of both routes of Erwinase administration (IV vs IM). Nonlinear mixed-effects modelling will be applied to obtain both typical population PK parameters as well as patient variability parameters. Potential changes in parameters within patients over time will also be explored. Model development and evaluation will be conducted using NONMEM17. Model selection will be based on statistical fit and biological plausibility. Goodness of fit plots and visual predictive checks will ensure the PK model adequately describes the observed data. 2. The Erwinase PK model will be applied to explore alternative dosing strategies, as simultaneously achieving aimed target attainment (≥100 IU/L).

The aim of this sub study is to identify biomarkers in children and young adults with Acute Lymphoblastic Leukemia with hypersensitivity to PEG-asparaginase. Evidence strongly implicates humoral immunity in Asparaginase immunogenicity with neutralizing antibodies18. Asparaginase is a bacterial enzyme not naturally present in the human body, and therefore highly immunogenic. Upon administration, antigen-presenting cells internalize and present fragments of the enzyme to naïve T cells, driving their differentiation into T-helper cells signaling differentiation of B-cells. A subset of activated B-cells matures into long-lived plasma cells that home to the bone marrow, where they continuously secrete anti-asparaginase antibodies. Others differentiate into Memory-B-cells that enable rapid antibody responses. This immunological memory means that once sensitization occurs, re-exposure to asparaginase triggers strong hypersensitivity reactions that make further treatment unsafe. Yet, despite the clinical importance, only one study exists on TCR repertoire in response to anti-asparaginase antibodies, but no studies to date have directly profiled the B-cell receptor (BCR) repertoire in children with anti-asparaginase antibodies. The BCR sequencing has recently been developed. By integrating BCR-seq from blood and BM with serum proteomics (Ig-Seq), we can directly link specific plasma cell clones to circulating anti-asparaginase antibodies. This approach will provide mechanistic insight into drug immunogenicity and enable the identification of molecular biomarkers of hypersensitivity risk in children and young adults with ALL. Methods: The investigators will perform a longitudinal Danish cohort study in pediatric and young adult ALL patients receiving PEG-asparaginase as part of induction and post-consolidation therapy treated on the A2G-1. The investigators will include 20 patients with hypersensitivity and 20 without. Biological samples will be collected at baseline, during early post-exposure with PEG-asparaginase, at clinical hypersensitivity, and at follow-up timepoints according to the A2G-1. The investigators will pair these samples with EDTA-plasma samples from the same timepoints. The investigators will perform enrichment of plasma cells together with bulk TCR and BCR repertoire and clonotype sequencing. From plasma the investigators will perform serum proteomics to identify peptide fragments of circulating anti-asparaginase antibodies. Ig-Seq peptides will be aligned with BCR sequences from PBMC and BM to map specific antibodies to their clonal plasma cell origin. This approach yields a direct functional link between repertoire data and pathogenic antibodies. The investigators will compare bone marrow repertoires with blood samples to determine whether circulating clones reflect the dominant marrow-resident plasma cells. If anti-asparaginase antibodies-specific BCRs can be reliably detected in blood, this may serve as a non-invasive biomarker, reducing the need for bone marrow sampling.

Purpose of the Study: Bile duct cancers are rare and aggressive. About 250 new cases are diagnosed each year in Denmark. These cancers are difficult to detect early, so only about 20% of patients can have surgery when diagnosed. Even after surgery, the cancer often returns, and chemotherapy only slightly reduces the risk of relapse. For patients who cannot have surgery, treatments such as chemotherapy (sometimes combined with immunotherapy) can relieve symptoms and extend life, but their effect is limited. A small number of patients have specific genetic changes in their cancer that can be treated with targeted medicines. Currently, doctors cannot predict which patients will benefit from treatment. Standard monitoring methods like CT scans are expensive, inconvenient, and sometimes unreliable because bile ducts are hard to see clearly on scans. Blood tests that detect cancer DNA in the blood (called circulating tumor DNA or ctDNA) and other biological markers may be a better way to monitor the disease and adjust treatment. These tests could help detect cancer recurrence earlier and determine whether treatment is working. Measuring patients' quality of life and symptoms over time may also help predict treatment benefit and evaluate effectiveness. The goal of this study is to: * Investigate how biomarkers, including ctDNA, can predict disease course, detect relapse, and monitor treatment response. * Identify the best way to measure ctDNA in patients with bile duct cancer. * Examine whether patients' own reports of quality of life and symptoms can help assess treatment effect and prognosis. Study Design and Procedures: This is a prospective cohort study focusing on blood biomarkers and patient-reported symptoms and quality of life. Participants agree to provide blood samples: * Before treatment * During treatment * During follow-up Each sample involves up to 40 ml of blood, with a maximum of 20 samples per patient. The blood will be analyzed for: * ctDNA and genetic changes * Cancer-related markers * Inflammation markers * Immune system markers Tumor tissue samples will also be examined to compare blood and tissue results. Full genome or exome sequencing will not be performed. Samples will be stored in a research biobank. For patients with incurable disease, quality of life and symptom burden will be monitored repeatedly using Danish questionnaires. Participants: The study will include: * Up to 100 patients with potentially curable disease * Up to 200 patients with incurable disease To participate, patients must: * Have confirmed bile duct cancer * Be eligible for curative, additional (adjuvant), or palliative treatment * Be over 18 years old * Provide written and verbal consent Patients cannot participate if they: * Had another cancer within the past 5 years (except early skin cancer or very early cervical cancer) * Cannot safely provide blood samples * Are unable to cooperate with study procedures Risks and Inconveniences: Participants will have extra blood samples taken, usually during regular hospital visits. Possible side effects include mild soreness or small bruises at the needle site. The extra blood amount (40 ml per sample) is considered medically insignificant. Participants will also spend time filling out questionnaires. The number and frequency of questions have been kept as low as possible while still providing meaningful data. Financial Information: Extra costs for blood sampling, laboratory analysis, and data collection will be covered by external research funding managed by Aarhus University Hospital. The researchers have no financial interest in the project. Patients will not receive financial compensation for participating. Recruitment and Consent: Potential participants are identified during routine clinical care. During a planned meeting with a doctor, patients receive written and verbal information about the study, including its purpose, risks, advantages, and disadvantages. The conversation takes place in a calm and private setting. Patients may bring a support person. They have time to ask questions and at least 24 hours to consider participation. Patients can withdraw their consent at any time without affecting their treatment. Consent must be given before any study-related procedures begin. Publication of Results: The results - whether positive or negative - will be presented at national and international conferences and submitted to peer-reviewed scientific journals. Ethical Considerations: All participants receive standard medical treatment. The risks and disadvantages are limited, and participants are unlikely to benefit directly from the study. However, the research may improve how biomarkers and patient-reported outcomes are used to predict prognosis and treatment response, potentially leading to better treatment for future patients with bile duct cancer.

Patients with muscle-invasive bladder cancer are often older and multimorbid, thus in an increased risk of perioperative mortality and morbidity in relation to radical cystectomy (RC). The aim of the study is to investigate the effect of perioperative Comprehensive Geriatric Assessment (CGA) and tailored intervention in older, frail patients with bladder cancer undergoing RC.

In low-risk patients with stage I non-small cell lung cancer (NSCLC) surgical treatment with an anatomical resection is currently the standard of care. For medically inoperable patients with stage I NSCLC, radiation therapy is currently the standard treatment. The latest generation of radiation therapy modalities is Stereotactic Body Radiation Therapy (SBRT). In high-risk patients, minimal invasive surgery in terms of sublobar resection (wedge resection) with lymph node sampling is currently the recommended treatment approach for these patients, even though the evidence is limited. Additionally, SBRT is an alternative treatment option but the use in these patients is also based on weak evidence. So, it is highly warranted to compare these two treatment options in this group of patients in a randomized, controlled trial where selection bias can be eliminated. It is the specific aim of this study to provide such a trial allowing an evidence-based approach when deciding between surgery and SBRT as treatment for NSCLC in high-risk patients. The STRADOS study (STereotactic RADiotherapy Or Surgery) is an open randomized, controlled national multicenter study in which high-risk patients with stage I non-small-cell lung cancer (NSCLC) are randomized to receive either surgical treatment with minimal invasive wedge resection with lymph node sampling, or SBRT. The overall purpose of the study is to investigate the disease-free survival (DFS) after surgical treatment when compared to SBRT. The primary endpoint is DFS after 3 years. Secondary endpoint is quality of life after 1, 3, 6, 12 and 36 months. Tertiary endpoints are overall survival (OS) after 3 and 5 years; DFS after 5 years; re-admission adverse events and complications after 1, 3, 6, 12 and 36 months; health-care related costs within 12 and 36 months; PRO data - other than quality of life (QoL) (health condition, symptoms and functional level) after 1, 3, 6, 12 and 36 months and lung function test after 12 month.

This prospective observational study investigates the clinical utility of circulating tumor DNA (ctDNA) in patients with oligometastatic disease (OMD) undergoing definitive-intent local ablative treatment (LAT). The study aims to evaluate ctDNA as a prognostic and response biomarker before, during, and after LAT across cancer types and treatment modalities. Serial plasma samples and archival tumor tissue will be analyzed to assess ctDNA detection rates, elimination patterns, minimal residual disease, and association with recurrence, progression, and survival outcomes.

This study aims to address critical diagnostic and data gaps in tuberculosis (TB) care among pregnant and postpartum women in Guinea-Bissau, a high-burden, resource-limited setting. Recognising that current TB screening during antenatal care (ANC) relies largely on unstructured symptom questions, the study will integrate more systematic and innovative approaches into routine maternal health services. The project will implement the Bandim TBscore II as a structured triage tool to classify symptom severity and guide referrals. To strengthen diagnostic capacity, two novel tools will be evaluated: stool-based GeneXpert testing (a method recommended in children and explored here as a feasible alternative for pregnant women) and artificial intelligence-powered chest X-ray interpretation software designed to enhance TB detection where radiological expertise is lacking. The study will also generate comprehensive, population-based data on TB and TB infection (TBI) among pregnant, postpartum women and women of reproductive age in Guinea-Bissau. The results are intended to inform health policy, both locally and in high-income countries, by providing evidence to improve TB screening protocols and care for this vulnerable group. Ultimately, the study seeks to develop scalable strategies that can be replicated across low- and middle-income countries to advance maternal and child health and support global TB eradication efforts.

Quality improvement study with prospective observational design. The study monitors the diagnostic accuracy of an AI-assisted resident radiologist-termed the AI-ResRad diagnostic strategy-compared to an on-call specialist neuroradiologist-termed the SpecNeuroRad strategy-in interpreting stroke MRIs in patients with known onset. The study includes a pre-planned sub-study evaluating the diagnostic accuracy of neurologists and AI-assisted neurologists.

Observational, feasibility study investigating biological aspects in patients with liver metastasis from colorectal cancer undergoing treatment with SIRT, by translational analysis of biological samples.

The proposed study aims to evaluate the effectiveness of hypnotherapy as a non-pharmacological intervention for managing pain and anxiety during needle-related medical procedures in children aged 5 to 17 years. This research addresses a significant gap in pediatric healthcare, where painful procedures often induce distress and long-term anxiety, leading to avoidance of necessary medical care. Conventional pain management strategies primarily rely on pharmacological methods, which may pose risks and side effects. Thus, exploring safe and effective alternatives, such as hypnotherapy, is crucial.The target group for this randomized controlled trial includes children scheduled for painful procedures, such as injections or blood sampling. Participants will be randomly assigned to either the hypnotherapy group, receiving tailored sessions conducted by trained hypnotherapists, or the standard of care group, which will involve conventional pain management techniques. The study will assess primary outcomes, including anxiety levels and pain perception, before, during, and after the procedures using validated scales. Key activities of the project include conducting individualized hypnotherapy sessions, monitoring anxiety and pain levels through structured assessments, and analyzing the data to determine the effectiveness and feasibility of hypnotherapy. Secondary objectives will explore potential long-term benefits and safety concerns associated with hypnotherapy. If successful, this study could significantly enhance pediatric pain management practices, reduce reliance on pharmacological interventions, and improve the overall healthcare experience for children. The findings may also inform broader healthcare policies regarding non-pharmacological pain management strategies in pediatric settings.

This study investigates magnetic resonance-guided focused ultrasound thalamotomy (MRgFUSth) for people with Parkinson's disease (PD) and tremor not responding to conventional standard doses of dopamine replacement therapy. The aim is to identify clinical and imaging biomarkers predictive of sustained tremor control up to 24 months after MRgFUSth treatment. Participants will undergo a suprathreshold levodopa test and ¹⁸F-DOPA PET imaging to evaluate dopaminergic and serotonergic involvement in tremor. All participants will receive MRgFUSth and be followed for 24 months with standardized clinical, cognitive, and quality-of-life assessments. The study seeks to improve understanding the possible mechanisms of tremor relapse and inform patient selection for MRgFUSth in PD.

The goal of this observational study is to learn how radiotherapy for anal cancer affects the vaginal and sexual health of women after treatment. The study will also look at whether the radiation dose to the vagina is linked to the level of vaginal problems. The main questions this study aims to answer are: * How many women develop moderate or severe narrowing of the vagina after radiotherapy? * Is there a link between the radiation dose and vaginal problems? * How do vaginal changes affect sexual health and daily life? * What care and support do women receive, and how satisfied are they with this support? Participants are women aged 18 years or older who were treated with chemotherapy and radiotherapy for anal cancer and are 6 to 36 months after treatment. Participants will: Have a gynaecological examination to check the vagina for changes such as narrowing, stiffness, bleeding, or scarring Complete online questionnaires about quality of life and sexual health Answer questions about use of vaginal dilators, hormone treatment, and sexual counselling Allow researchers to analyse their radiotherapy scans to measure how much radiation the vagina received Some participants will also take part in a telephone interview about their experience with guidance and support after treatment The study will include about 80 participants across three Danish hospitals. About 20 participants will take part in the interview part of the study. The results from this study may help improve how doctors and nurses prevent, detect, and treat vaginal and sexual problems after radiotherapy for anal cancer. This may lead to better support and quality of life for future patients.

Purpose The primary aim of this research project is to evaluate whether a special blanket is an effective intervention for improving sleep among young people aged 16-24 with sleep disturbances. Sleep problems are increasingly common among Danish youth, with approximately one in five reporting significant sleep difficulties in the past 14 days. This trend has been rising steadily since 2010 and is mirrored internationally. Sleep disturbances are linked to a wide range of physical and mental health problems, including stress, anxiety, and depression, as well as negative effects on academic performance and social relationships. Early intervention is crucial to prevent chronic insomnia and poor mental health outcomes in adulthood. Current treatments include specialized psychological therapies and medication. However, psychological therapies require extensive time and commitment, and medication carries risks of side effects, tolerance, and dependency, making non-pharmacological, safe, and accessible alternatives necessary. The special blanket is believed to promote relaxation through stimulation of the tactile and proprioceptive systems. Although promising in clinical and pedagogical contexts for certain populations (e.g., children with developmental disorders and adults with neurological conditions), there is limited scientific evidence regarding its efficacy and underlying mechanisms, particularly among youth with sleep disturbances. Methods and Study Design This project is a Phase 1 randomized controlled trial (RCT) assessing the effect of 4 weeks of using a special blanket on sleep problems among young people aged 16-24, as well as the impact on participants' mental and physical health. Additionally, the study investigates possible stress-related mechanisms involved in the use of the special blanket. Following the 4-week intervention, an open-label extension phase of 8 weeks (Phase 2) will explore continued use and acceptability of the blanket. Eligible participants, screened for sleep problems, will be randomly assigned to one of three groups: Group 1: receives a special blanket (Blanket A) for home use over 4 weeks. Group 2: receives another special blanket (Blanket B) for 4 weeks. Group 3 (observation group): no blanket provided but followed for 4 weeks to monitor changes in sleep problems. The 4-week intervention phase (Phase 1) includes baseline (T1, week 0), mid-intervention (T2, week 2), and post-intervention (T3, week 4) online assessments. Sleep disturbances, physical and mental health, and stress-related mechanisms will be measured using validated questionnaires administered through REDCap. The first 40 participants in Groups 1 and 2 will additionally provide saliva samples and wear a circadian rhythm monitor (activity watch). In Phase 2, participants in Groups 1 and 2 may continue using the blanket or revert to their usual bedding. At the end of Phase 2 (T4, week 12), follow-up questionnaires will assess sleep and user experience, including satisfaction, perceived benefits, barriers, and drawbacks of the blanket. Group 3 will then be offered a special blanket for an 8-week trial. Participants The investigators aim to recruit 672 young people aged 16-24 with sleep problems. Inclusion criteria are age 16-24 years and sleep problems measured by Insomnia Severity Index (score \>10). Exclusion criteria are any underlying somatic, psychological, or neurological condition significantly affecting sleep quality; use of medications affecting sleep; pregnancy; shift work or night work; previous use of special blankets for sleep improvement and insufficient Danish language skills (questionnaires in Danish). Significance and Relevance The investigators anticipate that the findings will contribute to the current understanding of the non-pharmacological management of sleep problems, related mental and physical health outcomes, and underlying stress-related mechanisms of special blanket interventions. The results will be relevant to health professionals working with sleep problems, but also to adolescents and younger adults with sleep problems and their parents. New clinical guidelines on sleep problems in children and adolescents recommend non-pharmacological treatments as the first choice, specifically mentioning the potential efficacy of special blankets. The proposed project will help inform further development of such guidelines and related clinical practice. If special blankets are found to be effective in reducing insomnia, they could serve as an inexpensive, easily disseminated, and administered treatment with no known side effects, with the potential to greatly reduce the personal, as well as societal costs of insomnia.

Randomized, placebo controlled prospective trial evaluating the effect of denosumab on insulin sensitivity and muscle strength.

Magnetic resonance imaging (MRI) is commonly used in healthcare, and sometimes it shows small areas of brain damage called Covert Brain Infarcts (CBIs). These are usually found by chance when people have scans for things like headaches or dizziness. Although CBIs don't cause symptoms at the time, they are linked to a higher risk of future stroke and death. There is currently no standard treatment for CBIs, and doctors have different approaches-some give stroke-preventing medication (like antiplatelets or statins), while others don't treat at all. This is mostly because there isn't enough research yet. This study will test whether stroke-preventing treatments help people with CBIs. It will also look at whether having a CBI increases the risk of dementia, and whether treatment might lower that risk.

The goal of this randomized, placebo-controlled, double-blind clinical trial is to evaluate the efficacy, safety, and tolerability of cabergoline for the prevention of episodic migraine in adults with 4-14 monthly migraine days (MMD). The main questions it aims to answer are: 1. Does once-weekly cabergoline (0.5 mg or 1.0 mg) reduce MMD compared to placebo? 2. What are the effects of cabergoline on headache severity, acute medication use, and patient-reported outcomes? 3. Is cabergoline safe to use in individuals with migraine? Participants will: Complete a 4-week baseline period to document migraine frequency and classify headache days. Be randomly assigned to one of three treatment arms: 1. Cabergoline 0.5 mg/week 2. Cabergoline 1.0 mg/week 3. Placebo Participate in a 12-week double-blind treatment phase, followed by a 12-week open-label treatment phase where all participants receive cabergoline (0.5 mg or 1.0 mg once weekly). Record daily headache activity, acute medication use, and severity using an electronic diary. Complete validated headache questionnaires and provide blood samples for biomarker analysis at baseline, week 12, and week 24. The study also includes exploratory analyses of genetic predictors of treatment response and metabolic markers to assess the broader effects of cabergoline.

The study aims to test if use of autofluorescence imaging (AF) reduces the risk of developing hypoparathyroidism (hypoPT) following surgery for thyroid cancer, either total thyroidectomy (TT) or completion hemithyroidectomy (cHT).

As estimated by the WHO 10.6 million new Tuberculosis (TB) cases were identified in 2022- while more than three million went undetected and untreated. The low detection rate illustrates the failure to recognise and diagnose TB in the current cascade of healthcare and is a major obstacle to effective TB control programs. This multi-centre cluster-randomised clinical trial will evaluate the effect (i.e., diagnostic yield) of improving the point-of-care diagnostics already in place in most primary health-care centres in low-resource settings. The present study will be conducted in two different geographical settings in the Western and Eastern African countries of Guinea Bissau and Ethiopia. This improved clinical diagnostic pathway may improve case detection rates at primary healthcare level, ensuring prompt commencement of treatment, thereby diminishing transmission risk in the community and improving treatment outcomes. The Optimized Diagnostic Procedure (ODP) will utilize instructed sputum sampling and pooling as well as computer-aided detection (CAD) chest X-ray (CXR) and additional pooled sputum sample as well as non-sputum sampling (faecal and a buccal/tongue swab and saliva) for GeneXpert Ultra PCR (Xpert) as state-of-the-art add-ons to the routine diagnostic pathway for TB. This adds to the key components of the WHO "End TB" strategy - early diagnosis - and if successful, may be rapidly approved by the WHO and implemented by governments globally with potentially major public health benefits. The study will be conducted in close liaison with the national Ministries of Health and TB programs in Guinea-Bissau and Ethiopia. This will facilitate any relevant findings to be taken forward for implementation into policy and practice. Capacity development, training and educational activities will be closely aligned to this study.

The goal of this clinical trial is to examine the effect of limb occlusion therapy (remote ischemic conditioning, RIC) in subjects with aneurysmal subarachnoid hemorrhage. The main question it aims to answer is whether RIC can improve long-term recovery in participants with aneurysmal subarachnoid hemorrhage. Researchers will compare levels of functional independence in participants in the RIC-group to participants in the sham-group.