Clinical trials

Rationale: Postamputation pain (PAP) is frequently seen after amputations and is a severe lifelong disabling condition affecting quality of life (QoL). Different nerve surgical techniques are available to treat PAP if non-surgical treatment options are not sufficient. Multiple techniques have been described for treatment of symptomatic neuromas with varying results. Techniques described include traction neurectomy with/without implantation, nerve grafting, nerve capping, regenerative peripheral nerve interface, and targeted muscle reinnervation (TMR). In the Leiden University Medical Center (LUMC), the most common techniques to treat painful neuromas include TMR and fascicular split (FS). TMR involves coaptating the transected mixed nerve to functional motor nerves, showing promising results in recent studies. FS is a technique closely related to neurectomy with implantation in a functional muscle. The difference is that with FS, the nerve is split into fascicles before implantation to allow for better distribution of nerve fibers. These techniques have not yet been compared. In this study, the investigators will compare both these techniques in a prospective setting for the treatment of PAP. The hypothesis is, that after 12 months, pain will be diminished and QoL will be increased in all patients versus the pre-operative status. There will be little to no difference in outcome between the surgical techniques used. Objective: To evaluate limb pain in patients with intractable postamputation pain (residual limb pain and phantom limb pain) one year after nerve embedding surgery following the standardized workup of the LUMC. Study design: Prospective study Study population: Patients 18 years of age or older, with a history of more than 6 months of intractable postamputation neuropathic limb pain, with no history of previous surgical intervention for pain treatment, referred to the Leiden Nerve Center. Main study parameters/endpoints: The mean difference in pain scores for phantom limb pain and residual limb pain one year postoperatively. An average pain score from the past 7 days is used for PLP and RLP individually, on the 11-point (0-10) numerical rating scale (NRS). Additionally, the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Behavior and Interference Questionnaire Short Forms (7a and 8a, respectively) are used one year postoperatively. Nature and extent of the burden and risks associated with participation, benefit, and group relatedness: Both techniques are currently used in the Leiden University Medical Center (LUMC) and considered standard of care. The decision to perform either technique is solely dependent on the personal preference of the treating nerve surgeon. The results of this trial will improve the understanding of the treatment effect of both surgical techniques with a minimal patient burden. Participation requires patients to complete 3-4 non-invasive questionnaires about pain, quality of life, depression and anxiety, and mobility over a period of 2 years. The pre-operative (if applicable) and 12-month postoperative questionnaire will each take approximately 15 minutes to complete. The other two questionnaires at 18 and 24 months postoperative will take approximately 3-4 minutes to complete. Additionally, participants will fill out a daily questionnaire consisting of one to three questions about pain for 7 consecutive days at 12 months.

The RAINBO umbrella program consists of four clinical trials investigating new adjuvant therapies in endometrial cancer patients. Eligible patients will be assigned to one of the four RAINBO trials based on the molecular profile of their cancer: * p53 abnormal endometrial cancer patients to the p53abn-RED trial * mismatch repair deficient endometrial cancer patients to the MMRd-GREEN trial * no specific molecular profile endometrial cancer patients to NSMP-ORANGE trial * POLE mutant endometrial cancer patients to the POLEmut-BLUE trial

This study aims to evaluate the feasibility of Laser Speckle Contrast Imaging for perioperative perfusion assessment of the lower extremity before, during, and after revascularization.

The goal of this clinical trial is to determine whether belimumab can improve detection of circulating HLA-specific memory B cells to support safer and more effective donor organ allocation in highly sensitized kidney transplant candidates. The main questions it aims to answer are: Does treatment with belimumab change the antigen specificity profile of circulating HLA-specific memory B cells compared to pre-treatment measurements? Does a delisting strategy that incorporates mobilized memory B cells improve the probability of donor organ allocation and reduce time to transplantation? Participants will: Receive a short course of belimumab treatment Provide blood samples before and during treatment to assess memory B-cell profiles Undergo evaluation for potential adjustment of unacceptable HLA specificities (delisting) based on test results Be followed for donor organ allocation and transplantation outcomes

Rationale: Aneurysms of different types are known to be associated. In literature, concurrence of intracranial- and aortic aneurysms is described. Screening for aortic aneurysms (AA) in patients with intracranial aneurysms (IA) or aneurysmal subarachnoid haemorrhage (aSAH) could be cost-effective and of significant importance to decrease morbidity and mortality. The available literature on the association between the two types of aneurysms is sparse and in general of poor methodological quality. This protocol presents a study to more adequately evaluate the association between IA and AA. Objective: To investigate the occurrence of abdominal aortic aneurysms (AAA) in patients who experienced aSAH. Study design: This single cohort prospective study will include patients who experienced aSAH. The study participants will receive an abdominal ultrasound of the aorta to detect an AAA. Study population: aSAH patients from a prospective cohort trial in the Netherlands. Main study parameters/endpoints: The primary outcome, which will be investigated in the here above described study population, is the number of AAA detected on abdominal ultrasound. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients will not receive an intervention, but only a diagnostic imaging without radiation. The burden associated with this study are considered minimal and the risks negligible. An abdominal ultrasound is a non-invasive diagnostic method with no risks for the participant. The only possible existing burden to the participant is travel and appointment time with a risk of detecting an abdominal aortic aneurysm or other (occult) intra-abdominal pathologies. When an aneurysm, sub-aneurysm or other intra-abdominal pathology is detected, surveillance or treatment according to standard of care and guidelines will follow.

The goal of this clinical study is to assess differences in collaborative efforts to make care fit between clinical encounters in usual care and those using the Making Care Fit tool among young adults with type 1 diabetes and their clinicians. The main question it aims to answer is: What are the differences in collaborative efforts to make care fit between clinical encounters in usual care and those using the Making Care Fit tool? Researchers will compare clinical encounters in usual care with encounters supported by the Making Care Fit tool to examine differences in collaborative efforts to align care and daily life. Participants will: * Take part in an observed clinical encounter with their clinician * Participate in a post-encounter video-stimulated interview reflecting on the consultation * Complete questionnaires about their experiences of the consultation

The IMPRoVE study is a prospective, non-interventional, explorative cohort study to determine prognostic immune markers in patients with epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer (EOC).

This real-world, international registry aims to evaluate the current experience with sodium-glucose cotransporter 2 inhibitors (SGLT2i) in adult congenital heart disease (ACHD) patients by investigating the prescription patterns, safety, tolerability, and potential beneficial effects on heart failure-related outcomes.

Rationale: In current clinical practice, polypharmacy and patient empowerment are critical yet often overlooked. Polypharmacy, the chronic use of five or more drugs, poses risks such as adverse drug reactions and decreased medication adherence, especially in elderly and multimorbid patients. Despite the interconnected nature of drug-drug and drug-gene pro inter-actions, they are considered separately. Ignoring these interactions can be hazardous, yet clinical trials to investigate them are infeasible due to fast-growing complexity, variability among patients, high costs associated with large-scale studies, and ethical and logistical chal-lenges. Consequently, there is a substantial knowledge gap in managing complex medication regimens in real-life scenarios and providing guidelines to enhance patient empowerment and drug safety. The SafePolyMed project aims to develop a patient-centred framework to define, assess and manage drug-drug, drug-gene and drug-drug-gene interactions. This framework, a web-based medication management centre, will support patients in managing their therapy-related health data, enhancing education and empowerment, and improving patient safety. Objective: To assess the impact of the developed medication management centre on patient empowerment in polypharmacy patients, thereby improving drug safety. Secondary objec-tives are to explore if the tool is able to identify patients at risk for a drug-drug-gene interaction and lower the adverse drug event rate. Study design: The study is a proof of concept study conducted at four institutes located in Germany, Greece, Slovenia and The Netherlands. Polypharmacy patients will use the medi-cation management centre (MMC), which provides curated, patient-specific information about drug interactions and PGx. To assess patient empowerment, patients will receive ques-tionnaires during a 12 week follow-up period. Study population: 120 subjects with polypharmacy (defined as the chronic use of 5 or more drugs) of at least 18 years of age, with a first prescription for one of 10 index drugs. The study will be performed at 4 different sites (Leiden (NL), Patras (GR), Ljubljana (SL), Aachen (DE)) to represent different clinical settings across Europe. Each site will recruit 30 patients. Intervention: The MMC that provides patient centred information on drug-drug interactions and pharmacogenetics affecting personal polytherapy. The MMC will show a selection of high quality publicly available information such as details on different types of medications, includ-ing their uses, side effects and instructions for use, in the language of the patient. This infor-mation is targeted at an individual patient's medication profile to inform patients to better un-derstand and deal with their personal health information, with regard to drug therapy. Patients in the Netherlands, Slovenia and Greece also will receive their PGx profile to further personal-ise the MMC experience. Main study parameters/endpoints: The primary outcome is the sense of empowerment and health literacy for participants before and after use of the MMC. Secondary outcomes include an evaluation of the drug-drug-gene interactions and adverse drug events in the study popula-tions compared to matched historical controls. Nature and extent of the burden and risks associated with participation, benefit, and group relatedness: Patients are exposed to the regular treatment. In addition, patients will receive questionnaires at baseline, two, and twelve weeks regarding the use and experience of the medication management centre, and a close-out interview at week twelve. In addition, 10ml of blood will be collected during a venipuncture for pharmacogenetic analyses. Benefits include having access to the medication management centre for the duration of the study. Additionally, patients will receive their PGx profile. This can be used to individualize drug treatment, based on the Dutch Pharmacogenetics Working Group (DPWG) guidelines. Overall, minimal risks are expected for subjects as they will receive normal clinical care. In-formation from the MMC will be a curation of existing publicly available data. Any information regarding DDIs and DGIs will be supplemented with a disclaimer that the patient should not adjust their treatment without talking to a healthcare provider.

The goal of this observational study is to measure effort using esophageal pressure measurements, oxygen consumption and diaphragm activity in mechanically ventilated Intensive Care Unit patients during a Spontaneous Breathing Trial. The main question aims to answer whether the sEMG signal derived from the SERA device, effort parameters and oxygen consumption have an association with weaning failure. Participants will be measured while performing a spontaneous breathing trial.

The goal of this clinical trial is to evaluate the efficacy of low sodium oxybate (LXB) (brand name Xywav) in the treatment of (nocturnal) cluster headache attacks in subjects with chronic cluster headache. It is an 16 week, randomized, double-blind, placebo- controlled, bi-center trial. LXB will be administered as a twice nightly regimen. All subjects will undergo an 6 week Treatment Titration and Optimization Phase. The main trial endpoint is the change from baseline in average weekly frequency of nocturnal cluster headache attacks over 4-week fixed stable dose of treatment period.

Background: \- The effect of repeated GON-injections has never been studied in a double-blind randomized trial as a prophylactic therapy in a well-documented group of chronic patients. As such, (repeated) GON-injection has not yet found its place in current (inter)national treatment protocols for chronic cluster headache. Objectives: \- The primary objective is to determine if repeated GON-injection result in effective control of cluster headache attacks for more days compared to placebo in chronic cluster headache. Eligibility: \- Patients will be selected from the LUMC (Leiden University Medical Center) and CWZ (Canisius Wilhelmina Hospital) chronic cluster headache populations, diagnosed based upon the ICHD-3. Design: \- Bi-centre, randomized, double-blind, placebo-controlled retention trial with a maximum follow-up of one year.

The aim of the study is to perform a clinical validation of the analytical method for dried blood spot microsampling of cabozantinib, pazopanib, sunitinib, lenvatinib, imatinib, abiraterone, enzalutamide, nivolumab, ipilimumab, pembrolizumab, atezolizumab, bevacizumab or enfortumab vedotin. The secondary objective is to test the feasibility of home monitoring (microsampling TDM) of cabozantinib, pazopanib, sunitinib, lenvatinib, imatinib, abiraterone, enzalutamide, nivolumab, ipilimumab, pembrolizumab, atezolizumab, bevacizumab or enfortumab vedotin in oncology patients.

Smart technology could improve quality of care in patients who have been admitted to the ICU and have been discharged from ICU and hospital, by early diagnosis of complications and early (ambulatory) treatment. With the ICU-Recover Box and its smart technology the investigators see new opportunities to improve patient health and to recognize early if escalation of medical care is needed. The primary objective of the pilot study is to assess the feasibility of the use of smart technology by persons that have been discharged from the ICU in the twelve months following ICU discharge.

The goal of this study is to compare postamputation pain (phantom limb pain and residual limb pain) one year postoperatively in patients who received a lower extremity amputation (LEA) with standard nerve handling (neurectomy) versus those who received Targeted Muscle Reinnervation (TMR). Patients between 18 and 75 years old, scheduled for an LEA (transfemoral to transtibial) as a primary or secondary sequela of vascular disease, are randomized into standard neurectomy or TMR. TMR is a frequently studied surgical technique and prevents neuroma formation by rerouting a cut mixed nerve end to a functional motor nerve. The investigators hypothesize that TMR during amputation surgery will significant improve PostAmputation Pain (PAP), quality of life, participation in family life and society, and reduction of health-related costs. Participants will be asked to complete multiple online questionnaires postoperatively regarding these outcomes at five evaluation moments (at 2 weeks, and at 3, 6, 9, and 12 months).

Mixed aortic valve disease (MAVD) is defined as the combination of aortic valve stenosis (AS) and regurgitation (AR) and is relatively frequent, with a reported prevalence up to 20-30% of patients with aortic valve disease. Mortality of patients with moderate MAVD (coexistence of both moderate AS and moderate AR) is largely unknown, and therefore there are currently no guidelines-based indications for surgical or transcatheter intervention for these patients, which is considered only when one of the two lesions (AS or AR) becomes severe. Of note, indication for valve intervention in patients with isolated moderate AS is currently under investigation in several randomized clinical trials but only in the presence of relevant symptoms and signs of left ventricular (LV) dysfunction. One initial single-center study including 250 patients with moderate MAVD has evaluated outcomes in this specific subgroup and showed that patients with asymptomatic moderate MAVD and preserved left ventricular ejection fraction (LVEF) had similar adverse event rates (progression to New York Heart Association (NYHA) class III-IV, aortic valve intervention or cardiac death) to patients with isolated asymptomatic severe AS with preserved LVEF. However, the results were primarily driven by the progression of the NYHA Class and aortic valve replacement, and larger multi-center studies are advocated to confirm these findings, which may therefore identify a (new) group of high risk patients who should in principle benefit from an aortic valve intervention as much as patients with isolated severe AS. In addition, prognostic factors (including clinical and echocardiographic characteristics) for risk-stratification of patients with moderate MAVD have not been identified, which may help to refine the indication for valve intervention and optimize patient management.

The endpoint of this study is to develop and validate algorithms, using artificial intelligence and machine learning, to optimize patient selection, treatment planning, treatment evaluation and outcome prediction in patients undergoing thermal ablation of a malignant liver tumor. The long-term objective is to establish thermal ablation as the treatment of choice for the vast majority of patients with a primary or secondary liver tumor by development of an accessible workflow that can be widely implemented in different centers performing thermal ablation. Over a time span of at least four years, data will be collected prospectively, encompassing patient information, tumor characteristics, and treatment details. Additionally, pre-, intra-, and post-procedural imaging will be systematically gathered.

This study will make use of a cross-sectional design of MG patients and non-MG participants to quantitatively assess key MG symptoms, and to explore the applicability of machine learning algorithms to their measurement.

A prospective assessor-blinded randomized clinical trial investigating the effect of aerobic exercise therapy or cognitive behavioural therapy on fatigue in patients with myasthenia gravis.

Rationale: Individuals with advanced age are at a progressively increasing risk of acquiring lower respiratory tract infections. Besides calendar age, the degree of frailty also associates with increased susceptibility to pneumonia requiring hospitalization. How alterations in the mucosal immune system with advanced age predispose to infections remains unclear as access to relevant tissue samples is limited. With minimally-invasive nasal sampling methods, it was recently observed that in vital older adults, both CD4+ T cells and CD8+ T cells are selectively lost from the nasal mucosa. However, the exact phenotype, underlying mechanisms, key molecules and consequences of this have not yet been investigated. Objective: Elucidate the mechanisms underlying the loss of nasal T cells and characterize in depth the differences of T cells in young and older adults and associate this loss with susceptibility to infections. Study design: Prospective cohort study Study population: Participants will be recruited from 3 groups: * healthy young adults (18-30 years, n=50) * vital older adults (\>65 years, n=60) * frail elderly (\>65 years, n=60). This group includes individuals without a history of recurrent respiratory infections or with \>2 self-reported episodes of respiratory infection in the past year. Main study parameters/endpoints: Frequency of nasal CD8+ T cells in young adults and frail older adults. Secondary study parameters/endpoints: * Phenotype (subsets, activation status), functionality, transcriptomic state, clonality and frequency of nasal and blood T cell populations * Stability of T cells and other immune parameters, as described for main study parameter, during a second sample after 3 months. * Analysis of other immune populations as for main study parameter * Concentration of nasal and systemic factors (e.g. cytokines and metabolites) and their association with T cells and other immune populations * Respiratory tract microbiota profiles and presence of asymptomatic viral infections and their association with T cells and other immune parameters * Chronological and biological age, sex, and other immunologically relevant parameters with T cell populations and other immune parameters * Alteration of T cell phenotype, during and following respiratory tract infections. Levels of antigen-specific T cells and other immune parameters in nose and blood post infection.

After hip or knee replacement all patients receive a standardized treatment with blood thinners, this medication is called thrombosis prophylaxis. However, despite this standard treatment some individuals still develop venous thrombosis (VTE), while others experience bleeding. This indicates that not all patients have the same VTE risk following surgery. Individualizing the amount of thrombosis prophylaxis following surgery might lead to less thrombotic and bleeding events. In this study the investigators individualize the treatment with thrombosis prophylaxis based on the medical history of a patient. The main questions this study aims to answer are: Can thrombosis prophylaxis be shortened in patients with a low VTE risk to decrease the risk of bleeding without increasing the risk of VTE? Does an increase in the dose and duration of thrombosis prophylaxis in patients with a high VTE risk reduce the risk of VTE without inducing an unacceptable risk of bleeds? Researchers will compare both the shortened treatment in low VTE risk patients and the intensified and extended treatment in high VTE risk patients with the standard treatment to assess the risk of VTE and bleeding in comparison to the standard treatment. Participants will receive 4 questionnaires to evaluate whether they have experienced a VTE or bleed. For this study no additional hospital visits are necessary.

The goal of this clinical trial is to learn if a new type of scan, FAPI-PET/CT, can help find metastases of gastric cancer. We want to know how well this scan works for this purpose and whether it is less burdensome for patients compared to the methods we currently use to find metastases. The main questions it aims to answer are: * In how many patients can FAPI-PET/CT find metastases, which leads to a change in their treatment plan as decided by their medical team, such as avoiding unnecessary surgeries and changing from treatment meant to cure the disease to treatment focused on comfort (palliative treatment)? * In how many patients does FAPI-PET/CT change the diagnostic process as decided by their medical team, like more biopsies or imaging, or changing the type (extent) of surgery needed? Apart from the usual care gastric cancer patients receive, participants will: * Undergo one additional scan, which will take approximately 2 hours in total (excluding travel time) * Complete a number of questionnaires, which will take approximately 4 hours in total

The goal of this observational study is to comprehensively profile six immune-mediated inflammatory diseases, including atopic dermatitis (AD), plaque psoriasis (PSO), hidradenitis suppurativa (HS), cutaneous T-cell lymphoma subtype mycosis fungoides (MF), chronic spontaneous urticaria (CSU), and cutaneous lupus erythematosus (CLE) in daily practice. Data will be compared with data from healthy volunteers. This study is part of the larger NGID (Next Generation ImmunoDermatology) initiative, of which the main objective is to develop infrastructure that enables personalised patient care. The main questions the SKINERGY study aims to answer are: * Which biomarkers can discriminate between responders and non-responders to treatment in patients with AD, CLE, CSU, HS, MF, and PSO? * How do disease-related biomarkers in patients with AD, CLE, CSU, HS, MF, and PSO differ from those in healthy volunteers? * Which (multi-omics) biomarkers are associated with disease subtypes and predict response or non-response to (targeted) therapies in daily clinical practice? * How do biomarker profiles compare across different cohorts of patients with immune-mediated inflammatory skin diseases (AD, CLE, CSU, HS, MF, PSO) * How do biomarker levels change over time in response to treatment in these patient populations? * Which skin tissue biomarkers are associated with disease progression or treatment response? * How do the genomic profiles of patients differ across diseases or correlate with treatment outcomes? * Can additional imaging biomarkers enhance the characterization of disease profiles or treatment monitoring over time? Researchers will compare both differences beween patients within a disease group in different treatment arms, as well as patients within the same treatment arm. Additionally, biomarker profiles of patients with different diseases will be evaluated. These comparisons will be made to see if shared or distinct biomarker patterns exist across diseases and treatments, which could inform patient stratification, optimize therapeutic decision-making, and identify potential targets for future interventions. Participants will start medication according to national guidelines for the treatment of their inflammatory skin disease (AD: Cyclosporin A, anti-IL4/13, or anti-JAK; PSO: anti-TNF, anti-IL23, ani-IL17, anti-TYK2; HS: anti-TNF, anti-IL17; MF: CHLORM, TSC, PUVA-UV-B; CSU: anti-IgE, Cyclosporin A, anti-BTK\*; CLE: TSC, HCQ, MTX) \*once approved and reimbursed in the Netherlands Participants will: * Take the prescribed medication for their skin disease (in line with standard care in the Netherlands). * Visit the clinic for a study visit combined with their standard care appointment 3 times (baseline, month 3, and month 6. An additional 4th visit at month 12 is optional). * Fill in an online set of questionnaires from home, 3 times during the study period (an additional 4th time is optional). * Patients with CSU fill in the UAS7 (and if applicable the AAS7) daily for the study period.

Accurate assessment of skin pigmentation is essential in dermatology for properly diagnosing and managing a wide range of skin conditions. Traditionally, skin colour has been evaluated through visual inspection or by using classifications like the Fitzpatrick skin type. However, these methods can be subjective, culturally biased, and often are centered around lighter skin tones, which may lead to misdiagnosis or inappropriate treatment for individuals with darker skin. With advances in technology, non-invasive imaging tools such as colorimetry and multispectral imaging now offer more precise and objective ways to measure skin pigmentation. These methods can help provide consistent and unbiased information about skin tone, benefiting both clinical care and research. Despite these technological advances, there is currently no agreed-upon standard for how to measure skin pigmentation objectively in everyday clinical practice or research settings. This study aims to explore better, more accurate ways to measure skin pigmentation using modern, non-invasive imaging technologies. Traditional methods for assessing skin colour, like visual inspection or classifying by ethnicity, are often unreliable and biased. In this study, researchers will use tools such as colorimetry and multispectral imaging to measure skin pigmentation more objectively. The study includes two groups of participants: healthy adults and adults with skin conditions. Researchers will measure a value called the melanin index, which reflects the amount of pigment in the skin, and compare it across different areas of the body and among people with different skin tones and conditions. The goal is to understand how skin pigmentation varies and to see if these new technologies can help doctors more accurately diagnose and manage skin diseases for people of all skin types.

This is a Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial evaluating the safety and efficacy of once-weekly semaglutide 2.4 mg in adult patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) who meet current clinical criteria for semaglutide treatment. A total of 826 participants will be randomized 1:1 to receive semaglutide or placebo as an add-on to standard-of-care, starting 3 months before TAVR and continuing for 24 months post-procedure. The primary endpoint is time to first occurrence of a composite of cardiovascular (CV) death, non-fatal myocardial infarction, non-fatal stroke or transient ischemic accident (TIA), and hospitalization for heart failure (HF). The study is event-driven and powered to detect a 20% relative risk reduction in primary outcome events. This trial aims to address the unmet need for medical therapies that improve outcomes in patients with severe AS following TAVR, with potential for direct clinical implementation.