Hx Maastricht, Netherlands

The TearAD Study: Tear Biomarkers for Alzheimer's Disease (AD) Screening and Diagnosis

The Role of the Tumor Molecular Profile (CMS), UGT1A1 Genotype and Beta-glucuronidase Activity of the Intestinal Microbiota for Treatment Efficiency, Toxicity, Survival and Quality of Life in Patients With Metastatic or Unresectable Colorectal Cancer During Irinotecan-based Systemic Treatment

Irinotecan-based systemic therapy is shown to have promising results in metastatic or unresectable colorectal cancer. However, this therapy has two major disadvantages, including an unpredictable individual treatment response and late-onset systemic and gastrointestinal toxicity. To target these problems, biomarkers are needed which could be used to predict treatment response and toxicity before start of the treatment. The molecular profile of the tumor (consensus molecular subtypes (CMS)), the UGT1A1 genotype and the gut microbiota-derived enzyme β-glucuronidase are promising candidates in this context. Recent research demonstrated that irinotecan-based systemic therapy increased both progression free survival (PFS) and optimal survival (OS) predominantly in patients with CMS4 cancers, as well as in preclinical models representing this subtype. For the other CMS subtypes (CMS1-3), irinotecan-based systemic therapy was shown to be significantly less efficient. For the UGT1A1 genotypes, decreased activity of the UGT1A1 enzyme (converting the toxic metabolite SN-38 into the inactive SN-38G) will increase the concentration of toxic SN-38, resulting in systemic toxicity. Lastly, the importance of studying bacterial β-glucuronidase (β-GUS) activity in CRC patients during treatment with irinotecan can be derived from recent animal studies, and indirect human evidence. Previous research has shown that high bacterial β-GUS activity (converting the inactive SN-38G into the toxic SN-38) might be a possible indicator for irinotecan-induced late-onset gastrointestinal toxicity due to SN-38 accumulation. Therefore, the OPTIMA study was developed to combine prediction of tumor sensitivity towards irinotecan (by CMS classification), UGT1A1 expression for irinotecan dose determination, and β-GUS for risk assessment for late-onset gastrointestinal toxicity. The aim of the study is to investigate whether the molecular profile of the tumor (e.g. based on CMS), the UGT1A1 genotype and β-GUS activity can act as a predictor for therapy efficiency, late-onset systemic and gastrointestinal toxicity, as well as OS and quality of life (QoL).

Clinical Study Evaluating Pharmacogenomics-informed Pharmacotherapy Versus Dosing As Usual in Psychiatric Disorders

Effective pharmacotherapeutic treatments for mental disorders are available, but their effectiveness is limited by low compliance due to frequent side effects. This is partly due to patient heterogeneity in the genes encoding for drug-metabolising enzymes. Pharmacogenetic testing allows the assessment of person-specific genetic factors that are thought to predict clinical response and side effects. Recent studies have suggested that genotyping genes encoding drug-metabolizing enzymes may improve treatment efficacy and tolerability, potentially benefitting millions of patients. PSY-PGx is the first initiative to propose a large-scale non-industry sponsored clinical study that aims to demonstrate the clinical benefits and potential of the implementation of pharmacogenetics for psychiatric patients in existing medical settings. This is an international 24-week, patient- and rater-blinded, two-arm, parallel-group controlled, and multi-centre randomized clinical trial (RCT) to establish the benefits of pharmacogenetics-informed pharmacotherapy versus dosing as usual (DAU) in psychiatric patients suffering from mood, anxiety, or psychotic disorders.

Evaluation of the Use of the FUR to Quantify Tumor Glucose Consumption in Oncologic PET

As most tumours have a high glucose consumption, important information on tumour metabolism can be obtained from PET imaging using 18F-FDG as a radioactive glucose analogue. From literature it is known that quantitative analysis improves the clinical value of 18F-FDG PET. However, instead of measuring the true tumour glucose consumption Km, in current clinical practice the 18F-FDG uptake is measured at a certain time after administration as a surrogate for Km, the so-called standardized uptake value (SUV). As the SUV suffers from a number of important shortcomings, discrepancies between Km and the SUV have been reported which may lead to erroneous conclusions regarding disease progression based on the SUV. Alternatively, pharmacokinetic modelling approaches facilitate accurate Km assessment. Unfortunately, these approaches typically require complex mathematical modelling, lengthy dynamic PET imaging and/or invasive arterial blood sampling and are therefore not compatible to current clinical oncologic 18F-FDG PET scanning. However, from these models it can be derived that at late time points after administration Km can be approximated using a simplified approach known as the fractional uptake rate (FUR). Our hypothesis is that the correlation between the FUR and Km is superior compared to the correlation between the SUV and Km. Therefore we expect that quantification of 18F-FDG PET images based on the FUR is superior to SUV quantifications. The results of this study may therefore lead to a new and improved method to quantify oncologic PET images which may enhance the diagnostic value of PET. In particular, this method may lead to a more accurate assessment of tumour response to therapy and may therefore prevent continuation of unsuccessful therapy or termination of a successful therapy. Primary objective: To investigate whether the correlation between the FUR and Km is superior compared to the correlation between the SUV and Km. Secondary objectives: 1. Validation of the FUR in 18F-FDG PET to accurately assess tumour metabolic activity Km. 2. To investigate the impact of the use of patient-specific versus a (scaled) population-based input function on the accuracy of Km assessment using the FUR. The risks and patient discomfort associated with this scientific study are low. Only patients are included who already receive an 18F-FDG PET/CT scan as part of standard care. Instead of resting on a standard hospital bed for one hour after 18F-FDG injection, patients will be resting inside the PET/CT system while a dynamic PET acquisition is performed. In addition to their standard PET/CT examination, an extra low-dose attenuation CT scan will be performed resulting in an added radiation exposure of the patient of 3.6 mSv. Moreover, three additional venous blood samples will be obtained at three time points, one before and two after 18F-FDG administration will be obtained from the patient.

REsponsible roLl-out of E-heAlth Through Systematic Evaluation - Heart Failure Study

The objectives of the study are to examine: 1. which HF patient characteristics are related to an increase in number of days spent outside the hospital within one year of follow-up, when telemedicine is part of regular HF care compared to regular HF care alone? 2. which HF patient characteristics are related to cost-effectiveness when telemedicine is part of regular care compared to regular HF care alone? 3. which components of telemedicine as part of regular HF care lead to an increase in number of days spent outside the hospital within one year of follow-up? 4. which components of telemedicine as part of regular HF care are cost-effective? The main focus of this study is on patient-related subgroup analyses with telemedicine. The patient-related subgroups are identified by a systematic literature review of randomized-controlled trials of telemedicine: (1) age, (2) severity of HF (NYHA class at baseline), (3) sex (female compared to male), (4) socio-economic status (SES) (HF patients with higher SES compared to lower SES), (5) presence of depression, (6) Type of heart failure (LVEF: HFrEF, HFmrEF, HFpEF), (7) presence of atrial fibrillation (AF). In an additional analysis, (8) heterogeneity across time of diagnosis will be explored (recently diagnosed compared to not recently diagnosed). To answer the four research questions a RELEASE-HF database will be set up. The RELEASE-HF database will be composed from various data sources: 1. National Heart Failure Registry (abbreviated as Registry; a patient registry), 2. Interviews with clinicians about telemedicine features on hospital level, 3. Interviews with finance department staff about costs in HF care (including telemedicine use), 4. Electronic Health Record (EHR) data about telemedicine (including supplier system data) 5. External national registries and/or databases as Statistics Netherlands (CBS), declaration data (Vektis), Dutch Hospital Data (DHD) or PHARMO.

The Effect of LSD on Neural Synchrony, Prosocial Behavior, and Relationship Quality

Evidence is growing that psychedelic substances such as psilocybin, lysergic acid diethylamide (LSD) and ayahuasca could be a potential alternative treatment option for common and difficult to treat psychiatric conditions. One proposed mechanism that psychedelics target, which is a hallmark of seemingly all psychiatric disorders, are deficits in social cognitive abilities. However, the neural underpinnings of psychedelic induced alterations in prosocial behavior are currently unknown. The investigators hypothesize psychedelics increase such prosocial behaviors by increasing neural synchrony, which is the coupling of brain-to-brain activity across two or more people; it has been found to underlie social connection and various forms of shared prosocial behavior. The current project will primarily assess whether LSD enhances neural synchrony between romantic partners. Second, the investigators will assess whether LSD enhances prosocial behavior between members of a dyad, thus replicating previous studies which assessed prosocial behavior within one individual at a time. The investigators will also assess the relationship between neural synchrony and outcome variables of the prosocial behaviour tasks. Lastly, it will be assessed whether LSD-induced changes in neural synchrony and/or prosocial behaviour affect persisting relationship quality. Oxytocin and cytokine concentrations, will also be quantified to investigate whether there is a relationship between these factors and changes in prosocial behaviour. The study design will be conducted according to a double-blind, placebo-controlled, 2-way crossover design. Healthy participants (N=60) who are in a relationship (N=30 couples) will receive placebo and an oral dose of 50 µg of LSD. Between each condition, there will be a minimum of 14 days washout. This leads to a total study duration of minimally four weeks, for a participant to go through the medical examination and both drug conditions.

A Study of DZD9008 Versus Platinum-Based Doublet Chemotherapy in Local Advanced or Metastatic Non-small Cell Lung Cancer (WU-KONG28)

Anabolic Properties of Canola

Screening and pre-testing To assess whether volunteers are eligible to participate in this study, we will invite them to the University for a screening. At the start of the screening session, the entire experimental trial will be explained and any potential questions will be answered. Thereafter, the volunteers are asked to read, fill out, and sign the informed consent form. After signing the informed consent form, the participant's eligibility will be assessed based on the in- and exclusion criteria. To further assess their eligibility, participants will be asked to fill out a medical questionnaire to assess their general health, use of medication, habitual food intake, and physical activity (Appendix F1.1). Next, blood pressure will be assessed. Body mass (with accuracy of 0.1 kg) and height (with accuracy of 0.01 m) will be determined, and body composition will be assessed via a Dual Energy X-ray Absorptiometry (DEXA) scan. A DEXA scan is a simple, non-invasive procedure. At the beginning of the procedure, subjects will be asked to lie down on a scanning table wearing underwear and they need to remain motionless during the measurements. As the scanner moves, a dual energy beam passes through the targeted skeletal muscle section and is measured by a detector. This procedure is repeated until the whole body is scanned and takes approximately 3 minutes. The screening sessions will take place in the morning and participants are instructed to not have any breakfast in the morning in order to avoid perturbations in the DEXA scan. In the event of an unexpected medical finding during the screening, subjects will always be notified. If a subject does not want to receive this notification, she cannot participate in the study. Next, subjects will be familiarized and tested for bilateral strength on the exercise machines. First, participants will warm up on a cycle ergometer for 5 minutes at 100W. Subjects will be instructed on proper weight-lifting technique on each exercise machine (leg-press and leg-extension) and complete a standardized testing protocol to determine a measurement of maximal strength (1RM) for each exercise machine. In short, subjects will be seated on a leg press and leg extension machine and start with a warm-up of 2 sets of 10 repetitions with self-chosen weights. Then the load will be increased above the warming-up weight. The load will be increased after each successful lift, until failure, to determine maximal strength. A repetition is classified as "valid" if the participant is able to complete the entire lift in a controlled manner, without assistance. When the screening is successfully performed, the test day will be scheduled. In order to prevent major impact from the menstrual cycle on the measurements of protein metabolism, the test day will be scheduled to take place in the first 10 days of the follicular phase. Each subject will participate in an experimental trial lasting ~9h. Subjects will be instructed to arrive at the university at 7:45 AM in an overnight fasted and rested state, meaning that participants are not allowed to eat and drink (except for water) from 22:00 the night prior to the experimental trial. They will be instructed to come to the university by car or public transportation. After the subjects arrive at the University, we will ask them to put on their shorts, determine their body mass, and assign them to a bed. Subjects will rest in a supine position and a Teflon catheter will be inserted in a heated dorsal hand vein and placed in a hot-box (60°C) for arterialized blood sampling. A baseline blood sample (Serum + plasma = 20 mL) will be collected at t= -210min to determine the amino acid enrichment level prior to the intervention. Following basal blood sample collection, a second Teflon catheter will be inserted into an antecubital vein of the contralateral arm for stable isotope infusion with the amino acids 13C6-phenylalanine and 2H2-tyrosine. At the start of the isotope infusion, the plasma phenylalanine and tyrosine pools will be primed with a single dose of the tracer solution, directly thereafter the continuous tracer infusion will commence. During the entire experimental test day, the hand with the dorsal hand catheter will be pre-heated for 10 minutes prior to every blood draw in a hot box at 60°C to increase blood flow. This makes it easier to collect blood and minimizes nutrient exchange from blood into other tissues. Therefore, it allows us to collect nutrient-rich (arterialized) blood from a vein. Arterialized blood samples (10mL) will be collected at t = -180, -120, -60, and 0 min to assess plasma tracer enrichments during the tracer infusion in the resting overnight post-absorptive period. After a pre-infusion period of 30 minutes (t = -180), during which the tracer infusion reaches steady state, a first muscle biopsy will be taken from the m. vastus lateralis to determine the background enrichment. At t=-45 min, a resistance-type exercise session will be performed (40 minutes). Subsequently, at t= 0 min a second biopsy will be taken from the same leg in order to assess the basal muscle protein synthetic rate. Immediately after the second biopsy, subjects will ingest the assigned drink (20g canola or whey protein or a non-caloric placebo). Subjects will be instructed to consume the drink within ~5 min. Upon drink ingestion, the stopwatch will be reset (t= 0 min), and arterialized blood samples (10 mL) will be collected at t = 30, 60, 90, 120, 180, 240, and 300 min during the post-prandial period to assess plasma amino acid profiles and enrichments. To determine postprandial muscle protein synthesis (MPS), another biopsy will be taken at t = 300 min following meal ingestion from the contra-lateral leg. The muscle biopsy at t = 300 min allows us to obtain physiological relevant information with regard to the duration of the anabolic response to protein intake over a commonly used 5h postprandial period. Collectively, with the obtained biopsies we can measure muscle protein synthesis in the resting state (-180 - 0 min) and entire postprandial period (0 - 300 min; main outcome). During the test day, a total of 3 muscle biopsies will be taken through 3 separate incisions, 2 biopsies from the one leg and 1 biopsy from the other leg. In total 12 times blood samples will be taken during the test day, the first sample that will be collected will be 20mL the subsequent samples 10mL, for a total of 130mL. Additionally, gastro-intestinal (GI) symptoms will be assessed at t = -60, 30, and 180 minutes and palatability at t = 15 min by questionnaires

Viamigo for People With Dementia and Their Informal Caregivers

Rationale: People with dementia living in the community experience reduced out-of-home mobility and participate less in activities outside the home. This results in reduced social participation outside the home, which can negatively affect their health (e.g. leads to social isolation and increased risk of depressive symptoms). Technological interventions show promise in enhancing the social participation of people with dementia. However, there is a lack of technological interventions that facilitate social participation outside the home. While a growing body of evidence highlights the potential of Geographic Information Systems (GIS) in facilitating the out-of-home mobility of people with dementia and reducing informal caregivers' feelings of worry, very little attention is paid to the potential of GIS in enhancing the social participation of people with dementia. The GIS-based mobile application Viamigo aims to support the independent out-of-home mobility of the user and to reduce informal caregiver's burden by teaching users a known individual route, which they can accomplish independently afterwards while being monitored by an informal caregiver. Although Viamigo was initially developed for persons with intellectual disabilities, it is expected that it can also support and improve out-of-home mobility and thereby the social participation of people with dementia. Objective: The main objective of this study is to evaluate the feasibility of the Viamigo intervention among people with dementia living in the community and their informal caregivers. The secondary objective of this study is to assess the first responses of people with dementia and informal caregivers to the Viamigo intervention. Study design: This feasibility study includes a mixed methods single-arm pre-post design with a baseline assessment, a 3-month intervention period, and a post-intervention assessment. Study population: The study population consists of dyads (n=24) of people with mild to moderate dementia living in the community and their informal caregivers. There are no restrictions regarding sex, educational level, or cultural background. Intervention (if applicable): All eligible and consenting dyads will be asked to participate in the Viamigo intervention, consisting of three main components: (1) a face-to-face technology training session of 60 minutes, (2) a 3-month period of using the Viamigo intervention with support phone calls of approximately 5 minutes by the coordinating investigator once every two weeks, and (3) an evaluation phone call of 5-10 minutes. Main study parameters/endpoints: The main study parameter is the feasibility of the Viamigo intervention for people with dementia and their informal caregivers. Secondary study parameters for people with dementia include out-of-home mobility and social participation. Secondary study parameters for informal caregivers include quality of life, caregiver burden, and gains in dementia caregiving. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: People with dementia will be asked to fill in the same two questionnaires (approximately 20 minutes in total) during the baseline and post-intervention assessment. Additionally, they are asked to fill in a daily travel diary for one week at baseline and during the last week of the intervention period. Informal caregivers will be asked to fill in the same three questionnaires (approximately 25 minutes in total) during the baseline and post-intervention assessment, and another 15-minutes questionnaire during the post-intervention assessment. Additionally, a smaller sample of the dyads (10 dyads) will be asked to share their experiences using the Viamigo intervention in a semi-structured post-intervention interview of approximately 30 minutes. Dyads will be asked whether they prefer to conduct the different assessments at home or at another location (e.g. Maastricht University). By participating in the study, a participant with dementia might be more often exposed to potentially risky situations in his or her living environment (e.g. traffic). Participation in a technological intervention study can be time-consuming and demanding. One way to reduce the burden of the study is to give participants the freedom to use the Viamigo application at their own pace.