P, Czech Republic

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

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.

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.

Rocket Study: A Study to Characterize Biomarkers and Disease Progression in Participants With Pelizaeus-Merzbacher Disease

This is a multi-center, non-randomized, non-interventional integrated prospective and retrospective study in up to 32 participants with PMD who can undergo general anesthesia or conscious sedation (if necessary) to collect fluid biomarkers (CSF and blood), neuroimaging, and clinical assessments to be used in support of the development of therapies for PMD. The study duration for each participant will be approximately 26 months (Week 106).

Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare

This is a multi-center Phase 2/3 randomized, double-blind, placebo-controlled, parallel-group safety and efficacy study of dapansutrile (OLT1177®), a specific NLRP3 inhibitor, conducted in subjects with acute gout flare. Up to 300 eligible subjects will be randomized 2:1 to one of two treatment arms to receive either dapansutrile tablets or matching placebo twice daily for 7 days. An initial loading dose on Study Day 1 will be followed by a twice daily maintenance dosing regimen. Subjects presenting with acute gout flare that began within 96 hours prior to the Screening/Baseline/Day 1 visit will be evaluated for eligibility. Subjects who are determined to be eligible will be randomized into either an active treatment arm (2/3 of the subjects enrolled) or the placebo arm (1/3 of the subjects enrolled). Eligible subjects who are randomized into the study will also be provided with rescue medication at the Baseline/Day 1 Visit. No other pain medications, anti-inflammatory drugs (e.g., steroids or nonsteroidal anti-inflammatory drugs), or treatments for gout flare are allowed during the Treatment Period. During the Treatment Period, subjects will return to the clinic trial site on Day 4 and, following the 7-day Treatment Period, subjects will return to the clinical trial site on Day 8, and then Day 15 with safety data collected through Day 36.

MAD Trial: Myopia Atropine Dose

With the current worldwide myopia boom the frequency of high myopia will also increase, and potentially blinding complications such as myopic macular degeneration, retinal detachment, and glaucoma will occur more often. In the Netherlands high myopia will become the most important cause of low vision and blindness by 2050. As treatment options are limited once the eye is fully grown, prevention of a long axial length at childhood is the only way to counteract this prospect. Pharmacological interventions have shown a high efficacy in stopping eye growth, in particular eye drops with high dose Atropine (0.5%, 1%). Nevertheless, the high frequency of side effects (photophobia, reading problems) of these Atropine concentrations has favoured the use of low dose Atropine. Atropine 0.01% is the most commonly used and lowest dosage; it has shown stability of refractive error, but not of axial length. Recent studies have shown that Atropine 0.05% has low risk of side effects, but a higher efficacy than 0.01%. Many ongoing trials are now comparing various low dose Atropine to placebo, but none are comparing the highest low dose to the lowest high dose Atropine.

A Study of JNJ-79635322 in Participants With Relapsed or Refractory Multiple Myeloma or Previously Treated Amyloid Light-chain (AL) Amyloidosis

Effect of Functional Power Training on Calf Muscle Length and Strength in Children With Spastic Paresis

Flexion-Extension Radiograph Imaging Protocol Reliability Study

Lumbar spinal stenosis, a narrowing of the spinal canal in the lower part of the back, is a relatively common medical problem, but optimal treatment for the condition is poorly understood. Lumbar spinal stenosis is commonly treated with decompression surgery (providing more space for the compressed nerve roots) with or without additional lumbar fusion surgery (connecting two or more vertebrae to eliminate instability). Orthopaedic surgeons are currently faced with the dilemma of whether or not to add fusion to a decompression procedure. To decide between these two surgical options, surgeons rely mostly on their personal experience. They have to subjectively gauge whether a level is unstable preoperatively or if a specific decompression procedure is likely to destabilize the spine. A valid and reliable test for spinal instability would facilitate research to determine whether spinal instability measurements can be used to choose the optimal surgical treatment for each level. A reliable diagnostic assessment for spinal instability would ideally be validated using an existing "gold standard" test. Such a test should have a very high sensitivity and specificity and must be supported by clearly developed rationale and high-quality evidence. Unfortunately, such a test does not currently exist for spinal instability. However, abnormalities in intervertebral motion are often a hallmark for spinal instability. A commonly accepted way to examine intervertebral motion is by analyzing the patient's flexion-extension radiographs. Using these two radiographs, the spine's sagittal plane intervertebral motion can be measured. The relative motion between the two images can be measured at all relevant levels either through manual measurement or computer assisted methods. Ideally, a standardized flexion-extension radiograph imaging protocol accomplishes the following: the patient sufficiently stresses the spine in order to assess the integrity of intervertebral motion restraints (ligaments, annulus, facet capsule, etc.), it is easily implemented into the clinical work flow, and it is reliable and repeatable across subjects and clinicians. A myriad of patient positioning protocols for the flexion-extension radiograph imaging procedure have been tested and deployed, although generally without well-validated success criteria. Despite the large amount of studies on the topic, no one flexion-extension radiograph imaging protocol has been widely accepted. This suggests that 1) the studies were not appropriately powered to influence change, 2) some protocols (methods, equipment, instructions, etc.) are not easily implemented or practical in routine clinical workflows, 3) acquiring radiograph images of the lumbar spine in sufficiently stressed positions is not widely accepted as clinically important, or 4) most ordering clinicians do not realize how often a patient fails to adequately stress the spine while undergoing a standard of care flexion-extension radiograph. One factor that can often cast doubt on the efficacy of the flexion-extension radiograph procedure is the level of patient effort or range of spinal motion achieved by the patient. For standing flexion-extension radiographs, more patient effort leads to more intervertebral motion. This is a fairly simple and intuitive concept. However, achieving maximum patient effort is not a simple task. It could be argued that symptomatic patients should not be expected to exert maximum effort because it can be painful or uncomfortable. This argument can be supplemented with evidence that fear avoidance can limit motion and intervertertebral motion is substantially increased after analgesic injections. Despite some of the arguments that can be used against the implementation of standardized flexion-extension radiograph imaging protocols in assessing spinal instability, there is ample data that good patient effort can be obtained in symptomatic patients. In one large multi-site study of lumbar stenosis with the exact same patient inclusion/exclusion criteria, a large amount of variance can be seen in the average level of intervertebral rotation. This suggests that differences in the flexion-extension radiograph protocol could be the driving factor in this high amount of variance seen between sites. It is also possible that the physician and/or radiology technician helped to quell patient's fear of motion by explaining that the maximum flexion and extension will not injure their back and will provide the best data for a reliable diagnosis. With this in mind, the need for a standardized flexion-extension radiograph imaging protocol to assess for spinal instability is evident. Such standardized protocols can influence the amount of intervertebral motion, both translational and rotational. Since intervertebral motion is often used as evidence for spinal instability, inadequate effort likely leads to false negatives for spinal instability. Thus, developing a standardized imaging protocol to reliably measure intervertebral motion during a flexion-extension exam is clinically significant, as it often influences the diagnosis of a patient.

A Study of NVL-520 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1)

In Phase 2, study patients will be enrolled into 5 distinct expansion cohorts: - Cohort 2a: ROS1-positive NSCLC naïve to Tyrosine Kinase Inhibitor (TKI) therapy and up to 1 prior chemotherapy and/or immunotherapy. - Cohort 2b: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy. - Cohort 2c: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy. - Cohort 2d: ROS1-positive NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy. - Cohort 2e: ROS1-positive solid tumor and progressed on any prior therapy.