Wilhelmsfeld, Germany

Adjusted High-dose Chemotherapy with Autologous Stem Cell Transplant Vs. Conventional Immunochemotherapy in Elderly PCNSL Patients

Primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is a rare lymphoma affecting only the central nervous system compartment. PCNSL patients are typically 60 years or older and have poor prognoses. However, there are alternative treatment approaches to consider with the potential to improve medical outcomes for this patient population. The current standard of care in Germany and many international centres for patients 65 and older is treatment with R-MP, comprising rituximab, high-dose methotrexate (HD-MTX) and procarbazine followed by maintenance therapy with procarbazine. An alternative approach comprised of a shorter induction treatment with rituximab, HD-MTX and cytarabine (MARTA) followed by age-adjusted high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) was recently shown to be feasible and effective in elderly PCNSL patients considered eligible for high-dose chemotherapy requiring autologous stem cell transplantation. Nevertheless, data evaluating this short duration treatment approach remains scarce, and randomized trials have not yet been published. The objective of the PRIMA-CNS trial is to demonstrate that intensified chemotherapy followed by consolidating HCT-ASCT is superior to conventional chemotherapy with R-MP followed by maintenance with procarbazine in elderly patients with newly diagnosed PCNSL; not only regarding survival and remission after treatment but also regarding standards like quality of life (QOL) and treatment related morbidities. Results of this randomized trial will either change the standard of care to an intense and shorter treatment approach or re-define R-MP as a proven treatment standard. In addition, a geriatric assessement is implemented in this trial with the goal to better define transplant eligibility. If this trial shows the superiority of HCT-ASCT, the investigators will establish an improved treatment standard with increased chances for long-term remission and cure and reduced frequency and length of chemotherapy treatment. Considering the poor prognosis of this patient population, this randomized phase III trial is of great clinical importance to provide patients, the patients' families and care takers with optimal treatment.

A Non-interventional Study Evaluating Clinical Utility and Implications on Improved Patient Management of Serum Neurofilament as a Prognostic Marker for Disease Activity in Patients With Relapsing Multiple Sclerosis

Prospective, primary data will be collected from patients with sNfL outcomes in the context of switching to ofatumumab or continuing their current therapy. Data collection will cover a maximum period of 24 months. The observational period will not be dictated by the protocol. Baseline and follow-up visits will take place at a frequency defined as per Investigator´s discretion following clinical routine. The diagnostic or monitoring procedures are only those ordinarily applied to therapeutic strategy and routine clinical care. During the observation phase of the study, data will be collected according to standard of care as recommended by KKNMS (Competence Network Multiple Sclerosis in Germany). Eligible participants for the study are patients who have received treatment with category 1 DMTs and those who have included sNfL into their treatment decision-making process. These patients have the option to either continue their current DMT or switch to ofatumumab. According to local treatment guidelines, DMT category 1 include dimethylfumarate/diroximelfumarate, glatirameroids, Interferon beta and teriflunomide. The decision to switch to ofatumumab or to continue the current DMT category 1 therapy must be made by the treating physician independently of the decision to enroll the patient in the study.

Attexis and tDCS for the Treatment of ADHD

The aim of this study is to determine whether the effectiveness of the home-based therapy program "Attexis" can be augmented with another home-based procedure, tDCS treatment, in order to achieve even higher improvement rates in the treatment of ADHD in the future. Before the actual start of treatment with Attexis, the presence of an ADHD diagnosis (ICD-10: F90.0) is checked by qualified medical staff at Medbo Regensburg. If the screened patient then meets the other inclusion criteria for Attexis and tDCS, he or she will be randomly assigned to either the intervention group (receives access to both Attexis and tDCS) or the placebo group (receives access to both Attexis and placebo tDCS). Based on the study by Schlechter et al. (2023), it is planned to treat patients receiving (placebo) tDCS treatment with 60 sessions (2mA, 20 minutes per day) by stimulating the left DLPFC. As patients will have a three-month access to Attexis, it is planned to administer the additional (placebo) tDCS treatment at the same time. As soon as a patient registers for the study, the safety aspects and inclusion/exclusion criteria for tDCS treatment are also checked in an initial interview after the ADHD diagnosis has been verified. The patient is then randomly assigned to one of the two study arms. A suitable appointment is then arranged for the patient to be admitted to the device. About 60 minutes are scheduled for the explanation and instruction of the tDCS device. During the appointment, an initial trial treatment is carried out so that the patient can get used to the treatment. All subsequent home-based treatments are carried out from Monday to Friday (each lasting 20 minutes) with video observation during the first week of treatment. For the sessions via teletherapy, software approved for clinical use (CLICKDOC version 5.9.1, La-Well Systems GmbH, CompuGroup Medical SE & Co. KGaA, Bünde, Germany) is to be used. At the end of the tDCS treatment, a final consultation will be arranged, which will take about 45 minutes. A follow-up (clinical ratings and attention test) will be carried out after 3 months.

Bemarituzumab in FGFR2b+ Patients with Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction, Who Failed At Least One Prior Line of Palliative Chemotherapy

TIDE Project: Biomarker Discovery for Chronic Tinnitus Diagnosis

The tinnitus detect (TIDE) consortium has been designed to identify and validate a biomarker for the presence and intensity of tinnitus. For this purpose, two test paradigms are combined which are derived from the most recent models of tinnitus and which have shown promise in pilot studies. A first approach is based on a method used in animals to objectively assess tinnitus by gap detection, namely Gap prepulse inhibition of the acoustic startle (GPIAS). The GPIAS paradigm is inspired from the combination of both gap detection and pre-pulse inhibition (PPI), used for the assessment of temporal sensory processing in both animals and humans. The basic principle of PPI relies on the ability of a weak lead stimulus (a prepulse or a silent gap presented in a carrier background) to inhibit a startling effect of a following, more intense, abrupt stimulus. These paradigms have been used to assess the automatic or preconscious inhibition of the motor reflex response that occurs in healthy subjects. Because GPIAS is regulated at the level of the auditory cortex, cortical responses may provide a more accurate measure of inhibition than motor reflex responses, such as the startle response in animals or the eye blinking in humans. The hypothesis is that individuals with tinnitus would have impaired inhibition of cortical evoked responses to sound pulses when preceded by a silent gap, in comparison to non-tinnitus individuals, due to the ongoing tinnitus percept. A second approach is based on the concept that tinnitus occurrence is related to altered processing of prediction errors. This concept is supported by empirical evidence demonstrating that people with tinnitus exhibit a more pronounced electrophysiological response to a mismatch between predictions (the expected sound based on the auditory training paradigm) and perceptions as compared to non-tinnitus individuals. This sensitivity to prediction errors (the difference between prediction and input) is associated with how loud patients perceive their tinnitus, independent of co-occurring hyperacusis and hearing loss. For example, the amplitude of the mismatch negativity (MMN) positively correlates with subjectively reported tinnitus loudness. Thus, the MMN might be a biomarker for how loud tinnitus patients perceive their tinnitus. That is, people with a more pronounced electrophysiological response to a prediction error perceive a louder phantom sound. Using another paradigm, a group, independent of us, confirmed the importance of the MMN for tinnitus detection. Furthermore, an increase in amplitude and a delay in latency for the late positive evoked brain response (P300) has been demonstrated in tinnitus patients using both auditory and visual oddball paradigms. Both the MMN and P300 are conceived as measures of prediction errors identified at respectively the sensory cortex and higher levels (i.e., frontal-parietal cortex). The P300 is thought to reflect processes involved in stimulus evaluation or categorization; whether the stimulus is behaviourally relevant or not. Therefore, the aim of the current approach is to validate that both the MMN and the P300, using an auditory oddball paradigm with omission, can be used as biomarkers for tinnitus loudness and presence, respectively, (i.e., cross-validation). We propose to investigate these two paradigms in a large international sample of tinnitus patients and controls in order to determine the sensitivity of GPIAS and the oddball paradigm in diagnosing tinnitus in humans.

Real-world Experience With Lutetium Vipivotide Tetraxetan in Metastatic Castration Resistant Prostate Cancer

This non-interventional observational, prospective cohort study is using primary data collection to describe the routine clinical practice and HRQoL of patients with Metastatic castration-resistant prostate cancer (mCRPC) initiating lutetium (177Lu) vipivotide tetraxetan using patient questionnaires. Data will be collected at the following time points: pre-index (if patient is eligible), index date (first application of lutetium (177Lu) vipivotide tetraxetan), during treatment, at EoT, and during follow-up. The duration of a treatment cycle is 6 weeks (± 1 week). Patients will be treated for up to 6 cycles (as per local label). EoT visit / assessments will be performed after the last lutetium (177Lu) vipivotide tetraxetan application. Follow-up period: patient data will be collected if available up to 1 year after EoT.

Neurofilament Light Chain in Amyotrophic Lateral Sclerosis

The aim of this study is to investigate the correlation between the NfL serum concentration and the natural course of the disease, the ALS progression rate as measured by the ALS functional rating scale (ALSFRS-R), and specific phenotypes of ALS. The results of the study will contribute to the assessment of disease progression and the prognosis making of ALS. Furthermore, the performance of NfL as a therapeutic marker of ALS medicines and non-pharmacologic treatment options will be investigated. A systematic analysis of the NfL serum concentration in an extended cohort of ALS patients using the Single Molecule Analysis method (SIMOA) will be performed. Research objectives comprise: - Correlation of NfL with disease progression, including duration of ALS disease - Correlation of NfL with the course of ALS (classic ALS or variants in the motor neuron involvement or the regional propagation patterns) - Correlation of NfL with the progression rate of ALS Cohorts on phenotypic variants: The clinical phenotype of ALS will be differentiated according to the motor neuron involvement or regional propagation patterns of disease onset and clinical course. ALS variants in relation to motor neuron involvement: - Typical ALS: clinical features for an affection of the 1st and 2nd motor neurons are present - Progressive muscular atrophy (PMA): only clinical features for an affection of the 2nd motor neuron are present - Spastic ALS: predominantly clinical features for an affection of the 1st motor neuron and fewer signs of an affection of the 2nd motor neuron - Primary lateral sclerosis (PLS): only clinical features for an affection of the 1st motor neuron are present ALS variants in regional propagation patterns: - Typical form: paresis of the upper or lower extremities or the bulbar region as well as the spread of the paresis to other regions - Flail arm syndrome: primary and dominant paresis of the upper extremities and little or delayed spread of the paresis to other regions - Flail leg syndrome: primary and dominant paresis of the lower extremities and little or delayed spread of the paresis to other regions - Axial ALS: primary and dominant paresis of the trunk muscles and minor or delayed spread of the paresis to other regions - Progressive bulbar paralysis: primary and dominant paresis in the bulbar region and slight or delayed spread of the paresis to other regions

A Study to Investigate LDL-cholesterol Lowering With Inclisiran Compared to Bempedoic Acid in Patients With Atherosclerotic Cardiovascular Disease.

During the screening period study eligibility will be assessed and the participants' individual LDL-C target according to guideline (Mach et al., 2020) will be determined. Among other criteria, at screening, a participant must be on a stable maximally tolerated dose of a HI statin with either atorvastatin ≥40 mg once a day (QD) or rosuvastatin ≥20 mg QD (+/- Ezetimibe [10mg]) for ≥ 4 weeks with which, however, a target LDL-C of < 70 mg/dL is not reached. During the open-label treatment period, all participants, who fulfill the inclusion/exclusion criteria, will be randomized at V1 (Day 1) in a 1:1 open-label fashion to either Inclisiran sodium 300 mg s.c. (administered at Day 1 and Day 90) or to BPA tablets 180 mg p.o. (given once daily). Participants will be required to maintain their background lipid-lowering treatment (maximally tolerated statin dose +/- Ezetimibe) unchanged for the duration of the study. The end of treatment (EOT) is reached at day 150. A Safety-Follow-up call will be conducted 30 days after EOT visit (Day 180). The overall study duration is approximately 190 days but can vary depending on individual screening and the visit windows allowed for the treatment period and EOS visit.

PMCF Study of the CE-marked Drainova® ArgentiC Catheter

The drainova® ArgentiC Catheter initially received the CE mark in 2019 under the Medical Device Directive 93/42/EEC, thus being considered a legacy device under the Medical Device Regulation (EU) 2017/745 (MDR). In order to fulfill the requirements of the MDR, this PMCF study is planned to be conducted to obtain clinical data on the device confirming its safety, performance and clinical benefit in clinical routine according to the instructions for use (IFU). This PMCF study is performed as a purely observational activity within the current standards of care and without additional invasive or burdensome procedures. The drainova® ArgentiC catheter is a catheter indicated for the treatment of patients with pleural effusions and ascites, both in the malignant and non-malignant manifestations.

Study to Evaluate the Effect of Balcinrenone/Dapagliflozin in Patients With Heart Failure and Impaired Kidney Function

The purpose of this study is to investigate the effect of balcinrenone/dapagliflozin compared with dapagliflozin, on the risk of CV death, HF event with and without hospitalisation, in patients with chronic HF, impaired kidney function, and who have had a recent HF event. Eligible patients will randomly be assigned with a 1:1:1 ratio to receive once daily administration of one capsule and one tablet of one of the following treatments: 1. Balcinrenone/dapagliflozin 15 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet 2. Balcinrenone/dapagliflozin 40 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet 3. Dapagliflozin 10 mg tablet and matching placebo for balcinrenone/dapagliflozin capsule The study is event driven, and the average study duration for a participant is estimated to be 22 months including screening period, 20 months blinded treatment period and a one-month follow-up period on open-label dapagliflozin. The study will be conducted at approximately 700 sites in approximately 40 countries globally.