PerSurge (NOA-30) phase II trial of perampanel treatment around surgery in patients with progressive glioblastoma.

BACKGROUND: Glioblastoma is the most frequent and a particularly malignant primary brain tumor with no efficacy-proven standard therapy for recurrence. It has recently been discovered that excitatory synapses of the AMPA-receptor subtype form between non-malignant brain neurons and tumor cells. This neuron-tumor network connectivity contributed to glioma progression and could be efficiently targeted with the EMA/FDA approved antiepileptic AMPA receptor inhibitor perampanel in preclinical studies. The PerSurge trial was designed to test the clinical potential of perampanel to reduce tumor cell network connectivity and tumor growth with an extended window-of-opportunity concept. METHODS: PerSurge is a phase IIa clinical and translational treatment study around surgical resection of progressive or recurrent glioblastoma. In this multicenter, 2-arm parallel-group, double-blind superiority trial, patients are 1:1 randomized to either receive placebo or perampanel (n = 66 in total). It consists of a treatment and observation period of 60 days per patient, starting 30 days before a planned surgical resection, which itself is not part of the study interventions. Only patients with an expected safe waiting interval are included, and a safety MRI is performed. Tumor cell network connectivity from resected tumor tissue on single cell transcriptome level as well as AI-based assessment of tumor growth dynamics in T2/FLAIR MRI scans before resection will be analyzed as the co-primary endpoints. Secondary endpoints will include further imaging parameters such as pre- and postsurgical contrast enhanced MRI scans, postsurgical T2/FLAIR MRI scans, quality of life, cognitive testing, overall and progression-free survival as well as frequency of epileptic seizures. Further translational research will focus on additional biological aspects of neuron-tumor connectivity. DISCUSSION: This trial is set up to assess first indications of clinical efficacy and tolerability of perampanel in recurrent glioblastoma, a repurposed drug which inhibits neuron-glioma synapses and thereby glioblastoma growth in preclinical models. If perampanel proved to be successful in the clinical setting, it would provide the first evidence that interference with neuron-cancer interactions may indeed lead to a benefit for patients, which would lay the foundation for a larger confirmatory trial in the future. TRIAL REGISTRATION: EU-CT number: 2023-503938-52-00 30.11.2023.

Trends in food consumption and nutrient intake in Germany between 2006 and 2012: results of the German National Nutrition Monitoring (NEMONIT).

The German National Nutrition Monitoring (NEMONIT) is a longitudinal and nationwide study to assess changes in food consumption and nutrient intake in Germany. A sample of 1840 participants (baseline age: 14-80 years) was drawn from the nationally representative German National Nutrition Survey (NVS) II (2005-2007). The participants have been interviewed by telephone annually since 2008. Food consumption was assessed by two 24-h recalls in the NVS II and the 4 years of NEMONIT (2008-2012/2013), respectively. Energy and nutrient intakes were calculated using the German Nutrient Database 3.02. Diet quality was evaluated using the Healthy Eating Index-NVS (HEI-NVS) II. Time trends were analysed by generalised estimating equation. Consumption of fruit/fruit products and fruit juice/nectar among men and women decreased, whereas consumption of water, soft drinks and coffee/tea increased over the 6-year period. Furthermore, increased consumption of confectionery and animal fats was observed among women. HEI-NVS II did not change since NVS II in both sexes. There were no changes in energy and protein intakes, but carbohydrate intake declined while fat intake increased over time. Regarding micronutrients, a decreasing intake of thiamin, riboflavin and vitamin B6 was observed in both sexes, but intake of Mg, Fe and niacin increased among women over time. In conclusion, food consumption and nutrient intake remained relatively stable between 2005-2007 and 2012/2013 within this German cohort. A few favourable and unfavourable changes were observed. Compared with national dietary guidelines, consumption of food of plant origin remained too low and consumption of meat/meat products remained too high in Germany.

Longitudinal influences of neighbourhood built and social environment on children's weight status.

The objective was to examine longitudinal 4-year-relationships between neighbourhood social environment and children's body mass index-standard deviation score (BMI-SDS) taking into account the built environment. Furthermore, we have analysed the influence of potential interactions between the social environment and family/social data on children's BMI-SDS. Between 2006-2008 and 2010-2012, anthropometric measurements were conducted among 485 children (age at baseline: 6.1 (5.8-6.4)). Socio-demographic characteristics and perception of residential environment were reported by parents. Geographic Information Systems were used to examine street length, number of food outlets and distance to the nearest playground and park/green space within an 800 m Euclidian buffer of each participant address point. Additional data on neighbourhood characteristics (e.g., traffic density, walkability, crime rates) were obtained from the State Capital of Kiel, Germany. In a multivariate model, walkability, street type, socioeconomic status of the district and perceived frequency of passing trucks/buses were associated with BMI-SDS over 4 years, but only neighbourhood SES had an effect on change in BMI-SDS. However, familial/social factors rather than neighbourhood environment (especially social environment) had an impact on children's BMI-SDS over 4 years. Thus, social inequalities in childhood overweight are only partially explained by social neighbourhood environment.