A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients

We wanted to examine tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating major depressive disorder (MDD). This was a Phase 1B, double blind, randomized, placebo controlled, multiple-dose study with three cohorts. The first cohort received 40 mg q.d. (n=6) or placebo (n=2), the second cohort 40 mg b.i.d. (n=6) or placebo (n=2), and the third cohort 40 mg t.i.d. (n=6) or placebo (n=2). Twenty-four patients with MDD were recruited, with the diagnosis and severity confirmed through remote interviews. Eligible patients received NSI-189 or placebo for 28 days in an inpatient setting with assessments for safety, pharmacokinetics (PK) and efficacy. Outpatient follow-up visits were conducted until day 84 (±3). NSI-189 was relatively well tolerated at all doses, with no serious adverse effects. NSI-189 area under the curve increased in a dose-related and nearly proportional manner across the three cohorts, with a half-life of 17.4–20.5 h. The exploratory efficacy measurements, including Symptoms Of Depression Questionnaire (SDQ), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions—Improvement (CGI-I), and The Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ) showed a promising reduction in depressive and cognitive symptoms across all measures for NSI-189, with significant improvement in the SDQ and CPFQ, and a medium to large effect size for all measures. These improvements persisted during the follow-up phase. In summary, NSI-189 shows potential as a treatment for MDD in an early phase study. The main limitation of this preliminary study was the small sample size of each cohort

All-Ukrainian Sports Event “Olympic Stork” as a New Form of Fitness and Sports Activities Among Students (in the Example of Lviv Schools)

У статті розглянуто особливості впровадження нового спортивно-масового заходу дітей шкільного віку, який ініційовано Національним олімпійським комітетом України – Всеукраїнського спортивно-масового заходу серед дітей та юнацтва “Олімпійське лелеченя” на прикладі школярів міста Львова. Завдання дослідження: 1) проаналізувати роль та значення спортивно-масових змагань у системі фізичного виховання дітей і підліт-ків; 2) опрацювати досвід упровадження пілотного проекту НОК України Всеукраїнського спортивно-масового заходу серед дітей та юнацтва “Олімпійське лелеченя” у 2010–2011 навчальному році та особливості реалізації цього проекту в 2011 – 2012 навчальному році; 3) вивчити особливості організації, проведення й методичного супроводу Всеукраїнського спортивно-масового заходу серед дітей та юнацтва “Олімпійське лелеченя” серед школярів 5–6-х класів загальноосвітніх шкіл міста Львова; 4) проаналізувати ставлення шко-лярів середнього шкільного віку до нового заходу, який ініціював НОК України – “Олімпійське лелеченя”. Визна-чено, що успішне впровадження “Олімпійського лелеченяти” в практику шкільного фізкультурно-спортивного руху України істотно сприятиме активізації позакласної та позашкільної фізкультурно-спортивної роботи, сприятиме залученню дітей та підлітків до активних занять спортом, пропаганді олімпійських цінностей та ідеалів серед школярів і педагогів України. The paper considers features of implementation of new sports event among schoolchildren that was initiated by the National Olympic Committee of Ukraine – All-Ukrainian sports event among children and youth “Olympic stork” in the example of schoolchildren of Lviv. Tasks of research: 1. Analyze the role and importance of sports and mass events in the system of physical education of children and adolescents. 2. Consider the experience of implementation a pilot project NOC of Ukraine All-Ukrainian sports event for children and youth “Olympic stork” in the 2010–2011 school year and feature of realization of this project in 2011–2012 school years. 3. Investigation of the organization, conduct and methodical accompaniment of the All-Ukrainian sports-event among children and youth “Olympic stork” among pupils of 5–6 grades of the city. 4. To analyze the relation of schoolchildren of middle school age to the new measure that initiated NOC of Ukraine is “Olympic stork”. Certainly, that successful introduction of “Olympic stork” in practice of school physical culture – sporting motion of Ukraine will be instrumental in a substantial rank activation of extracurricular and out-of-school physical culture-sporting work, will be instrumental in bringing in of children and teenagers to active going in for sports, promoting of Olympic values and ideals among schoolchildren and teachers of Ukraine

IMPLEMENTING A MEMORY CLINIC MODEL TO FACILITATE RECRUITMENT INTO EARLY PHASE CLINICAL TRIALS FOR MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE

Background: The recruitment challenges for MCI and AD subjects into clinical trials are well known, and this is particularly true for early phase studies. Currently, only 10-20% of all patients who are referred for research from the community are trial eligible (Grill and Karlawish, 2011). Due to the limited and specific study objectives in early phase study designs, these rates drop to approximately one patient every two months. Barriers to research recruitment are multi-factorial, involving patient centered factors, issues related to caregiver/study partner participation, and aspects related to the involvement of their treating physicians. To address this challenge, we implemented a Memory Clinic within PAREXEL’s Early Phase Clinical Pharmacology Unit. Our objective was to significantly facilitate recruitment into AD clinical trials by providing resources and education to patients, their treating physicians, and caregivers in the community. Method: The Clinic’s primary goals were to increase research visibility and partnerships with local organizations and referring physicians. Members of the research team co-sponsored community outreach events with local organizations, thereby increasing awareness about the services of this memory clinic. Secondly, physician outreach was expanded to include those who were not previously amenable to clinical trial referrals. Finally, Memory Clinic patients were given clinical evaluations, free of charge and the results were discussed with the patients and their caregivers. If the patients were interested in hearing more about possible research opportunities, they were referred to the early phase unit for a screening visit. Results: We found that new referrals for research participation significantly increased as a result of this new paradigm. In 2016, 12 patients diagnosed with MCI or AD per protocol, were referred to a research study and 3 were randomized. In 2017, 98 patients were referred and 16 were enrolled In addition, our referral network increased with 30 physicians over a 20 mile radius. Collaborations with national non-profit organizations also increased, thereby increasing public awareness about the importance of research participation in the development of new treatments for Alzheimer’s Disease. Conclusions: In summary, community engagement and providing referring physicians with a clinical service improved recruitment significantly for our phase 1 unit. Resource education, staff training, and dedicated medical professionals can significantly improve awareness about clinical research participation and provide additional participants over and above traditional recruitment methods and trial registry enrollment in a large urban area.</jats:p