ABSTRACT
SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington's disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington's Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression.
ABSTRACT
INTRODUCTION: An experiment in a program of research supporting the sense-assess-augment (SAA) framework is described. The objective is to use physiological measures to assess operator cognitive workload in remotely piloted aircraft (RPA) operations, and provide augmentation to assist the operator in times of high workload. In previous experiments, physiological measures were identified that demonstrate sensitivity to changes in workload. The current research solely focuses on the augmentation component of the SAA paradigm. This line of research uses a realistic RPA simulation with varying levels of workload. METHODS: Recruited from the Midwest region were 12 individuals (6 women) to participate in the experiment. The subjects were trained to perform a surveillance task and a tracking task using RPAs. There was also a secondary task in which subjects were required to answer cognitive probes. A within subjects factorial design was employed with three factors per task. Subjective workload estimates were acquired using the NASA-TLX. Performance data were calculated using a composite scoring algorithm. RESULTS: Augmentation significantly improved performance and reduced workload in both tasks. In the surveillance task, augmentation increased performance from 573.78 to 679.04. Likewise, augmentation increased performance in the tracking task from 749.39 to 791.81. Augmentation was more beneficial in high workload conditions than low workload conditions. DISCUSSION: The increase in performance and decrease in workload associated with augmentation is an important and anticipated finding. This suggests that augmentation should only be provided when it is truly needed, especially if the augmentation requires additional assets and/or resources.Gruenwald CM, Middendorf MS, Hoepf MR, Galster SM. Augmenting human performance in remotely piloted aircraft. Aerosp Med Hum Perform. 2018; 89(2):115-121.
