Traffic noise-induced sleep disturbances and their correction by an anxiolytic sedative, OX-373.

In a double-blind, placebo-controlled study the effect of nocturnal traffic noise and bedtime medication of a new benzodiazepine, OX-373, on objective and subjective sleep variables as well as on the quality of morning awakenings was investigated. 10 healthy subjects spent 17 nights in the sleep laboratory: 2 adaptation nights, 1 baseline night, 4 drug nights (20, 30, and 40 mg OX-373 and placebo) and 4 subsequent wash-out nights as well as 3 nights under traffic noise with placebo, 30 and 40 mg OX-373 and 3 subsequent wash-out nights. Nocturnal traffic noise with an intensity of 45-65 dB(A) induced sleep disturbances characterized by an increase in intermittent wakefulness and stage 1 and the number of nocturnal awakenings as well as by a decrease of spindle and REM sleep stages. Subjectively, a decrease of deep sleep and increase of light sleep and middle insomnia was reported. Upon awakening in the morning, mood was significantly deteriorated. The new benzodiazepine OX-373 attenuated the above-described traffic noise-induced changes and produced even oppositional alterations, such as a decrease in stage 1, number of awakenings and stage shifts while increasing stage 2. The drug alone decreased the number of awakenings and stage 1 and augmented stage 4 as compared with placebo, which was subjectively felt as an increase in deep sleep and as a decrease of light sleep, early and middle insomnia. In the morning, there were no signs of 'hangover', which was confirmed also by psychometry. Nor were there any clinically relevant alterations in blood pressure and pulse. Thus, our studies confirmed earlier pharmaco-EEG and psychometric investigations predicting OX-373 as well-tolerated anxiolytic sedative, and suggested further that traffic noise could eventually be utilized as an experimental provocative technique in order to induce a standardized sleep disturbance for early clinical drug evaluation of potentially hypnotic substances.

RCT Entities:   Population Interventions Outcomes