Prove the Feasibility of a Non-invasive Means to Identify Temporary Neurological Impairment Resulting From the Use of a Commonly Prescribed Opioid by Identifying an Oculomotor Biosignature Associated With Temporary Neurologic Impairment in Pain-free Opioid-naïve Subjects, and to Initiate the Development of Such a Signature.
Conditions: Neurologic Impairment by Opioids
Sponsor: Zxerex Corporation

Study Project: Non-intrusive detection of temporary neurologic impairment by opioids
Award #: 1R43DA049684-01
NCT #: Pending
Date: 07.28.2022
Document Type: Study Protocol & Statistical Analysis Plan (SAP)

Study Protocol & Procedures
The objective of this study is to ascertain the influence of impairment by oxycodone on the oculomotor system as
measured by an infrared videographic eye tracking system. Specifically:
●
Measurement of opioid-induced changes in oculomotor activity, with respect to undosed (control)
and placebo conditions
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Comparison of opioid-induced oculomotor effects from low- and high-dose treatments, to describe
a dose-response effect, if present
Subjects are  tested for oculomotor effects of ingested oxycodone, using an SR EyeLink 1000 eye tracking device
consisting of an infrared camera, console and control equipment to sample orientation and pupil size at 500 frames
per second. Binocular orientation, eye movement, and pupil area were collected, with the eye movements
characterized as involuntary microsaccades (occurring during fixational events) or intentional saccades (movement
between fixational events). Subjects were subjected to several randomly ordered visual tests, including visual
fixation, saccade speed and accuracy, cognitive control over saccades, cognitive control over visual scanning,
pursuit and activity during free viewing of randomly presented images. These tests required subjects to watch or
follow a stimulus consisting of a small annulus over a gray background. An additional test measured pupillary
reactivity to sudden changes in screen illumination.
Tests were conducted over three different sessions, each consisting of three 40-min timeblocks, separated by
30-min rest periods. Each timeblock contained two cycles of each eye-tracking test, and one sequence testing
pupil reactivity. Data were collected in the control, placebo, low-dose oxycodone (5 mg) and high-dose oxycodone
(10 mg) conditions.
STATISTICAL PROCEDURES
Eye tracking time series are processed with blink detection and feature extraction procedures. Saccadic and
microsaccadic movements were then detected using a modified Engbert algorithm (R Engbert, R Kliegel, Psychol.
Sci. 15(6), 2004). Test-specific features (whose full descriptions are withheld as trade secrets) of microsaccade
data were analyzed using 2-way linear ANOVA models: the effect of Condition is evaluated against the effect of
Trial (1-6) to identify significant dose-dependent changes. Features of saccade data (combined across trials to
achieve satisfactory sample size) were compared between Condition levels using a 1-way ANOVA. Features that
exhibited effects of Condition in the first analysis were tested with post hoc t-tests to evaluate the presence of
dose-dependent effects. The effect of acute eye fatigue is also investigated with another 2-way ANOVA of
Condition and Trial effects: in this case, the Trial comparisons were the first trial in each timeblock (Trials 1, 3, 5)
versus the second trial in each timeblock (Trials 2, 4, 6).
After the opioid effects on oculomotor behavior are established, a binary classifier will be constructed to accurately
predict opioid impairment. High-dose and low-dose opioid conditions were combined into an opioid condition,
which will be evaluated against the combined placebo and control conditions, for all test types.