Combination of Intranasal Scopolamine and Sensory Augmentation to Mitigate G-transition Induced Motion Sickness and Enhance Sensorimotor Performance

Study Overview
=================
Brief Summary
-----------------
The primary specific aim is to evaluate the use of intranasal scopolamine gel and sensory augmentation as an integrated countermeasure to mitigate motion sickness and enhance sensorimotor performance. The proposed intranasal scopolamine gel formulation (Defender Pharmaceuticals, Inc.) offers a safe non-invasive method to self-administer with a rapid onset of action. This study involves a comparison of motion sickness outcome measures when administering intranasal scopolamine gel versus placebo (Aim 1a), and then when administering intranasal scopolamine gel versus placebo with a sensory augmentation belt (Aim 1b).

Detailed Description
-----------------
The primary specific aim is to evaluate the use of intranasal scopolamine gel (DPI-386) and sensory augmentation (SA) as an integrated countermeasure to mitigate motion sickness and enhance sensorimotor performance. The proposed intranasal scopolamine gel formulation (Defender Pharmaceuticals, Inc.) offers a safe non-invasive method to self-administer with a rapid onset of action. The proposed sensory augmentation will utilize vibrotactile feedback of pitch and roll tilt using a portable belt (Engineering Acoustics, Inc.). The investigators will utilize exposure to simulated capsule wave motion on a 6DOF platform to provide an operationally relevant platform to induce motion sickness and impair performance on functional tasks. The investigators hypothesize that the combination of intranasal scopolamine gel and sensory augmentation of Earth vertical will be more effective to mitigate motion sickness and improve task performance than when administered separately. Using a randomized double-blind cross-over design, the investigators will compare motion sickness symptom severity and time to endpoint (symptom level defined as severe malaise) in 30 subjects during exposure to simulated wave motion on a 6DOF platform inside of a crew capsule mockup. The investigators will compare four conditions: (1) intranasal scopolamine gel (0.4 mg) with sensory augmentation, (2) intranasal scopolamine gel (0.4 mg) without sensory augmentation, (3) placebo control with sensory augmentation, and (4) placebo control without sensory augmentation. The wave motion stressor will begin 30 min post drug administration and will not exceed 45 min in duration. Performance on a series of functional tasks (dual-task tracking and eye-hand target acquisition) will be performed pre, during, immediately post, and following 15 min of recovery of each test. The bioavailability of scopolamine for each session will be estimated from plasma concentrations obtained at drug administration and then every 15 min up to 2-hr post-dosage. Subjective side effects and performance on the Psychomotor Vigilance Test (PVT) will also be obtained at 15 min intervals. A small pilot study including 10 subjects tested once each will be performed to verify the experimental protocol including that the simulated capsule wave motion will provoke motion sickness symptoms. These pilot sessions will not include the medication nor the blood sampling.

Official Title
-----------------
Optimizing the Combination of Intranasal Scopolamine and Sensory Augmentation to Mitigate G-transition Induced Motion Sickness and Enhance Sensorimotor Performance

Conditions
-----------------
Motion Sickness, Space, Motion Sickness, Sea Sickness

Intervention / Treatment
-----------------
* Drug: DPI-386 Nasal Gel
* Drug: Placebo Nasal Gel
* Drug: DPI-386 Nasal Gel
* Drug: Placebo Nasal Gel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects should be minimally susceptible to provocative motion as evidenced by at least two responses on the Motion Sickness Susceptibility Questionnaire of Sometimes or Frequently. No participants should have neurologic, vestibular or autonomic disorders, or medical conditions that could be worsened by scopolamine (narrow-angle glaucoma or urinary retention Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) negative test, confirmed by Food and Drug Administration (FDA) authorized COVID-19 test < 7 days prior to study drug administration or no COVID 19 symptoms up to 10 days prior to study drug administration. Exclusion Criteria: Subjects will be excluded if they are taking other drugs that are capable of causing CNS effects such as antihistamines, tricyclic antidepressants, and muscle relaxants or have hypersensitivity to scopolamine or other belladonna alkaloids or to any ingredient or component in the formulation or delivery system. Pregnant women are excluded from participation. Women of child-bearing potential will be offered a pregnancy screening test and excluded with a positive test.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DPI-386 Nasal Gel<br>DPI-386 Nasal Gel, 0.4 mg | Drug: DPI-386 Nasal Gel<br>* Subjects will self-administer DPI-386 Nasal Gel.<br>* Other names: scopolamine;|
| Experimental: Placebo Comparator<br>Placebo Nasal Gel | Drug: Placebo Nasal Gel<br>* Subjects will self-administer Placebo Nasal Gel.<br>|
| Experimental: DPI-386 Nasal Gel and Sensory Augmentation DPI-386 Nasal Gel, 0.4 mg<br>8-Channel K-Tactile Belt, Engineering Acoustics, Inc., Casselberry, FL | Drug: DPI-386 Nasal Gel<br>* Subjects will self-administer DPI-386 Nasal Gel. Vibrotactile feedback of tilt direction and magnitude will be provided on a sensory augmentation belt worn by the subject.<br>* Other names: scopolamine;|
| Experimental: Placebo Comparator and Sensory Augmentation Placebo Nasal Gel<br>8-Channel K-Tactile Belt, Engineering Acoustics, Inc., Casselberry, FL | Drug: Placebo Nasal Gel<br>* Subjects will self-administer Placebo Nasal Gel. Vibrotactile feedback of tilt direction and magnitude will be provided on a sensory augmentation belt worn by the subject.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motion sickness (MS) symptom severity using Pensacola Diagnostic Index (PDI) scale | The PDI scale ranges from 0 to 16 with higher numbers reflecting greater symptom severity (in this study a PDI score of 8 will be used as a motion sickness (MS) endpoint). During each session, the primary motion sickness symptoms will be recorded every minute during the capsule wave motion stimulation through the MS endpoint (PDI score ≥ 8 points) up to 45 min total. | 45 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motion sickness symptom severity using a Subjective Discomfort Rating (SDR) | The SDR scale ranges from 0-20 with higher numbers reflecting greater symptom severity (20 = vomiting). This will be recorded at the same interval as the PDI score. | 45 minutes | 
| Time to MS endpoint (based on PDI score of 8 points) | The time to MS endpoint will be recorded once per session, range of 0-45 with higher numbers reflecting less motion sickness susceptibility. | 45 minutes | 
| Performance measures: response time | Response time during eye-hand coordination tasks will be recorded once every 15 min of stimulation (up to three measures per session) with the shorter response representing better performance. | 45 minutes | 
| Performance measures: error | Response error during eye -hand coordination tasks will be recorded once every 15 min of stimulation (up to three measures per session), with lower error representing better performance. | 45 minutes | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
wave motion, eye-hand coordination, artificial horizon