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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Motion Sickness; Sea Sickness; Motion Sickness, Space
• Intervention / Treatment: Drug: DPI-386 Nasal Gel; Drug: DPI-386 Nasal Gel; Drug: Placebo Nasal Gel; Drug: Placebo Nasal Gel

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Barry Feinberg, MD; Phone Number: 314-697-1330; Email: bfeinberg@defenderpharma.com

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77058
      • Recruiting
      • NASA Johnson Space Center Neuroscience Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 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."
2. No participants should have neurologic, vestibular or autonomic disorders, or medical conditions that could be worsened by scopolamine (narrow-angle glaucoma or urinary retention
3. 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:

1. 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.
2. Pregnant women are excluded from participation. Women of child-bearing potential will be offered a pregnancy screening test and excluded with a positive test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DPI-386 Nasal Gel; DPI-386 Nasal Gel, 0.4 mg	Drug: DPI-386 Nasal Gel; Subjects will self-administer DPI-386 Nasal Gel.; Other Names: scopolamine; Drug: DPI-386 Nasal Gel; 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.; Other Names: scopolamine
Experimental: Placebo Comparator; Placebo Nasal Gel	Drug: Placebo Nasal Gel; Subjects will self-administer Placebo Nasal Gel.; Drug: Placebo Nasal Gel; 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.
Experimental: DPI-386 Nasal Gel and Sensory Augmentation DPI-386 Nasal Gel, 0.4 mg; 8-Channel K-Tactile Belt, Engineering Acoustics, Inc., Casselberry, FL	Drug: DPI-386 Nasal Gel; Subjects will self-administer DPI-386 Nasal Gel.; Other Names: scopolamine; Drug: DPI-386 Nasal Gel; 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.; Other Names: scopolamine
Experimental: Placebo Comparator and Sensory Augmentation Placebo Nasal Gel; 8-Channel K-Tactile Belt, Engineering Acoustics, Inc., Casselberry, FL	Drug: Placebo Nasal Gel; Subjects will self-administer Placebo Nasal Gel.; Drug: Placebo Nasal Gel; 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.

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

Collaborators and Investigators

• Sponsor: Repurposed Therapeutics, Inc.
• Collaborators: National Aeronautics and Space Administration (NASA)
• Investigators: Principal Investigator: Scott J Wood, PhD, National Aeronautics and Space Administration (NASA)

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2022
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: April 17, 2023
• First Submitted That Met QC Criteria: May 23, 2023
• First Posted (Actual): June 2, 2023

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 15, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: eye-hand coordination; wave motion; artificial horizon
• Additional Relevant MeSH Terms: Motion Sickness; Space Motion Sickness; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Antiemetics; Gastrointestinal Agents; Adjuvants, Anesthesia; Mydriatics; Scopolamine; Butylscopolammonium Bromide
• Other Study ID Numbers: NASA 0354 (Aim 1)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No