Motion Sickness Medications and Vestibular Time Constant

Overview

Sea sickness represents a major limitation on the performance of ships' crew. One of the challenges faced by the physician in the motion sickness clinic when prescribing anti-sea sickness medication is to select the appropriate drug for the patient. Difficulties arise due to high variability in the response to different drugs. In the case of sea sickness, the current procedure is to examine the drug's efficacy in each individual during real time exposure to sea conditions. A number of studies have documented the presence of sea sickness drug receptors in the vestibular nuclei, which determine the vestibular time constant. Two clinical vestibular tests which evaluate the time constant are the Velocity Step and OKAN tests. The purpose of the proposed study is to evaluate the influence of motion sickness drugs on the vestibular time constant, as a possible bioequivalent of drug potency in the individual subject. Eighty crew members will be recruited and divided into groups responsive and non-responsive to the sea sickness drugs scopolamine and meclizine. Subjects having a Wiker score of 7 in waves 1 meter high without drug treatment, and no improvement in symptoms after treatment will be defined as non-responsive to sea sickness drugs. Subjects having a Wiker score of 7 in waves 1 meter high without drug treatment, and a Wiker score of 4 or less after treatment, will be defined as responsive to drug therapy. Kwells, Bonine and placebo, will be assigned to each subject in a random, double-blind fashion. Each group will perform the Velocity Step and OKAN tests before, one and two hours after drug or placebo administration.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Other
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: March 1, 2018

Interventions

  • Drug: Bonine 25Mg Chewable Tablet
    • Motion sickness drug
  • Drug: Kwells
    • Motion sickness drug
  • Drug: Placebo Oral Tablet
    • No active substance in the tablet

Arms, Groups and Cohorts

  • Active Comparator: Responsive to Scopolamine (Active)
    • Scopolamine administration – subject will take 1 tablet per os (Kwells, Hyoscine Hydrobromide 0.3mg, 1*day )
  • Placebo Comparator: Responsive to Scopolamine (Placebo)
    • Placebo administration – subject will take 1 tablet per os (Placebo Oral Tablet, no active substance in the tablet)
  • Active Comparator: Non-responsive to Scopolamine (Active)
    • Scopolamine administration – subject will take 1 tablet per os (Kwells, Hyoscine Hydrobromide 0.3mg, 1*day )
  • Placebo Comparator: Non-responsive to Scopolamine (Placebo)
    • Placebo administration – subject will take 1 tablet per os (Placebo Oral Tablet, no active substance in the tablet)
  • Active Comparator: Responsive to Meclizine (Active)
    • Meclizine administration – subject will take 1 tablet per os (Bonine 25Mg Chewable Tablet, Meclizine Hydrochloride 25mg, 1*day )
  • Placebo Comparator: Responsive to Meclizine (Placebo)
    • Placebo administration – subject will take 1 tablet per os (Placebo Oral Tablet, no active substance in the tablet)
  • Active Comparator: Non-responsive to Meclizine (Active)
    • Meclizine administration – subject will take 1 tablet per os (Bonine 25Mg Chewable Tablet, Meclizine Hydrochloride 25mg, 1*day )
  • Placebo Comparator: Non-responsive to Meclizine (Placebo)
    • Placebo administration – subject will take 1 tablet per os (Placebo Oral Tablet, no active substance in the tablet)

Clinical Trial Outcome Measures

Primary Measures

  • Vestibular Time Constant Change/differential
    • Time Frame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
    • One of the parameters measured in step velocity test [Sec]
  • Step Velocity Test Gain Change/differential
    • Time Frame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
    • One of the parameters measured in step velocity test [0-1]
  • Optokinetic After Nystagmus (OKAN) Gain Change/differential
    • Time Frame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
    • One of the parameters measured in optokinetic test [0-1]
  • Optokinetic After Nystagmus (OKAN) Time Constant Change/differential
    • Time Frame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
    • One of the parameters measured in optokinetic test [Sec]
  • Optokinetic After Nystagmus (OKAN) Slow Phase velocity Sum Change/differential
    • Time Frame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
    • One of the parameters measured in optokinetic test [Deg/Sec]
  • Pupil Size Change/differential
    • Time Frame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
    • Using pupil size chart [Mm]
  • Pupil Accommodation and Convergation Change/differential
    • Time Frame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
    • Eye test for drugs side effects.
  • Side Effects Questionnaire Change/differential
    • Time Frame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
    • Questionnaire of drugs’ side effects.

Participating in This Clinical Trial

Inclusion Criteria

  • Healthy soldiers between the ages of 18 to 40, who suffering from sea sickness – 48 hours prior to session without any use of medications – Soldiers who vomit in waves 1.5 meter high without drugs treatment Exclusion Criteria:

  • Anamnestic hearing Impairment – Ear infection of any kind – Pathological finding in an otoneurological examination, witch will be done by a trained neurophysiologist / a physician. In any case of pathological finding, patient will be advised to continue medical assesment. – Vision pathologies the interfere with VNG test. – Withdrawal of informed consent by the patient of any cause.

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: 40 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Medical Corps, Israel Defense Force
  • Provider of Information About this Clinical Study
    • Principal Investigator: Dror Tal, Head of Motion Sickness and Human Performance Laboratory, Principal Investigator – Medical Corps, Israel Defense Force
  • Overall Official(s)
    • Dror Tal, PhD, Principal Investigator, Head of Motion Sickness and Human Performance Laboratory, Principal Investigator
  • Overall Contact(s)
    • Dror Tal, PhD, +972549096080, tldror1@gmail.com

References

Cheung BS, Howard IP, Money KE. Visually-induced sickness in normal and bilaterally labyrinthine-defective subjects. Aviat Space Environ Med. 1991 Jun;62(6):527-31.

Dai M, Raphan T, Cohen B. Prolonged reduction of motion sickness sensitivity by visual-vestibular interaction. Exp Brain Res. 2011 May;210(3-4):503-13. doi: 10.1007/s00221-011-2548-8. Epub 2011 Feb 2.

Golding JF, Gresty MA. Pathophysiology and treatment of motion sickness. Curr Opin Neurol. 2015 Feb;28(1):83-8. doi: 10.1097/WCO.0000000000000163.

Ishiyama A, Lopez I, Wackym PA. Molecular characterization of muscarinic receptors in the human vestibular periphery. Implications for pharmacotherapy. Am J Otol. 1997 Sep;18(5):648-54.

Phelan KD, Nakamura J, Gallagher JP. Histamine depolarizes rat medial vestibular nucleus neurons recorded intracellularly in vitro. Neurosci Lett. 1990 Feb 16;109(3):287-92. doi: 10.1016/0304-3940(90)90009-x.

Pyykko I, Schalen L, Matsuoka I. Transdermally administered scopolamine vs. dimenhydrinate. II. Effect on different types of nystagmus. Acta Otolaryngol. 1985 May-Jun;99(5-6):597-604. doi: 10.3109/00016488509182266.

Tal D, Hershkovitz D, Kaminski G, Bar R. Vestibular evoked myogenic potential threshold and seasickness susceptibility. J Vestib Res. 2006;16(6):273-8.

Bar R, Gil A, Tal D. Safety of double-dose transdermal scopolamine. Pharmacotherapy. 2009 Sep;29(9):1082-8. doi: 10.1592/phco.29.9.1082.

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