Clinical trial NCT03270839: Motion Sickness Medications and Vestibular Time Constant
Official title: Motion Sickness Medications and Vestibular Time Constant
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Drug Reaction
Lead sponsor: Medical Corps, Israel Defense Force
Sponsor class: OTHER
First posted: 2017-09-01
Enrollment: 80
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Vestibular Time Constant Change/differential
timeFrame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
measure: Step Velocity Test Gain Change/differential
timeFrame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
measure: Optokinetic After Nystagmus (OKAN) Gain Change/differential
timeFrame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
measure: Optokinetic After Nystagmus (OKAN) Time Constant Change/differential
timeFrame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
measure: Optokinetic After Nystagmus (OKAN) Slow Phase velocity Sum Change/differential
timeFrame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
measure: Pupil Size Change/differential
timeFrame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
measure: Pupil Accommodation and Convergation Change/differential
timeFrame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
measure: Side Effects Questionnaire Change/differential
timeFrame: Baseline at the beginning of session prior to comparator (drug/placebo) receiving, 1 hour after receiving comparator and 2 hours after receiving comparator.
Secondary outcomes:
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Israeli Navy Medical Institute
Study officials:
affiliation: Head of Motion Sickness and Human Performance Laboratory, Principal Investigator
name: Dror Tal, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: Golding JF, Gresty MA. Pathophysiology and treatment of motion sickness. Curr Opin Neurol. 2015 Feb;28(1):83-8. doi: 10.1097/WCO.0000000000000163.
citation: 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.
citation: 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.
citation: 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.
citation: Tal D, Hershkovitz D, Kaminski G, Bar R. Vestibular evoked myogenic potential threshold and seasickness susceptibility. J Vestib Res. 2006;16(6):273-8.
citation: 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.