Effect of Caffeine Intake in Vestibular Function
Condition: Vertigo; Diseases, Vestibular; Caffeine
MeSH terms: Vertigo; Vestibular Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      Objective: Assess the effect of caffeine in the following vestibular function tests: Cervical
      Vestibular Evoked Potential (cVEMP), Ocular Vestibular Evoked Potential(oVEMP) and Caloric
      Test.

      Methods: Randomized, prospective triple-blind, placebo controlled clinical trial. All
      participants underwent otoscopy, tympanometry, responded to the Profile of Mood State (POMS),
      submitted to the cVEMP, oVEMP and caloric tests. After that they received placebo or caffeine
      capsule (300mg) and repeated the procedures 45 minutes after.
    

Detailed description: 
      Trial design

      This is a randomized, prospective triple-blind, placebo controlled clinical trial approved by
      the institutional review board under protocol number 1.399.322/16. Informed consent was
      obtained after a full explanation of the experimental procedure.

      Participants

      The sample was made up of medical students who agreed to participate as volunteers and had no
      hearing and/or vestibular complaints or other health problems that could affect the
      homeostasis of the vestibular system (problems in the cervical spine, cardiovascular
      problems, migraine, metabolic disorders, hormonal changes, psychiatric disorders,
      neurological diseases, use of prescription drugs continuously, smokers, alcoholics, illegal
      drug users).

      Randomization, allocation and Blinding

      At baseline, study participants were randomized to receive caffeine or placebo at a 1:1
      ratio, by independent statistician. Was used a completely randomized design for two
      treatments which PLAN procedure (SAS 9.4). The allocation was made for a person outside the
      study what identified the capsules in identical packages labeled with the name of the
      participants. The active (caffeine) and placebo (maize starch) capsules were identical in
      color, size, weight, and packaging.

      Interventions

      All participants underwent otoscopy and tympanometry, responded to the Profile of Mood State
      (POMS), submitted to the cVEMP, oVEMP and caloric tests in that order. After that the
      participants received placebo or caffeine capsule (300mg). After 45 minutes the subjects
      again responded to the POMS, repeated the cVEMP, oVEMP and caloric test. The tests were
      performed in a center of rehabilitation of hearing and balance for the same audiologist, with
      the data collection period was 3 months.

      Caffeine consumption

      To determine caffeine consumption a questionnaire which sought to investigate eating habits
      was applied. The participants have to include for each item (coffee, teas, soft drinks,
      chocolate, powdered chocolate, powdered guarana, food supplements and energy drink) the
      amount, kind (i.e. espresso, filter coffee) and brand. Based on these data, the consumption
      was calculated using a preview standardization. From there, the subjects were classified
      according to consumption: sporadic (less than 100mg), light (100 to 299mg), moderate (300 to
      499mg). Those who had higher intakes equal to 500mg / day or more (heavy or very heavy) were
      excluded.

      POMS

      Self-administered instrument that consists of 65 items describing feelings; to them should be
      assigned values from 0 to 4 according to the Likert scale of 5 points (0 -no, 1 - a little, 2
      - more or less, 3 - well, 4 - extremely). The POMS aims to evaluate six factors:
      tension-anxiety (9 items), depression-dejection (15 items), anger-hostility (12 items),
      vigor-activity (8 items), fatigue-inertia (7 items), confusion-bewilderment (7 items), and a
      total mood disturbance score (TMD)

      cVEMP

      VEMP was performed in response to air-conducted stimuli, using alternate 500Hz (Hertz) tone
      bursts presented at 120 dB (decibel) and rate of 5.1 stimuli per second. Bandpass filter of
      10 Hz to 1500 Hz was used, 50ms window and 200 stimulations in each track were standard. Two
      stimulations were recorded on each side, in order to observe the replicability. The stimuli
      were presented via insert earphones. A cleaning of the skin with abrasive paste was performed
      and surface electrodes were affixed using conductive paste. The non inverting electrode was
      placed in the middle part of the sternocleidomastoid, the ground electrode in lower forehead
      and the inverting on the upper forehead. The impedance of the electrodes should be less than
      or equal to 5hms. Subjects were positioned seated and instructed to maintain maximum head
      turn to the side contralateral to the stimulus throughout stimulation.The latency of P1 and
      N1 and the P1N1 amplitude were analyzed in each ear and an asymmetry rate was also analyzed.
      For the last one was used the formula: ǀ amplitude of right ear ǀ - ǀ amplitude of left ear ǀ
      / ǀ amplitude of right ear ǀ + ǀ amplitude of left ear ǀ x 100. To compare the amplitudes in
      each ear before and after tests was used the rate of change formula, consisting of: ǀ
      amplitude of ear before ǀ - ǀ amplitude of ear after ǀ / ǀ amplitude of ear before ǀ + ǀ
      amplitude of ear after ǀ x 100. The investigators considered normal p13 latencies between
      13.9 to 19.2 and from 22.9 to 30.3 n23 and the asymmetry rate and rate of change of up to
      28%.

      oVEMP

      The investigators used the same parameters of stimulation and analysis described in cVEMP.
      Non inverting electrodes were placed on the face just inferior to each eye (inferior oblique
      muscle), reference electrode was placed 1-2cm below contralateral to the stimulus and ground
      electrode in the forehead. The subject was placed in the sitting position and instructed to
      look upward. The latencies of initial negative (nI) and positive (pI) peak were measured.
      They considered normal nI latencies from 10.2 to 11.8 and from 14.7 to17.3 pI.

      Caloric test

      To perform the caloric test the investigators used an air otocalorimeter, and carried out
      four stimulations of 60 seconds each, with a flow of 8 liters per minute: 50C in the right
      ear, 50C on the left, 24C on the left ear and 24C in the right ear, in this order. The
      absolute values and percentages of unilateral weakness or directional preponderance were
      analyzed for each subject in each test. The subjects were considered normal when they showed
      absolute values from 3 to 45, a range of 30% or less in directional preponderance and of less
      than 25% in the unilateral weakness.

      Outcomes

      The primary outcome was the latency waves for cVEMP and oVEMP and absolute and relative
      values for caloric tests. These parameters were chosen for analysis of the primary outcome
      for being these the most well-established parameters for use in clinical practice. The
      secondary outcomes were asymmetry ratio and ratio of change for cVEMP. There were no
      secondary outcomes for oVEMP and Caloric test.

      Statistical analysis

      Non-parametric tests were used seeking statistically describe and compare the two groups -
      caffeine and no caffeine (Mann-Whitney test), the two time points - before and after in each
      group (Wilcoxon signed-rank test) and study the statistical effect of caffeine consumption on
      the other variables (Jonckheere-Terpstra test). It was used a confidence interval of 95%.The
      spreadsheet MS-Excel was used in your version of MS-Office 2013, for the organization of
      data, and IBM SPSS (International Business Machines - Statistical Package for Social
      Sciences), in its version 23.0, to obtain the results.
    

Intervention name(s): Caffeine; Non caffeine
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): capsule: 300mg caffeine; capsule: placebo (maize starch)
Intervention MeSH terms: Caffeine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Diagnostic