The Effects of Antihistamines on Pre-Pulse Inhibition
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the investigators research is to test whether problems people have with
      processing their senses (feeling overwhelmed, distracted or upset by sounds and other
      stimuli) can be lessened by meclizine, a drug found in many over the counter antihistamines,
      which are medicines used for things like allergies, sleep problems, or the common cold.
    

Detailed description: 
      This experiment will test the efficacy of acute anti-histamine doses on the acoustic startle
      response and prepulse inhibition (or PPI, a well-known neurobehavioral phenomenon used to
      characterize sensorimotor modulation described in detail below) in a male population with
      high baseline sensory startle levels. In addition, sex differences in baseline PPI (i.e.
      without anti-histamine administration) in subjects of this population will be investigated.

      The main hypothesis of the study is that the H1¬-antagonist meclizine will be effective in
      restoring low levels of PPI observed in the subject pool so that sensory gating is made more
      effective. The dependent measures will be startle response magnitude and pre-pulse
      inhibition.

      The experiment will take place in four sessions, carried out on different days. Consecutive
      test sessions will take place no earlier than 3 days, and no longer than 21 days apart.
      Before being recruited into the study, potential participants will go through a phone
      screen-a pre-experiment screening questionnaire (separate) to exclude subjects with
      neurological disorders, certain psychiatric disorders, who smoke or use nicotine products, or
      who use certain drugs (see exclusion criteria below) as they can affect PPI levels. If they
      are eligible per the phone screen, subjects will come in for screening (test day 1). They
      will be again asked about their tobacco/nicotine use and what medications they are currently
      taking. They will be asked about their caffeine history use. Caffeine and caffeine withdrawal
      both have effects on startle response but not on PPI so we are not restricting subject's
      caffeine use, but collecting this information. CO levels will be collected using a CO monitor
      to confirm that participants have not recently used a tobacco product. They will be asked
      questions about psychiatric symptoms, personality, and how they cope with stress.
      Participants' startle responses and PPI will be tested in the laboratory (see below).

      During the following three test days (2-4) before dispensing study drug, male participants
      who qualify, will be asked to fill out a questionnaire about tobacco or nicotine use since
      their previous visit along with assessing any change in their medications (specifically
      verifying that a male participant has not used an allergy, cold/flu medication within 3 days
      of their study visit). If the participant answers yes to either question, they will be asked
      to return to the clinic on a different day: 1) 3 or more days post using an antihistamine or
      2) at least 2 weeks post using tobacco or nicotine. Both antihistamine medications or
      tobacco/nicotine recent use can effect a participant's PPI which is why we have the need to
      ask male participants about any possible changes. They will also be asked how they arrived to
      the clinic to verify that they have a driver who came with them/dropped them off, had a hired
      driver provided by the study if they live in Durham or came by bus or by foot. They will be
      asked about their caffeine use on the day of their experiment. Their baseline sedation level
      will be assessed. On test days 2-4, the test procedure employed on test day 1 will be
      repeated, but 60 minutes before the start of each test sessions, participants will receive a
      placebo, a low (12.5 mg) dose of meclizine, or a high (25 mg) dose of this drug in a
      counterbalanced order.

      Male participants (n = 20) will receive the study medication or placebo orally and will be
      provided water at administration at visits Day 2-4. Placebo and meclizine capsules will be
      identical in shape, size, and color. The randomization and counterbalancing of the order of
      dosing will be in charge of Dr. Levin. In order to ensure that the blind procedure is not
      violated, Dr. Levin (a) will provide the identical capsules for the study to the Study
      Coordinator in containers labeled "Subject X, day Y", and (b) will have no contact with the
      participants in the study. Meclizine and placebo will be dispensed by the Study Coordinator
      under the administrative supervision of Dr. Rosenthal, and under the clinical supervision of
      a study physician. During the resting period between pill ingestion and the experimental
      task, male participants will be asked to sit in a lab room and read or use the internet. At
      20 minutes and 40 minutes post drug, sedation level will be assessed using the scale listed
      below.

      In each PPI test session throughout all 4 visits, male participants will begin with a resting
      baseline period of 5 minutes, where they will be asked to sit quietly and still in a sound
      and temperature controlled lab room, with their eyes open looking at a fixation cross on the
      monitor. Baseline is conducted to obtain measures of emotional arousal and sedation prior to
      the experimental manipulations. As such, during baseline psychophysiological measures will be
      collected. Self-reported emotional arousal will be obtained at the beginning and end of the
      baseline period using the Self-Assessment Manikin (Bradley, 1999), which assesses arousal and
      valence of affective state using Likert (1-9) scales. Self-reported level of sedation will be
      assessed at the same time points as emotional arousal (using a modified Self-Assessment
      Manikin using the same Likert 1-9 scale). Next, participants will be exposed to an initial
      adaptation phase, in order for them to become acquainted with the startle stimuli (pulses and
      prepulses), and their startle responses reach a stable level. In this phase, 4 blocks of
      prepulse-pulse (pP) and pulse-alone (P) trials will be presented, with an inter-trial
      interval (ITI) of 20 seconds (+/- 5 sec). After the initial adaptation phase, participants
      will be instructed to view a computer monitor where random geometric figures will be
      presented, while simultaneously 10 blocks of auditory pP and P trials will be presented with
      an ITI of 20 sec. Each test session will last around 15 minutes. At the end of the test
      session, the standardized lab test to assess the participants' attention level described
      above will be presented again.

      Females will only complete the first day of testing (in the same way as described for male
      subjects above).
    

Intervention name(s): Placebo; Meclizine; Meclizine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Placebo; Meclizine 12.5 mg; Meclizine 25 mg
Other intervention name(s): Sugar Pill; Antivert, Dramamine II, Bonine, Medivert; Antivert, Dramamine II, Bonine, Medivert
Intervention MeSH terms: Meclizine; Dimenhydrinate
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: PPI; Meclizine; Startle; Sensory processing; antihistamines