Conditioning of antihistaminergic effects

The current evidence suggests that it might be possible to condition the
effects of antihistamines, which may lead towards reduction of symptoms and
improvement of quality of life in allergic patients. Discovering the
psychoneuroimmunological mechanisms involved in this process could provide a
basis for new therapeutic possibilities and therapies.

The primary study objective is to investigate effects of conditioning on
self-reported itch in healthy subjects in response to a short-term validated
histamine test. Conditioning effects on other physiological and psychological
parameters will be investigated as well and the possible influence of genetic
variants such as the 5HTTLPR-genotype on conditioning will be explored.

In line with previous conditioning studies and with other studies conducted by
our research group, a randomized placebo-controlled conditioning paradigm
consisting of 2 phases will be applied. In the acquisition phase - consisting
of 3 sessions on 3 consecutive days - an association between an unconditioned
stimulus (UCS, levocetirizine) and a conditioned stimulus (CS, a
distinctive-tasting beverage) will be made. In the evocation phase - 3
consecutive days in the following week - the conditioning effect will be
tested.

Participants will be randomly assigned to 1.) the experimental condition
(acquisition: CS + UCS; evocation: CS + placebo pill), 2.) the open label
condition (acquisition: CS + UCS; evocation: CS + placebo pill), 3.) the
placebo condition (acquisition and evocation: CS + placebo pill) or 4.) the
conditioned not evoked group (acquisition: CS + UCS; evocation: water + placebo
pill).

Bronchodilation and self-reported wellbeing will be measured repeatedly, and
heart rate and skin conductance continuously during the evocation sessions.
Prior to conditioning and during the final evocation session, participants will
be exposed to histamine through transdermal iontophoresis, which will induce a
short-term skin response and itching sensation. Additionally, the study will
explore whether conditioning of antihistaminergic effects influences blood
serum levels of cytokines and other markers of the immediate inflammatory
response.

Conditioning takes place in the first 3 days of the acquisition phase, i.e. in
the experimental, open label and conditioned not evoked groups, Histamine-1
receptor responsiveness to histamine will be suppressed by administration of
the oral antihistamine levocetirizine (5 mg). In the open label group,
participants will additionally be told about the conditioning procedure and
which group they are in.

Participants need to invest a total of 8 hours into the study, spread out over
7 sessions varying from 15 minutes (acquistion sessions) to 2,5 hours (final
evocation session). Given the nature, dosage, restricted number of days of
administering, the relatively short half-life of levocetirizine and the healthy
study population, no adverse side effects are expected. Blood sampling at the
first and final session will be performed by trained medical personnel with
access to hospital facilities. The symptoms of transdermal histamine
iontophoresis (local swelling, itch, and flare) will disappear within two
hours. All other measurements are considered minimally invasive. Participants
will receive a total reimbursement of ¤ 150,00 for the study.