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The effect of inhibition of a transporter on sedation after antihistamine administration.


- candidate number8667
- NTR NumberNTR2609
- ISRCTNISRCTN wordt niet meer aangevraagd.
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR15-nov-2010
- Secondary IDs2010-023861-23 EudraCT-number
- Public TitleThe effect of inhibition of a transporter on sedation after antihistamine administration.
- Scientific TitleThe effect of P-glycoprotein transport inhibition on brain mechanisms of sedation and cognitive impairment following antihistamines in healthy volunteers.
- ACRONYMN/A
- hypothesisIt is hypothesized that the behavioral effect (i.e. slower RT and impaired attention) of a non-sedative antihistamine will be apparent in combination with a Pgp-blocker, but will not be apparent when administered alone. This, because when a non-sedative antihistamine is not pumped out of the brain by the Pgp transporter, the antihistamine is able to bind at the H1R and will cause cognitive side effects, comparable with sedative antihistamines.
- Healt Condition(s) or Problem(s) studiedHealthy subjects, Fatigue, Antihistamines, Attention, fMRI, P-glycoproteintransporter
- Inclusion criteria1. Aged between 18 and 45 years;
2. Healthy volunteers;
3. BMI between 19 and 30;
4. Able to give a written informed consent;
5. Able to understand the protocol and to come to the visits;
6. Use of a contraceptive method (for women).
- Exclusion criteria1. Medical history of major medical, psychiatric illness or surgery which, in the judgement of the investigator, could jeopardize their health or is likely to modify their handling of the study drug;
2. Any non corrected visual defect or locomotor disorder which could interfere with the study;
3. Acute or chronic systemic disease or disorder;
4. History of hypersensitivity to H1 antihistamines, benzimidazoles or lactose;
5. Seasonal allergic rhinitis or urticaria treated by antihistamine;
6. History of alcohol or drug abuse.
- mec approval receivedno
- multicenter trialno
- randomisedyes
- masking/blindingDouble
- controlPlacebo
- groupCrossover
- Type2 or more arms, randomized
- Studytypeintervention
- planned startdate 2-jan-2011
- planned closingdate1-jun-2011
- Target number of participants16
- InterventionsThere are two testdays, with two fMRI scan sessions per testday.

The first (randomly assigned) testday consists of the following treatments:
Before scan 1: Placebo and 90 minutes later, before scan 2: Verapamil 120 mg.

The second testday consists of the following treatments:
Before scan 1: Cetirizine 15 mg and 90 minutes later, before scan 2: Verapamil 120 mg.

Eventually, the placebo condition of day 1 and the cetirizine condition of day 2 are compared, as well as the verapamil condition of day 1 and the verapamil condition of day 2 (with cetirizine still in the body's system) are compared.
- Primary outcomeThe mean reaction time (ms) of the Attention Network Test (ANT).
- Secondary outcomeCognitive tests:
1. The attention network test;
2. The simple reaction time test;
3. MRI resting state;
4. The BOLD signal.
- TimepointsTwo testperiods.
- Trial web siteN/A
- statusstopped: trial finished
- CONTACT FOR PUBLIC QUERIESMSc. Silke Conen
- CONTACT for SCIENTIFIC QUERIESMSc. Silke Conen
- Sponsor/Initiator University Maastricht (UM)
- Funding
(Source(s) of Monetary or Material Support)
University Maastricht (UM)
- PublicationsN/A
- Brief summaryIt is well known that antihistamines produce sedation and that the magnitude of sedation varies between individual drugs. First generation antihistamines are lipophilic. Therefore, they can easily cross the blood-brain barrier (BBB) and block histamine H1-receptors in the central nervous system, which causes the sedation. Because second generation antihistamines are more lipophobic they cause less sedation. However, other factors, such as P-glycoprotein (Pgp) mediated efflux of the BBB may also determine the presence, absence and/or magnitude of sedation. The Pgp transporter can pump drugs out of the brain, resulting in a reduction of undesired effects in the central nervous system. Studies in experimental animals have demonstrated that the Pgp transporter is involved in the lack of sedative effects of certain antihistamines. However, so far, no human studies have been conducted in order to study the effects of the Pgp transporter on sedation caused by antihistamines. In other words, so far there is no data available to confirm whether Pgp inhibition plays a role in the impairing effects of antihistamines in humans as well. Therefore, this study will focus on the effect of the Pgp transporter on antihistamines in healthy volunteers. Taken previous findings into consideration, it is hypothesized that the behavioral effect (i.e. slower RT and impaired attention) of a non-sedative antihistamine will be apparent in combination with a Pgp-blocker, but will not be apparent when administered alone. This, because when a non-sedative antihistamine is not pumped out of the brain by the Pgp transporter, the antihistamine is able to bind at the H1R and will cause cognitive side effects, comparable with sedative antihistamines.
- Main changes (audit trail)
- RECORD15-nov-2010 - 6-jul-2012


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