|- candidate number||8122|
|- NTR Number||NTR2357|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||6-jun-2010|
|- Secondary IDs||ABR 32831 CCMO|
|- Public Title||The effect of nicotine on attention.|
|- Scientific Title||The Neurobiological Basis of Disengagement: A Mechanism Implicated in Visuospatial Attention.
|- ACRONYM||The neurobiology of disengagement|
|- hypothesis||It is expected that:|
1. Cholinergic agonism by nicotine (Nicorette mint 2mg) will result in a facilitation of disengagement of attention;
2. Cholinergic agonism will not affect bias.
|- Healt Condition(s) or Problem(s) studied||Attention, Nicotine|
|- Inclusion criteria||Participants must be male and between 18-40 years old.|
|- Exclusion criteria||1. Hypersensitivity to nicotine or other substances in the chewing-gum;|
2. Oral infection or pharyngitis;
3. Active oesophagitis;
4. (History of) cardiovascular disease;
5. Liver failure / insufficiency;
6. Kidney failure / insufficiency;
7. Diabetes mellitus;
8. Use of medication.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||9-aug-2010|
|- planned closingdate||9-feb-2011|
|- Target number of participants||32|
|- Interventions||Participants will be presented two sessions (placebo/nicotine, sessions are separated by at least a week). In each session, before and after nicotine or placebo intake, participants will be assessed with respect to disengagement and bias. Nicotine will be given as Nicorette mint 2mg.|
|- Primary outcome||Independent variable: Cholinergic agonism.
In the Visual Spatial Cueing (VSC) paradigm the dependant variables are:
1. The validity effect in ms, specifically, reaction time validly cued targets minus reaction time invalidly cued targets (Both bias and disengagement related);
2. Parietal cue ERP components (EDAN + LDAP ERP components) (Bias related);
3. P1 validly cued target ERP (Bias related);
4. LPD invalidly cued target ERP (Disengagement related).
In the stop task paradigm the dependant variables are:
1. Stop signal reaction time (SSRT) in ms (both bias and disengagement related);
2. N2 stop signal ERP (Disengagement related);
3. LPD stop signal ERP (Disengagement related).
It is expected that facilitated cholinergic neurotransmission by nicotine will result in increased disengagement but will not affect bias.
|- Secondary outcome||Independent (subject) variable: Smoking.|
Dependent variables are the same as listed above.
After placebo, nicotine abstinent smokers will have reduced disengagement (as reflected in EEG and behavioural measures) as compared to healthy subjects. No difference is expected with regard to bias.
|- Timepoints||At 30 min post nicorette administration, computertasks are performed and EEG is recorded. Total duration of each session (placebo / nicotine) is approximately 4.5 hours.|
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||MSc. H.N.A. Logemann|
|- CONTACT for SCIENTIFIC QUERIES||MSc. H.N.A. Logemann|
|- Sponsor/Initiator ||Utrecht University (UU)|
(Source(s) of Monetary or Material Support)
|- Brief summary||For the development of better pharmacological treatment of various disorders in which attention and impulsivity are implicated, such as ADHD, it is of crucial importance to acquire more knowledge on their neurobiological basis. Two functional brain mechanisms that are implicated in visual spatial attention are bias and disengagement. Here, bias refers to increased sensory information processing due to the orientation of attention. Disengagement refers to the interruption of that attentional set, making processing of non attended stimuli possible. The dominant theory posits that cholinergic neurotransmission underlies bias, and disengagement rests on noradrenergic neurotransmission. However, results of pharmacological studies are inconsistent. Scrutinizing the results of pharmacological research suggests the opposite of the dominant model. Therefore a new model is proposed which specifically states that bias rests on noradrenergic neurotransmission and that disengagement rests on cholinergic neurotransmission. Recently we started a University Medical Center (UMC) Utrecht METC (IRB) approved study aimed at testing the noradrenergic part of the model using Clonidine. In the current study, our aim is to test the second – cholinergic - part of the model. Since behavioral outcome reflects activity in both, disengagement and bias related mechanisms, studying brain activity is crucial. Therefore we incorporate EEG in combination with two computer tasks to investigate bias and disengagement associated brain indices (i.e., event-related potentials; ERPs). Firstly, we expect that cholinergic agonism by Nicorette mint (2mg) improves disengagement in two samples, smokers and non-smokers. Secondly we expect that nicotine abstinent smokers may have disengagement related dysfunction. Hypotheses will be tested in two samples, smokers and non-smokers. Participants will be presented two sessions (placebo/nicotine, sessions are separated by at least a week). In each session, before and after nicotine or placebo intake, participants will be assessed with respect to disengagement and bias. The burden and risks associated with the tasks and pharmacological manipulation are expected to be negligible.|
|- Main changes (audit trail)|
|- RECORD||6-jun-2010 - 6-feb-2011|