|- candidate number||5245|
|- NTR Number||NTR1650|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||1-feb-2009|
|- Secondary IDs|| |
|- Public Title||The Pharmacology of Attention.|
|- Scientific Title||The neurobiological basis of bias and disengagement;
Two neurotransmitter mechanisms implicated in visual spatial attention.|
|- ACRONYM||The Neurobiological Basis of Bias and Disengagement.|
|- hypothesis||In line with results from recent pharmacological studies, it is expected that: |
1. Inhibiting the cholinergic system by Inversine (Mecamylamine Hydrochloride) results in an impairment of disengagement, but will not affect bias;
2. Inhibiting the noradrenergic neurotransmitter system by Clonidine will result in an impairment in Bias, but will not affect disengagement.
|- Healt Condition(s) or Problem(s) studied|
|- Inclusion criteria||1. Participants must be between 18 – 40 years old;|
2. Passing the medical screening (in which cardiovascular functioning and blood pressure is evaluated) is a prerequisite.
|- Exclusion criteria||1. Use of any medication;|
2. Low blood pressure, systolic bp under 100 mmHg, diastolic under 70 mmHg.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mei-2009|
|- planned closingdate||1-mrt-2010|
|- Target number of participants||48|
|- Interventions||Pilot is a drug-free pilot aimed to verify results (ERPs / behavioral data) of previous studies, 12 participants will be included.
The final study will contrast clonidine (0.1mg) and placebo. Like the pilot, the duration of each condition is 4.5 hours. In this study, 24 participants will be included. The minimal time between conditions is one week.
|- Primary outcome||1. Behavioural measures;|
2. In the Visual Spatial Cuing (VSC) paradigm: the validity effect in ms (RT valid cued target - RT invalid cued target).
A larger validity effect reflects either more bias, or less disengagement;
3. In the stop task paradigm: the stop signal reaction time (SSRT); SSRT reflects
inhibition and related disengagement;
4. Neurophysiological EEG (ERP) endparameters in the VSC:
A. Parietal cue ERP components (ADAN + LDAP), related to bias;
B. P1 valid cued target ERP, related to bias;
C. LPD invalidly cued target ERP, related to disengagement.
5. Neurophysiological (ERP) endparameters in the stop task:
A. N2 stop signal ERP, related to disengagement;
B. LPD stop signal ERP, related to disengagement.
|- Secondary outcome||N/A|
|- Timepoints||At approximately t=120 min. post drug ingestion, computertasks are performed and EEG is simultaneously recorded.
|- 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 |
(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. Since behavioral outcome reflects activity in both mechanisms, studying brain activity is crucial. Therefore, hypotheses will be tested by evaluating the effects of cholinergic and noradrenergic antagonism not only on behavioral measures, but explicitly on bias and disengagement associated functional brain indices (i.e., event-related potentials; ERPs).|
|- Main changes (audit trail)||06-Feb-2011: The mecamylamine condition has been expired because mecamylamine was unobtainable by the time the MEC-approval was received. Secondly, the dosage of clonidine has been reduced to 0,1 mg because the burden of 0,2 mg was too heavy. This amendment has been approved on 19-Jul-2010 - NM|
Original Pilot 2: 12 participants will receive two conditions (each about 4.5 hours), Mecamylamine 10mg and placebo. If no effect of mecamylamine is found, the pilot is repeated with 15mg of mecamylamine.
|- RECORD||1-feb-2009 - 29-mei-2011|