An interventional study of Placebo and Nicotine in no Condition, Basic Science, sponsored by University of Maryland, Baltimore. Withdrawn. Open to participants aged 21 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-08-19.
Sponsored by University of Maryland, Baltimore · Not applicable, Interventional, and Basic science
To test whether specific aspects of the attention-enhancing effects of nicotine may be mediated by down-stream activation of alpha1 adrenoceptors, the interaction of nicotine and the alpha1 adrenergic antagonist prazosin on cognitive task performance will be tested in human non-smokers. The effects of a low-dose nicotine patch vs. a placebo patch will be tested in the presence and absence of prazosin over 4 test sessions.
Drugs that activate nicotinic acetylcholine receptors (nAChRs), such as nicotine, have cognitive enhancing, and in particular attention-enhancing effects that may be of clinical benefit to individuals with cognitive deficits, such as those diagnosed with Alzheimer's disease, schizophrenia, or ADHD. nAChR agonists can increase the release of other neurotransmitters in the brain, including dopamine, noradrenaline, serotonin, glutamate and GABA. To date, it is unknown which of these actions is central to mediating the attention-enhancing effects of nAChR agonists. Such knowledge would channel drug development efforts onto subtypes of the nAChR expressed on and activating the target system, but not systems such as the subcortical dopamine system involved in unwanted effects of nAChR agonists (e.g., dependence).
Preclinical studies have suggested that the noradrenergic system is critical to the attention-enhancing effects of the prototypical nAChR agonist nicotine. Activation of alpha1-adrenergic receptors appears to be involved in broadening the attentional window, an effect shared with nicotine. The aim of the present study is to test whether the effects of nicotine on broad monitoring may be mediated by alpha1 adrenoceptors by testing the interaction of nicotine and the predominantly alpha1 adrenergic antagonist prazosin in healthy human non-smokers. The effects of a low-dose nicotine patch vs. a placebo patch will be tested in the presence and absence of prazosin in a 2 x 2 within-subject design, over 4 repeated test sessions, in healthy never-smokers. Each participant is asked to complete for test session, on separate days. In each session, a skin patch will be applied and a capsule given by mouth. In one session, both are a placebo. In another session, the patch contains nicotine (7 mg/24 hrs) and the capsule is a placebo. In another session, the patch is a placebo and the capsule contains 1 mg of prazosin. In another session, the patch contains nicotine and the capsule contains prazosin. The sequence of these testing conditions is counterbalanced and double-blind.
Exclusion Criteria:
Over four test days, each participant will be tested with placebo, nicotine alone, prazosin alone, and nicotine + prazosin, in a double-blind sequence.
Drug: Placebo · Drug: Nicotine · Drug: Prazosin · Drug: Nicotine + Prazosin
placebo skin patch + placebo capsule
nicotine patch (7 mg/24 hrs) + placebo capsule
placebo patch (7 mg/24 hrs) + prazosin capsule (1 mg)
nicotine patch (7 mg/24 hrs) + prazosin capsule (1 mg)
Spatial Attentional Resource Allocation Task reaction time
average reaction time of trials with a signal detection response
Time frame: 5 hrs after patch application (=2.5 hr after ingestion of capsule)
Spatial Attentional Resource Allocation Task omission errors
percentage of trials on which no response was registered
Time frame: 5 hrs after patch application (=2.5 hr after ingestion of capsule)
Rapid Visual Information Processing Task hit rate
percentage of targets detected
Time frame: 5 hrs after patch application (=2.5 hr after ingestion of capsule)
Rapid Visual Information Processing Task reaction time
average reaction time on trials with a correct response
Time frame: 5 hrs after patch application (=2.5 hr after ingestion of capsule)
Change Detection Task accuracy
percentage of correct responses
Time frame: 5 hrs after patch application (=2.5 hr after ingestion of capsule)
Change Detection reaction time
average reaction time across trials
Time frame: 5 hrs after patch application (=2.5 hr after ingestion of capsule)
Blood pressure
mmHg
Time frame: hourly for 8 hours on each test day
Vital signs: heart rate
beats per minute
Time frame: hourly for 8 hours on each test day
No study locations are listed for this record.
Plan to share: No
No publications or documents are linked to this record.
This study is withdrawn, as verified in Aug 2019. You cannot join it, but the record below documents what was studied.
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University of Maryland, Baltimore