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Effects of Prazosin on the Attention-Enhancing Effects of Nicotine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03416569
Recruitment Status : Withdrawn (Unanticipated staff changes are preventing completion within funding period.)
First Posted : January 31, 2018
Last Update Posted : August 19, 2019
Sponsor:
Information provided by (Responsible Party):
Britta Hahn, University of Maryland, Baltimore

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
no Condition, Basic Science Drug: Placebo Drug: Nicotine Drug: Prazosin Drug: Nicotine + Prazosin Not Applicable

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Each participant is tested with each of four test conditions, in counterbalanced sequence.
Masking: None (Open Label)
Masking Description: The study will be double-blind. Only the statistician performing randomization and the dispensing pharmacist will know the sequence of test conditions.
Primary Purpose: Basic Science
Official Title: The Effects of Prazosin on the Attention-Enhancing Effects of Nicotine in Healthy Non-Smokers
Estimated Study Start Date : March 2018
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nicotine-Prazosin Interaction Study
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
placebo skin patch + placebo capsule

Drug: Nicotine
nicotine patch (7 mg/24 hrs) + placebo capsule

Drug: Prazosin
placebo patch (7 mg/24 hrs) + prazosin capsule (1 mg)

Drug: Nicotine + Prazosin
nicotine patch (7 mg/24 hrs) + prazosin capsule (1 mg)




Primary Outcome Measures :
  1. Spatial Attentional Resource Allocation Task reaction time [ Time Frame: 5 hrs after patch application (=2.5 hr after ingestion of capsule) ]
    average reaction time of trials with a signal detection response

  2. Spatial Attentional Resource Allocation Task omission errors [ Time Frame: 5 hrs after patch application (=2.5 hr after ingestion of capsule) ]
    percentage of trials on which no response was registered

  3. Rapid Visual Information Processing Task hit rate [ Time Frame: 5 hrs after patch application (=2.5 hr after ingestion of capsule) ]
    percentage of targets detected

  4. Rapid Visual Information Processing Task reaction time [ Time Frame: 5 hrs after patch application (=2.5 hr after ingestion of capsule) ]
    average reaction time on trials with a correct response

  5. Change Detection Task accuracy [ Time Frame: 5 hrs after patch application (=2.5 hr after ingestion of capsule) ]
    percentage of correct responses

  6. Change Detection reaction time [ Time Frame: 5 hrs after patch application (=2.5 hr after ingestion of capsule) ]
    average reaction time across trials


Secondary Outcome Measures :
  1. Blood pressure [ Time Frame: hourly for 8 hours on each test day ]
    mmHg

  2. Vital signs: heart rate [ Time Frame: hourly for 8 hours on each test day ]
    beats per minute



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aged 21 to 55 years.
  • Smoked no more that 40 cigarettes, cigars or cigarillos in lifetime.
  • Smoked no cigarettes, cigars or cigarillos in the last year.
  • No exposure to any nicotine-containing product in the last month.
  • Normal or corrected to normal vision (at least 20/80).

Exclusion Criteria:

  • Pregnant or breast-feeding.
  • Drug or alcohol abuse or dependence currently or in the last 2 years.
  • DSM Axis I mood, anxiety or psychotic disorder.
  • Cardiovascular or cerebrovascular disease.
  • Hypertension (resting systolic BP above 150 or diastolic above 95 mm Hg).
  • Hypotension (resting systolic BP below 90 or diastolic below 60).
  • Bradycardia (heart rate <60 bpm).
  • Impaired liver or kidney function.
  • Severe asthma.
  • Obstructive pulmonary disease.
  • Type I diabetes.
  • Use of any centrally active medications.
  • Use of any cardiovascular drugs, including blood pressure medications and antiarrhythmics.
  • Use of diuretic medication.
  • History of or current neurological illnesses, such as stroke, seizure disorders, neurodegenerative diseases, or organic brain syndrome.
  • Learning disability, mental retardation, or any other condition that impedes cognition.
  • Planned eye surgery.
  • Inability to perform the Rapid Visual Information Processing Task.
  • Known hypersensitivity to prazosin, any quinazolines, or nicotine.
  • Narcolepsy.
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Responsible Party: Britta Hahn, Associate Professor, University of Maryland, Baltimore
ClinicalTrials.gov Identifier: NCT03416569    
Other Study ID Numbers: HP-00078832
First Posted: January 31, 2018    Key Record Dates
Last Update Posted: August 19, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Prazosin
Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents