We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Nicotinic Modulation of the Default Network

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: NCT01223404
Recruitment Status : Completed
First Posted : October 19, 2010
Results First Posted : January 25, 2018
Last Update Posted : August 19, 2019
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Britta Hahn, University of Maryland, Baltimore

Brief Summary:
Many disorders where attentional problems are a hallmark, such as Alzheimer's disease and schizophrenia, display abnormal regulation of the so-called default network of resting brain function that maintains internally directed thought when the mind is free to wander. There is indication that nicotine may improve attention by aiding the deactivation of the default network, and this mechanism may be of therapeutic benefit for the above disease states. The current project aims at providing a proof of concept by demonstrating that nicotinic drugs modulate default network function. The nicotinic agonist nicotine is hypothesized to improve attention by facilitating the down-regulation of default network activity, and the nicotinic antagonist mecamylamine is hypothesized to impair attention by impeding the down-regulation of default network activity during attentional task performance.

Condition or disease Intervention/treatment Phase
Magnetic Resonance Imaging Cognition Nicotine Mecamylamine Drug: Placebo Drug: Nicotine Drug: Mecamylamine Not Applicable

Detailed Description:
This study only enrolls healthy non-smokers. Participants perform attention tasks while undergoing functional Magnetic Resonance Imaging on three separate days. Across the three days, three difference conditions are tested in a double-blind manner, in randomized order. In all test sessions, participants receive a skin patch and swallow a capsule. In one session, both are a placebo. In another, the patch is a low-dose nicotine patch, and the capsule is a placebo. In another session, the patch is a placebo and the capsule contains a low dose of mecamylamine.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Only the statistician performing the randomization and the pharmacist dispensing the drugs were aware which drug was given on which day.
Primary Purpose: Basic Science
Official Title: Nicotinic Modulation of the Default Network of Resting Brain Function
Actual Study Start Date : October 2010
Actual Primary Completion Date : September 2013
Actual Study Completion Date : September 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Placebo, Nicotine, Mecamylamine

Participants undergo 3 test sessions:

In the first session ("placebo"), a placebo patch and a placebo capsule is administered.

In the second session ("nicotine"), a nicotine patch (7 mg/24 hrs) and a placebo capsule is administered.

In the third session ("mecamylamine"), a placebo patch and a mecamylamine capsule is administered.

Drug: Placebo
Participants are administered a placebo patch and a placebo capsule

Drug: Nicotine
Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule
Other Name: Nicotine CQ

Drug: Mecamylamine
Participants are administered a placebo patch and a capsule containing 7.5 mg of mecamylamine

Experimental: Nicotine, Placebo, Mecamylamine

Participants undergo 3 test sessions:

In the first session ("nicotine"), a nicotine patch and a placebo capsule is administered.

In the second session ("placebo"), a placebo patch (7 mg/24 hrs) and a placebo capsule is administered.

In the third session ("mecamylamine"), a placebo patch and a mecamylamine capsule is administered.

Drug: Placebo
Participants are administered a placebo patch and a placebo capsule

Drug: Nicotine
Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule
Other Name: Nicotine CQ

Drug: Mecamylamine
Participants are administered a placebo patch and a capsule containing 7.5 mg of mecamylamine

Experimental: Placebo, Mecamylamine, Nicotine

Participants undergo 3 test sessions:

In the first session ("placebo"), a placebo patch and a placebo capsule is administered.

In the second session ("mecamylamine"), a placebo patch (7 mg/24 hrs) and a mecamylamine capsule is administered.

In the third session ("nicotine"), a nicotine patch and a placebo capsule is administered.

Drug: Placebo
Participants are administered a placebo patch and a placebo capsule

Drug: Nicotine
Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule
Other Name: Nicotine CQ

Drug: Mecamylamine
Participants are administered a placebo patch and a capsule containing 7.5 mg of mecamylamine

Experimental: Nicotine, Mecamylamine, Placebo

Participants undergo 3 test sessions:

In the first session ("nicotine"), a nicotine patch and a placebo capsule is administered.

In the second session ("mecamylamine"), a placebo patch (7 mg/24 hrs) and a mecamylamine capsule is administered.

In the third session ("placebo"), a placebo patch and a placebo capsule is administered.

Drug: Placebo
Participants are administered a placebo patch and a placebo capsule

Drug: Nicotine
Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule
Other Name: Nicotine CQ

Drug: Mecamylamine
Participants are administered a placebo patch and a capsule containing 7.5 mg of mecamylamine

Experimental: Mecamylamine, Placebo, Nicotine

Participants undergo 3 test sessions:

In the first session ("mecamylamine"), a placebo patch and a mecamylamine capsule is administered.

In the second session ("placebo"), a placebo patch (7 mg/24 hrs) and a placebo capsule is administered.

In the third session ("nicotine"), a nicotine patch and a placebo capsule is administered.

Drug: Placebo
Participants are administered a placebo patch and a placebo capsule

Drug: Nicotine
Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule
Other Name: Nicotine CQ

Drug: Mecamylamine
Participants are administered a placebo patch and a capsule containing 7.5 mg of mecamylamine

Experimental: Mecamylamine, Nicotine, Placebo

Participants undergo 3 test sessions:

In the first session ("mecamylamine"), a placebo patch and a mecamylamine capsule is administered.

In the second session ("nicotine"), a nicotine patch (7 mg/24 hrs) and a placebo capsule is administered.

In the third session ("placebo"), a placebo patch and a placebo capsule is administered.

Drug: Placebo
Participants are administered a placebo patch and a placebo capsule

Drug: Nicotine
Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule
Other Name: Nicotine CQ

Drug: Mecamylamine
Participants are administered a placebo patch and a capsule containing 7.5 mg of mecamylamine




Primary Outcome Measures :
  1. Reaction Time [ Time Frame: 1 day ]
    average reaction time on cognitive task performed in the MR scanner

  2. Signal Detection Performance [ Time Frame: 1 day ]
    Signal detection on cognitive tasks performed in the MR scanner. For the attention task, this represents the percentage of trials in which the participant responded when a signal was presented. In the working memory task (N-back task), this represents the percentage of all target sequences to which the participant responded.

  3. Default Network Activity [ Time Frame: 1 day ]
    Cognitive task-induced default network deactivation, measured by functional Magnetic Resonance Imaging. The default network was probed by five pre-defined ROIs per hemisphere. Task-induced deactivation was averaged across all ROIs.


Secondary Outcome Measures :
  1. Subjective State [ Time Frame: 1 day ]
    End-of-session subjective state is measured by the Profile of Mood States (POMS). We utilize "Total Mood Disturbance" (TMD) as a summary measure, derived by adding the total scores on the five negative mood scales (tension, depression, anger, fatigue, confusion) and subtracting the score on the one positive mood scale (vigor). The theoretical range of the TMD scale is -32 to 228, with negative values indicating less mood disturbance, i.e., a more positive emotional state.

  2. Systolic Blood Pressure [ Time Frame: Bi-hourly: prior to patch application, 2 hours, 4 hours, and 6 hours after, and after the MRI scan (~8 hours after patch application) ]
    Systolic blood pressure (mmHg)

  3. Diastolic Blood Pressure [ Time Frame: Bi-hourly: prior to patch application, 2 hours, 4 hours, and 6 hours after, and after the MRI scan (~8 hours after patch application). ]
    Diastolic blood pressure in mmHg.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 21 through 50.
  • Did not consume cigarettes, cigarillos, cigars, or other tobacco or nicotine-containing products more than 20 times in lifetime, and did not use any nicotine-containing product at all within the last two years.
  • Normal or corrected to normal vision (at least 20/80).

Exclusion Criteria:

  • Presence of metal objects in the body, implanted electronic devices, or any other counter indication for MRI.
  • Claustrophobia.
  • Major psychiatric disorders including mood, anxiety or psychotic disorders.
  • Cardiovascular or cerebrovascular disease, such as history of myocardial infarction, heart failure, angina, stroke, severe arrhythmias, or EKG abnormalities.
  • Kidney or liver disease.
  • Hypertension (resting systolic BP above 140 or diastolic above 85 mm Hg).
  • Hypotension (resting systolic BP below 95 or diastolic below 60).
  • Use of any prescription or over-the-counter drug other than supplements and birth control.
  • History of or current neurological illnesses, such as stroke, seizures, dementia or organic brain syndrome.
  • Learning disability, attention deficit disorder, or any other condition that impedes memory and attention.
  • Glaucoma, organic pyloric stenosis, uremia or renal insufficiency.
  • Prostatic hypertrophy, bladder neck obstruction or urethral stricture.
  • Left-handed or ambidextrous.
  • Pregnant as determined by urine test, or breast-feeding.
  • History or current diagnosis of drug or alcohol abuse or dependence.
  • IQ < 85 as estimated by the WASI vocabulary subtest.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01223404


Locations
Layout table for location information
United States, Maryland
National Institute on Drug Abuse, Intramural Research Program
Baltimore, Maryland, United States, 21224
Maryland Psychiatric Research Center
Baltimore, Maryland, United States, 21228
Sponsors and Collaborators
University of Maryland, Baltimore
National Institute on Drug Abuse (NIDA)
Investigators
Layout table for investigator information
Principal Investigator: Britta Hahn, Ph.D. University of Maryland, College Park
Publications:
Layout table for additonal information
Responsible Party: Britta Hahn, Associate Professor, University of Maryland, Baltimore
ClinicalTrials.gov Identifier: NCT01223404    
Other Study ID Numbers: HP-00042696
R21DA027894 ( U.S. NIH Grant/Contract )
First Posted: October 19, 2010    Key Record Dates
Results First Posted: January 25, 2018
Last Update Posted: August 19, 2019
Last Verified: August 2019
Keywords provided by Britta Hahn, University of Maryland, Baltimore:
nicotine
mecamylamine
attention
default network
fMRI
Additional relevant MeSH terms:
Layout table for MeSH terms
Mecamylamine
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
Ganglionic Blockers
Nicotinic Antagonists
Cholinergic Antagonists