CompletedNCT01223404Updated Aug 19, 2019Results posted

Nicotinic Modulation of the Default Network

An interventional study of Placebo and Nicotine in Magnetic Resonance Imaging, Cognition and Nicotine, sponsored by University of Maryland, Baltimore. Completed at 2 sites in United States. Open to participants aged 21 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-08-19.

Sponsored by University of Maryland, Baltimore · Not applicable, Interventional, and Basic science

Phase: Not applicable
Study type: Interventional
Enrollment: 21
Allocation: Randomized
Ages: 21 Years to 50 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Magnetic Resonance Imaging
Cognition
Nicotine
Mecamylamine

Keywords

nicotine
mecamylamine
attention
default network
fMRI

In context

Lead sponsor

University of Maryland, Baltimore is the lead sponsor of 687 studies on the registry; 130 are open to participants now.

Of its 90 completed or terminated interventional studies of FDA-regulated products, 63 (70%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 21 Years to 50 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

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

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.

Study design

Phase: Not applicable
Primary purpose: Basic science
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Triple (Participant, Investigator, Outcomes assessor)
Enrollment: 21 participants (actual)

Study arms

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 · Drug: Nicotine · Drug: 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 · Drug: Nicotine · Drug: 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 · Drug: Nicotine · Drug: 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 · Drug: Nicotine · Drug: 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 · Drug: Nicotine · Drug: 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 · Drug: Nicotine · Drug: Mecamylamine

Interventions

DrugPlacebo
Participants are administered a placebo patch and a placebo capsule
DrugNicotine
Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule
Also known as: Nicotine CQ
DrugMecamylamine
Participants are administered a placebo patch and a capsule containing 7.5 mg of mecamylamine

What researchers measure

Primary outcomes

Reaction Time
average reaction time on cognitive task performed in the MR scanner
Time frame: 1 day
Signal Detection Performance
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.
Time frame: 1 day
Default Network Activity
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.
Time frame: 1 day

Secondary outcomes

Subjective State
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.
Time frame: 1 day
Systolic Blood Pressure
Systolic blood pressure (mmHg)
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
Diastolic blood pressure in mmHg.
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).

Results

Posted Jan 25, 2018

Participant flow

First Intervention (1 Day)

Participant flow — First Intervention (1 Day)
Milestone	Placebo, Nicotine, Mecamylamine	Nicotine, Placebo, Mecamylamine	Placebo, Mecamylamine, Nicotine	Nicotine, Mecamylamine, Placebo	Mecamylamine, Placebo, Nicotine	Mecamylamine, Nicotine, Placebo
Started	4	3	4	5	2	3
Completed	4	3	4	4	2	3
Not completed	0	0	0	1	0	0
Withdrew: Adverse event	0	0	0	1	0	0

Second Intervention (1 Day)

Participant flow — Second Intervention (1 Day)
Milestone	Placebo, Nicotine, Mecamylamine	Nicotine, Placebo, Mecamylamine	Placebo, Mecamylamine, Nicotine	Nicotine, Mecamylamine, Placebo	Mecamylamine, Placebo, Nicotine	Mecamylamine, Nicotine, Placebo
Started	4	3	4	4	2	3
Completed	3	3	4	4	2	3
Not completed	1	0	0	0	0	0
Withdrew: Adverse event	1	0	0	0	0	0

Third Intervention (1 Day)

Participant flow — Third Intervention (1 Day)
Milestone	Placebo, Nicotine, Mecamylamine	Nicotine, Placebo, Mecamylamine	Placebo, Mecamylamine, Nicotine	Nicotine, Mecamylamine, Placebo	Mecamylamine, Placebo, Nicotine	Mecamylamine, Nicotine, Placebo
Started	3	3	4	4	2	3
Completed	3	3	4	3	2	3
Not completed	0	0	0	1	0	0
Withdrew: Non-compliance (slept)	0	0	0	1	0	0

Outcome measures

PrimaryReaction Time

average reaction time on cognitive task performed in the MR scanner

Time frame:: 1 day
Reported as:: Mean · ms

Reaction Time
ms	Intervention: Placebo	Intervention: Nicotine	Intervention: Mecamylamine
Attention task reaction time	512 (485 to 539)	492 (464 to 520)	524 (489 to 559)
Working memory task reaction time	541 (516 to 566)	533 (508 to 558)	573 (537 to 609)

PrimarySignal Detection Performance

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.

Time frame:: 1 day
Reported as:: Mean · percentage of all targets

Signal Detection Performance
percentage of all targets	Intervention: Placebo	Intervention: Nicotine	Intervention: Mecamylamine
Attention task correct identifications	86.4 (81.4 to 91.4)	93.8 (90.1 to 97.5)	85.2 (79.7 to 90.7)
Working memory task correct detections	89.6 (88.4 to 90.8)	95.5 (94.9 to 96.1)	88.6 (87.9 to 89.3)

PrimaryDefault Network Activity

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.

Time frame:: 1 day
Reported as:: Mean · percentage of task-induced signal change

Default Network Activity
percentage of task-induced signal change	Intervention: Placebo	Intervention: Nicotine	Intervention: Mecamylamine
Default Network Activity	-0.29 (-0.41 to -0.17)	-0.24 (-0.39 to -0.09)	-0.21 (-0.33 to -0.09)

SecondarySubjective State

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.

Time frame:: 1 day
Reported as:: Mean · units on a scale

Subjective State
units on a scale	Intervention: Placebo	Intervention: Nicotine	Intervention: Mecamylamine
Subjective State	-6.7 (-12.3 to -1.1)	-9.9 (-15.4 to -4.4)	-5.8 (-12 to 0.4)

SecondarySystolic Blood Pressure

Systolic blood pressure (mmHg)

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)
Reported as:: Mean · mmHG

Systolic Blood Pressure
mmHG	Intervention: Placebo	Intervention: Nicotine	Intervention: Mecamylamine
Pre-patch	120.2 ± 11.4	120.9 ± 16.7	119.3 ± 14.8
2 hours post patch	116.1 ± 11.9	114.3 ± 10.7	112.3 ± 8.6
4 hours post patch	120.1 ± 16.7	119.1 ± 9.9	114.4 ± 11.4
6 hours post patch	120.3 ± 12.9	122.7 ± 12.7	118.2 ± 14.1
Post-scan	129.7 ± 16.1	127.4 ± 9.8	121.5 ± 13.8

SecondaryDiastolic Blood Pressure

Diastolic blood pressure in mmHg.

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).
Reported as:: Mean · mmHG

Diastolic Blood Pressure
mmHG	Intervention: Placebo	Intervention: Nicotine	Intervention: Mecamylamine
Pre-patch	74.4 ± 8.0	71.6 ± 10.0	73.4 ± 10.1
2 hours post patch	73.4 ± 10.0	71.9 ± 9.9	73.2 ± 9.7
4 hours post patch	73.7 ± 9.7	71.1 ± 7.9	72.4 ± 6.9
6 hours post patch	75.8 ± 6.6	75.3 ± 5.8	75.2 ± 8.1
Post-scan	81.3 ± 5.4	81.1 ± 5.7	79.6 ± 9.4

Adverse events

Collected over 1 day (on each of separate 3 test days). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Intervention: Placebo	0/20 (0%)	0/20 (0%)	0/20 (0%)
Intervention: Nicotine	0/21 (0%)	0/21 (0%)	2/21 (9.5%)
Intervention: Mecamylamine	0/19 (0%)	0/19 (0%)	0/19 (0%)

Most frequent other events

Most frequent other events
Event	Intervention: Placebo	Intervention: Nicotine	Intervention: Mecamylamine
VomitingGastrointestinal disorders	0/20	2/21	0/19

Baseline characteristics

21 healthy non-smokers were randomized.

Age, Categorical
Age, Categorical(Participants)	All Study Participants
<=18 years	0
Between 18 and 65 years	21
>=65 years	0

Sex: Female, Male
Sex: Female, Male(Participants)	All Study Participants
Female	9
Male	12

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	All Study Participants
American Indian or Alaska Native	0
Asian	1
Native Hawaiian or Other Pacific Islander	0
Black or African American	13
White	7
More than one race	0
Unknown or Not Reported	0

Region of Enrollment
Region of Enrollment(participants)	All Study Participants
United States	21

Study locations

2 sites

National Institute on Drug Abuse, Intramural Research Program
Baltimore, Maryland 21224, United States
Maryland Psychiatric Research Center
Baltimore, Maryland 21228, United States

References and documents

Publications

Hahn B, Ross TJ, Yang Y, Kim I, Huestis MA, Stein EA. Nicotine enhances visuospatial attention by deactivating areas of the resting brain default network. J Neurosci. 2007 Mar 28;27(13):3477-89. doi: 10.1523/JNEUROSCI.5129-06.2007. PubMed 17392464 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 19, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01223404
Lead sponsor: University of Maryland, Baltimore
Collaborators: National Institute on Drug Abuse (NIDA)
Responsible party: Britta Hahn (Associate Professor, University of Maryland, Baltimore) — Principal investigator
First posted: Oct 19, 2010
Start date: Oct 2010
Primary completion: Sep 2013
Completion: Sep 2013
Results posted: Jan 25, 2018
Last update: Aug 19, 2019

Study contacts

Britta Hahn, Ph.D.

principal investigator · University of Maryland, College Park

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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