Nicotinic Modulation of the Default Network

NCT ID: NCT01223404

Last Updated: 2019-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2013-09-30

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.

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

Magnetic Resonance Imaging; Cognition; Nicotine; Mecamylamine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Participants are administered a placebo patch and a placebo capsule

Nicotine

Intervention Type: DRUG

Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule

Mecamylamine

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Participants are administered a placebo patch and a placebo capsule

Nicotine

Intervention Type: DRUG

Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule

Mecamylamine

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Participants are administered a placebo patch and a placebo capsule

Nicotine

Intervention Type: DRUG

Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule

Mecamylamine

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Participants are administered a placebo patch and a placebo capsule

Nicotine

Intervention Type: DRUG

Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule

Mecamylamine

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Participants are administered a placebo patch and a placebo capsule

Nicotine

Intervention Type: DRUG

Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule

Mecamylamine

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Participants are administered a placebo patch and a placebo capsule

Nicotine

Intervention Type: DRUG

Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule

Mecamylamine

Intervention Type: DRUG

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

Interventions

Placebo

Participants are administered a placebo patch and a placebo capsule

Intervention Type: DRUG

Nicotine

Participants are administered a nicotine patch (7 mg/24 hrs) and a placebo capsule

Intervention Type: DRUG

Mecamylamine

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

Intervention Type: DRUG

Other Intervention Names

Nicotine CQ

Eligibility 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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Britta Hahn

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Britta Hahn, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, College Park

Locations

National Institute on Drug Abuse, Intramural Research Program

Baltimore, Maryland, United States

Maryland Psychiatric Research Center

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 17392464 (View on PubMed)

Other Identifiers

R21DA027894

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HP-00042696

Identifier Type: -

Identifier Source: org_study_id