Nicotinic Modulation of the Default Network

NCT01223404 | Completed Results DMC

• 2 other identifiers: HP-00042696R21DA027894
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

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.

Conditions

Magnetic Resonance Imaging; Cognition; Nicotine; Mecamylamine

Keywords

nicotine; mecamylamine; attention; default network; fMRI

Outcome Measures

Primary Outcomes (3)

• Reaction Time

  average reaction time on cognitive task performed in the MR scanner

  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.

  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.

  1 day

Secondary Outcomes (3)

• Subjective State

  1 day

• Systolic Blood Pressure

  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

  Bi-hourly: prior to patch application, 2 hours, 4 hours, and 6 hours after, and after the MRI scan (~8 hours after patch application).

Study Arms (6)

Placebo, Nicotine, Mecamylamine

EXPERIMENTAL

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

Nicotine, Placebo, Mecamylamine

EXPERIMENTAL

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

Placebo, Mecamylamine, Nicotine

EXPERIMENTAL

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

Nicotine, Mecamylamine, Placebo

EXPERIMENTAL

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

Mecamylamine, Placebo, Nicotine

EXPERIMENTAL

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

Mecamylamine, Nicotine, Placebo

EXPERIMENTAL

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

Placebo DRUG

Participants are administered a placebo patch and a placebo capsule

Mecamylamine, Nicotine, Placebo; Mecamylamine, Placebo, Nicotine; Nicotine, Mecamylamine, Placebo; Nicotine, Placebo, Mecamylamine; Placebo, Mecamylamine, Nicotine; Placebo, Nicotine, Mecamylamine

Nicotine DRUG

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

Also known as: Nicotine CQ

Mecamylamine, Nicotine, Placebo; Mecamylamine, Placebo, Nicotine; Nicotine, Mecamylamine, Placebo; Nicotine, Placebo, Mecamylamine; Placebo, Mecamylamine, Nicotine; Placebo, Nicotine, Mecamylamine

Mecamylamine DRUG

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

Mecamylamine, Nicotine, Placebo; Mecamylamine, Placebo, Nicotine; Nicotine, Mecamylamine, Placebo; Nicotine, Placebo, Mecamylamine; Placebo, Mecamylamine, Nicotine; Placebo, Nicotine, Mecamylamine

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (2)

National Institute on Drug Abuse, Intramural Research Program

Baltimore, Maryland, 21224, United States

Location

Maryland Psychiatric Research Center

Baltimore, Maryland, 21228, United States

Location

Related Publications (1)

• 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.

  PMID: 17392464 BACKGROUND

MeSH Terms

Interventions

Nicotine; Mecamylamine

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Norbornanes; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Britta Hahn
• Organization: University of Maryland School of Medicine

bhahn@mprc.umaryland.edu

4104026112

Study Officials

• Britta Hahn, Ph.D.

  University of Maryland, College Park

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only the statistician performing the randomization and the pharmacist dispensing the drugs were aware which drug was given on which day.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 13, 2010
• First Posted: October 19, 2010
• Study Start: October 1, 2010
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: August 19, 2019
• Results First Posted: January 25, 2018

Record last verified: 2019-08

Locations

US (2)