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Completed

NCT Number: NCT01223404

Nicotinic Modulation of the Default Network

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.

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Key information

Age range

21 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Maryland Psychiatric Research Center, Baltimore, Maryland, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Placebo

Drug

Participants are administered a placebo patch and a placebo capsule

nicotine

Drug

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

Other names: Nicotine CQ

mecamylamine

Drug

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

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

University of Maryland, Baltimore

Other

Collaborators

  • National Institute on Drug Abuse (NIDA)

Registry information

Official study title

Nicotinic Modulation of the Default Network of Resting Brain Function

Important dates

Study start
2010
Primary completion
2013
Study completion
2013
First posted
Oct 19, 2010
Registry last updated
Aug 19, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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