Nicotinic Modulation of the Default Network of Resting Brain Function
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Reaction Time
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Only the statistician performing the randomization and the pharmacist dispensing the drugs were aware which drug was given on which day.
入排标准
- 年龄范围
- 21 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 21 through
- •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).
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Placebo (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Mecamylamine (Drug)
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.
干预措施: Mecamylamine (Drug)
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.
干预措施: Nicotine (Drug)
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.
干预措施: Nicotine (Drug)
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.
干预措施: Mecamylamine (Drug)
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.
干预措施: Mecamylamine (Drug)
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.
干预措施: Nicotine (Drug)
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.
干预措施: Nicotine (Drug)
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.
干预措施: Mecamylamine (Drug)
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.
干预措施: Nicotine (Drug)
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.
干预措施: Nicotine (Drug)
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.
干预措施: Mecamylamine (Drug)
结局指标
主要结局
Reaction Time
时间窗: 1 day
average reaction time on cognitive task performed in the MR scanner
Signal Detection Performance
时间窗: 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.
Default Network Activity
时间窗: 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.
次要结局
- Subjective State(1 day)
- 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).)
- 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))
研究者
Britta Hahn
Associate Professor
University of Maryland, Baltimore