Nicotinic Modulation of the Default Network of Resting Brain Function
Background:
- A brain circuit called the default network is the brain circuit that is active when the brain is at rest; that is, when individuals are not concentrating on specific tasks. Previous research has shown that the default network functions differently in people with schizophrenia and Alzheimer s disease, and may contribute to the problems with memory and concentration that can affect people who have these conditions. Studies have also shown that nicotine affects the default network, but more research is needed on the ways in which nicotinic receptors may change activity in these regions and thereby affect individuals ability to concentrate on specific tasks.
Objectives:
- To determine whether and how nicotine and mecamylamine, a drug that blocks nicotinic receptors, affect the default network in nonsmokers in ways that improve thinking and concentration.
Eligibility:
- Healthy, right-handed volunteers between 21 and 50 years of age.
- Volunteers must not have used any kind of tobacco product in the past 2 years.
Design:
- This study involves an initial screening visit, a training visit, and three testing visits.
- Participants will be screened with a medical history and physical examination, as well as blood and urine samples and questions about smoking history.
- Participants will have an initial training session to practice the tasks that will be done during magnetic resonance imaging scans at the testing visits. These tasks will test participants concentration and memory.
- Participants will have three test sessions with the following combinations of study drugs: (1) a nicotine patch and a placebo capsule, (2) a placebo patch and a capsule of mecamylamine, or (3) a placebo patch and capsule. Different combinations will be given at each visit, and participants will not know which one they receive.
- Participants will perform the same concentration and memory tasks at each testing visit, and will provide a blood sample after each visit to determine levels of nicotine and mecamylamine.
연구 개요
상태
상태
정황
정황
상세 설명
Objective: To evaluate the potential of manipulating activity in the so-called default network of resting brain function by nicotinic ligands. Default network activity modulates cognitive functioning, and effects of nicotine thereon may motivate smoking behavior. In the future, this mechanism could become a novel approach to improving cognition in disease populations that show dysfunction of this network, such as schizophrenia or Alzheimer s disease.
Study population: 27 healthy non-smokers.
Design: A double-blind, placebo-controlled, within-subject fMRI study, evaluating regional brain activation and cognitive functions under conditions of transdermal nicotine (7 mg/day), oral mecamylamine (a nicotinic antagonist, 7.5 mg), and placebo.
Outcome measures: Activity and functional connectivity of default regions during cognitive task performance, measures of cognitive task performance, measures of subjective state, and plasma concentrations of nicotine, nicotine metabolites and mecamylamine.
연구 유형
연구 유형
등록 (실제)
등록
연락처 및 위치
연구 장소
-
-
Maryland
-
Baltimore, Maryland, 미국, 21224
- National Institute on Drug Abuse, Biomedical Research Center (BRC)
-
Catonsville, Maryland, 미국, 21228
- University of Maryland at Baltimore/MPRC
-
-
참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
INCLUSION CRITERIA:
- Age 21 through 55. We want to avoid exposing a maturing brain to centrally active substances that it has not previously been exposed to (non-smokers), and to increase sensitivity for measuring drug effects by minimizing population inhomogeneity related to both cognitive decline with normal aging (Verhaeghen and Salthouse 1997, De Luca et al. 2003) and to ongoing brain maturation.
- 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 as specified under Screening methods .
- 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 (see Mecamylamine-related risks).
- Prostatic hypertrophy, bladder neck obstruction or urethral stricture (see Mecamylamine-related risks).
- 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.
- Strong disposition to get car sick.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
|---|
|
Activity and functional connectivity of default regions during cognitive task performance, measures of cognitive task performance, measures of subjective state, and plasma concentrations of nicotine, nicotine metabolites and mecamylamine.
|
공동 작업자 및 조사자
간행물 및 유용한 링크
일반 간행물
- Binder JR, Frost JA, Hammeke TA, Bellgowan PS, Rao SM, Cox RW. Conceptual processing during the conscious resting state. A functional MRI study. J Cogn Neurosci. 1999 Jan;11(1):80-95. doi: 10.1162/089892999563265.
- Bluhm RL, Miller J, Lanius RA, Osuch EA, Boksman K, Neufeld RW, Theberge J, Schaefer B, Williamson P. Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network. Schizophr Bull. 2007 Jul;33(4):1004-12. doi: 10.1093/schbul/sbm052. Epub 2007 Jun 7.
- Boyajian RA, Otis SM. Acute effects of smoking on human cerebral blood flow: a transcranial Doppler ultrasonography study. J Neuroimaging. 2000 Oct;10(4):204-8. doi: 10.1111/jon2000104204.
연구 기록 날짜
연구 주요 날짜
연구 시작
연구 시작
연구 완료
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .