Functional Magnetic Resonance Imaging (fMRI) Investigation of Nicotine Withdrawal Symptoms

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00657020
First received: April 2, 2008
Last updated: April 29, 2010
Last verified: October 2009
  Purpose

A single center, evaluator and subject blind, randomized, placebo controlled, two-administration, two-period crossover study conducted in adult smokers. Subjects will attend a screening visit and two treatment visits. Treatment visits will be separated by at least 48 hours (hrs).


Condition Intervention Phase
Smoking
Drug: Placebo
Drug: Nicotine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind
Primary Purpose: Basic Science
Official Title: Simultaneous fMRI/EEG of the 4 mg Nicotine Lozenge in Relief of Cognitive Impairment Associated With Nicotine Withdrawal

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Percent Blood Oxygen-level Dependent (BOLD) Change From Control Condition in Brain Regions of Abstinent Smokers Performing a Rapid Visual Information Processing (RVIP) Task [ Time Frame: approximately 2 hours following dosing ] [ Designated as safety issue: No ]
    Mean percent BOLD signal change calculated as the difference between fMRI images acquired during experimental conditions of interest (i.e., high or low attention) relative to images acquired during a control condition (i.e., visual fixation). For each brain region of interest, one value was calculated for each contrast: (a) high attention vs control and (b) low attention vs. control.


Secondary Outcome Measures:
  • Response Time for Correct Responses During Rapid Visual Information Processing [ Time Frame: approximately 2 hours post dose ] [ Designated as safety issue: No ]
    Rapid Visual Information Processing (RVIP)- Time to correct response. During the RVIP task, subjects were required to respond to consecutive sequences of three odd or three even numbers by pressing the corresponding response button as quickly and accurately as possible. During a control task, subjects were on required to respond to single occurrences of the number "0"

  • Percentage of Correct Responses During RVIP [ Time Frame: Approximately 2 hours post dose ] [ Designated as safety issue: No ]
    Percentage of correct responses

  • Percent Change From Control Condition at Peak Signal as Displayed by Blood Oxygen-level (BOLD)Activation During Divided Attention [ Time Frame: Approximately 2 hours post dose ] [ Designated as safety issue: No ]
    Mean percent BOLD signal change calculated as the difference between fMRI images acquired during experimental conditions of interest (i.e., high or low attention) relative to images acquired during a control condition (i.e., visual fixation). For each brain region of interest, once value was calculated for each contrast: (a) high attention vs control and (b) low attention vs control.

  • Response Time for Correct Responses During the Divided Attention Task [ Time Frame: Approximately 2 hours post dose ] [ Designated as safety issue: No ]
    Time to correct response. The Divided Attention task comprises three conditions. For the sustained visual attention task subjects were required to responde to the letter "s" every time it appeared in a continuous stream of letters on a screen. For the sustained auditory attention task subjects were required to respond to the number "8" everytime in appear in a continuous stream of numbers presented through headphones. For the divided attention task auditory and visual stimuli were simultaneously presented and subjects were asked to respond to occurrences of "s" (visual) and "8" (auditory).

  • Percentage of Correct Responses During the Divided Attention Task [ Time Frame: Approximately 2 hours post dose ] [ Designated as safety issue: No ]
    Percentage of correct responses


Enrollment: 30
Study Start Date: September 2007
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nicotine
4 mg Nicotine lozenge
Drug: Nicotine
4 mg Nicotine lozenge
Other Name: Nicotine
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo

Detailed Description:

The main objective of this study is to use blood oxygen level-dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) in abstinent smokers to directly evaluate the effect of the 4 mg nicotine mint lozenge on brain activation associated with visual attention. The brain depends on a very high flow of blood to cope with its high demands for oxygen and glucose. Changes in the regional distribution of blood flow are coupled to changes in regional neuronal activity (Offenhauser 2005, Ogawa 1990). An increase of blood flow is accompanied by an increase of hemoglobin. BOLD fMRI measurements (the "BOLD" signal) are based on the relative amount of oxygenated-hemoglobin to deoxygenated-hemoglobin in the blood.

The experimental task featured 3 conditions: 1. a highly demanding cognitive/attention task, 2. a simple cognitive/attention task, and 3. simply look at a '+' symbol. During the experiment these conditions are each presented a number of times in an alternating manner while we acquire the images.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age Aged between 18 and 55 years inclusive.
  • Weight and size

    1. Body mass index (BMI) within the range 19.0-32.0 kg/m.
    2. Able to fit comfortably within the MR scanner.
  • Smoking Status

    1. Cigarette smokers that consume their first manufactured cigarette (i.e., not self rolled cigarettes) within 30 min of waking.
    2. Individuals who have smoked regularly for at least a year.
  • General Status

    1. Right handed subjects.
    2. Able to read and write (in English) at a level sufficient to complete study related assessments.
  • Contraception Females of childbearing potential who are, in the opinion of the investigator, practicing a reliable method of contraception.
  • Compliance Understands and is willing, able and likely to comply with all study procedures and restrictions.
  • General Health Good general health with (in the opinion of the examining study doctor) no clinically significant and relevant abnormalities of medical history, physical examination or clinical laboratory test.
  • Consent Demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form.

Exclusion Criteria:

  • Pregnancy Women who are pregnant or who have a positive urine pregnancy test.
  • Breast-feeding Women who are breast-feeding.
  • Disease/Illness

    1. Any clinically significant medical history or abnormality found on physical examination, laboratory assessment or electrocardiogram (ECG) at screening which, in the opinion of the investigator, could interfere with the interpretation of efficacy or safety data or which otherwise would contraindicate participation in a clinical trial.
    2. Current or recent history or presence of a neurological diagnosis (not limited to but including for example, stroke, traumatic brain injury, carotid arterial sclerotic disease, epilepsy, space occupying lesions, multiple sclerosis, Parkinson's disease, vascular dementia, transient ischemic attack, schizophrenia, major depression etc.) that may influence the outcome or analysis of the scan results.
  • Contraindications to MR scanning

    1. Intracranial aneurysm clips (except Sugita).
    2. History of intra-orbital metal fragments that have not been removed by a doctor (as confirmed by orbital X-Ray).
    3. Inner ear implants.
    4. Tattoos with metal containing inks or piercings that can not be removed except those, which, in the opinion of the Investigator, will not interfere with the study procedures or compromise safety.
    5. History of claustrophobia or subject feels unable to lie still on their back for a period of 90 min in the MR scanner.
    6. Presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-MRI questionnaire supported by plain X-Rays where appropriate.
  • Prior/Concomitant Medication

    1. Use of any central nervous system (CNS) active, prescription medication within 14 days of first treatment visit.
    2. Use of any over the counter (OTC) medication within 14 days of each treatment visit except those, which, in the opinion of the Investigator, will not interfere with the study procedures or compromise safety. Paracetamol (up to 2 g) may be taken up to 24 hrs prior to each treatment visit.
    3. Current use of any nicotine replacement therapy.
  • Clinical Study/Experimental Medication

    1. Participation in another clinical study or receipt of an investigational drug within 3 months of the first treatment visit.
    2. Previous participation in this study.
  • Allergy/Intolerance Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients.
  • Substance abuse

    1. History of regular alcohol consumption exceeding an average weekly intake of more than 14 units per week for females, 21 units per week for males, or an average daily intake greater than 2 units for females and 3 units for males.
    2. Past history of drug abuse (i.e. meeting DSM IV [American Psychiatric Association, 1994] or ICD 10 [World Health Organization, 1990] criteria for substance dependence), excluding nicotine, or has tested positive for urine drugs of abuse at the screening or either treatment visit.
  • Alcohol Consumption of any alcoholic beverages within 24 hours of the treatment visits (as indicated by either a positive breath alcohol test or in the opinion of the Investigator).
  • Caffeine Consumption of large quantities of xanthine containing beverages (e.g., coffee, tea, cola, chocolate etc, more than an average of five cups or glasses per day).
  • Personnel An employee of the sponsor or the study site or members of their immediate family.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00657020

Locations
United Kingdom
GSK Investigational Site
London, United Kingdom
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00657020     History of Changes
Other Study ID Numbers: S3250493
Study First Received: April 2, 2008
Results First Received: October 12, 2009
Last Updated: April 29, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
nicotine
replacement
therapy
fMRI/EEG

Additional relevant MeSH terms:
Substance Withdrawal Syndrome
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014