Clinical trial NCT00657020: Functional Magnetic Resonance Imaging (fMRI) Investigation of Nicotine Withdrawal Symptoms
Official title: Simultaneous fMRI/EEG of the 4 mg Nicotine Lozenge in Relief of Cognitive Impairment Associated With Nicotine Withdrawal
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Smoking
Keywords: nicotine
therapy
fMRI/EEG
replacement
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-04-14
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: A single center, double blind, randomized, placebo controlled, two-treatments, two-period crossover study conducted in adult smokers.

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 milligrams (mg) nicotine lozenge on brain activation associated with visual attention. 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 acquiring images.

Eligibility criteria: Inclusion Criteria:

* 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.
* Females of childbearing potential who are, in the opinion of the investigator, practicing a reliable method of contraception.
* Understands and is willing, able and likely to comply with all study procedures and restrictions.
* 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.
* 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:

* Women who are pregnant or who have a positive urine pregnancy test or
* 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
  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.
* 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, excluding nicotine, or has tested positive for urine drugs of abuse at the screening or either treatment visit.
* 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).
* 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).

Primary outcomes:
measure: Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task
timeFrame: Approximately 2 hours post dose administration
Secondary outcomes:
measure: Mean Response Time for Correct Responses During RVIP Task
timeFrame: Approximately 2 hours post dose administration
measure: Mean Percentage of Correct Responses During RVIP Task
timeFrame: Approximately 2 hours post dose administration
measure: Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task
timeFrame: Approximately 2 hours post dose admininstration
measure: Mean Response Time for Correct Responses During DIA Task
timeFrame: Approximately 2 hours post dose administration
measure: Mean Percentage of Correct Responses During DIA Task
timeFrame: Approximately 2 hours post dose administration
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: