Functional Magnetic Resonance Imaging (fMRI) Investigation of Nicotine Withdrawal Symptoms
Condition: Smoking
Intervention: Nicotine; Placebo
Intervention description: Nicotine lozenge containing 4 mg of nicotine; Placebo lozenge
Intervention MeSH terms: Nicotine
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: nicotine; therapy; fMRI/EEG; replacement

Summary:

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

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).