Smoking
Conditions
Keywords
nicotine, therapy, fMRI/EEG, replacement
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.
Interventions
DRUGNicotine
Nicotine lozenge containing 4 mg of nicotine
DRUGPlacebo
Placebo lozenge
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | Approximately 2 hours post dose administration | In RVIP task, participant responded 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, participant responded to single occurrences of the number 0. BOLD fMRI signals evaluated different brain regions of interest (ROI) during RVIP task. Brain ROIs identified were right and left anterior insula, anterior putamen, parietal cortex, premotor cortex, visual cortex, dorsal anterior cingulate cortex, substantia nigra and thalamus. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Response Time for Correct Responses During RVIP Task | Approximately 2 hours post dose administration | During the RVIP task, participants responded 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, participants responded to single occurrences of the number 0. Mean response time for correct responses was determined. |
| Mean Percentage of Correct Responses During RVIP Task | Approximately 2 hours post dose administration | Percentage of correct responses during RVIP task was determined |
| Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Approximately 2 hours post dose admininstration | BOLD fMRI signals evaluated different brain ROIs during DIA task which comprised of three conditions: i) Sustained visual attention wherein participant responded to letter s every time it appeared in a continuous stream of letters on a screen; ii) Sustained auditory attention wherein participant responded to the number 8 each time in appeared in a continuous stream of numbers presented through headphones; iii) Divided attention task auditory and visual stimuli wherein participant responded to occurrences of s (visual) and 8 (auditory) simultaneously. Brain ROIs were right and left parietal cortex, visual cortex, superior occipital cortex and right premotor cortex. |
| Mean Response Time for Correct Responses During DIA Task | Approximately 2 hours post dose administration | DIA task comprised of three conditions: i) Sustained visual attention wherein participant responded to letter s every time it appeared in a continuous stream of letters on a screen; ii) Sustained auditory attention wherein participant responded to the number 8 each time in appeared in a continuous stream of numbers presented through headphones; iii) Divided attention task auditory and visual stimuli wherein participant responded to occurrences of s (visual) and 8 (auditory) simultaneously. Mean response time for correct responses was determined. |
| Mean Percentage of Correct Responses During DIA Task | Approximately 2 hours post dose administration | Mean percentage of correct responses during DIA task was determined. |
Participant flow
Pre-assignment details
A total of 45 participants were screened, 22 were considered screen failures. Investigators identified brain regions showing significant blood oxygen-level dependent (BOLD) activation associated with attention in each participant using Functional Magnetic Resonance Imaging (fMRI). Hence, participants categorized into high/low attention conditions.
Participants by arm
| Arm | Count |
|---|---|
| All Randomized Participants All randomized participants who receive study treatments. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| PERIOD 1 | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | All Randomized Participants |
|---|---|
| Age, Continuous | 30.82 years STANDARD_DEVIATION 8.428 |
| Race/Ethnicity, Customized Caucasian | 23 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 22 | 0 / 23 |
| serious Total, serious adverse events | 0 / 22 | 0 / 23 |
Outcome results
Primary
Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task
In RVIP task, participant responded 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, participant responded to single occurrences of the number 0. BOLD fMRI signals evaluated different brain regions of interest (ROI) during RVIP task. Brain ROIs identified were right and left anterior insula, anterior putamen, parietal cortex, premotor cortex, visual cortex, dorsal anterior cingulate cortex, substantia nigra and thalamus.
Time frame: Approximately 2 hours post dose administration
Population: Number of participants with complete imaging data on both treatments (nicotine and placebo).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Dorsolateral Pre-Frontal Cortex | 0.0 Percentage change in BOLD signal | Standard Deviation 0.29 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Anterior Insula | 0.0 Percentage change in BOLD signal | Standard Deviation 0.21 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Anterior Putamen | 0.0 Percentage change in BOLD signal | Standard Deviation 0.2 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Dorsal Anterior Cingulate Cortex | 0.3 Percentage change in BOLD signal | Standard Deviation 0.39 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Parietal Cortex | 0.3 Percentage change in BOLD signal | Standard Deviation 0.49 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Premotor Cortex | 0.1 Percentage change in BOLD signal | Standard Deviation 0.27 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Substantia Nigra/Ventral Tegemental | 0.1 Percentage change in BOLD signal | Standard Deviation 0.18 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Thalamus | 0.1 Percentage change in BOLD signal | Standard Deviation 0.24 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Visual Cortex | 0.9 Percentage change in BOLD signal | Standard Deviation 0.72 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Anterior Insula | 0.0 Percentage change in BOLD signal | Standard Deviation 0.18 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Dorsal Anterior Cingulate Cortex | 0.2 Percentage change in BOLD signal | Standard Deviation 0.34 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Dorsolateral Pre-Frontal Cortex | 0.2 Percentage change in BOLD signal | Standard Deviation 0.45 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Parietal Cortex | 0.2 Percentage change in BOLD signal | Standard Deviation 0.46 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Premotor Cortex | 0.1 Percentage change in BOLD signal | Standard Deviation 0.47 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Thalamus | -0.1 Percentage change in BOLD signal | Standard Deviation 0.22 |
| Nicotine Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Visual Cortex | 0.0 Percentage change in BOLD signal | Standard Deviation 0.44 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Anterior Insula | 0.2 Percentage change in BOLD signal | Standard Deviation 0.27 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Dorsolateral Pre-Frontal Cortex | 0.1 Percentage change in BOLD signal | Standard Deviation 0.25 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Parietal Cortex | 0.2 Percentage change in BOLD signal | Standard Deviation 0.37 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Visual Cortex | -0.1 Percentage change in BOLD signal | Standard Deviation 0.32 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Premotor Cortex | 0.1 Percentage change in BOLD signal | Standard Deviation 0.24 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Premotor Cortex | 0.2 Percentage change in BOLD signal | Standard Deviation 0.33 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Substantia Nigra/Ventral Tegemental | 0.1 Percentage change in BOLD signal | Standard Deviation 0.29 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Thalamus | 0.1 Percentage change in BOLD signal | Standard Deviation 0.36 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Visual Cortex | 0.9 Percentage change in BOLD signal | Standard Deviation 0.73 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Anterior Insula | 0.1 Percentage change in BOLD signal | Standard Deviation 0.24 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Thalamus | 0.0 Percentage change in BOLD signal | Standard Deviation 0.44 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Dorsal Anterior Cingulate Cortex | 0.2 Percentage change in BOLD signal | Standard Deviation 0.17 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Dorsolateral Pre-Frontal Cortex | 0.2 Percentage change in BOLD signal | Standard Deviation 0.37 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Anterior Putamen | 0.1 Percentage change in BOLD signal | Standard Deviation 0.36 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Parietal Cortex | 0.2 Percentage change in BOLD signal | Standard Deviation 0.52 |
| Placebo Lozenge 1 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Dorsal Anterior Cingulate Cortex | 0.4 Percentage change in BOLD signal | Standard Deviation 0.31 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Premotor Cortex | 0.7 Percentage change in BOLD signal | Standard Deviation 0.61 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Thalamus | 0.5 Percentage change in BOLD signal | Standard Deviation 0.36 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Visual Cortex | 1.6 Percentage change in BOLD signal | Standard Deviation 0.73 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Visual Cortex | 0.4 Percentage change in BOLD signal | Standard Deviation 0.43 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Anterior Insula | 0.5 Percentage change in BOLD signal | Standard Deviation 0.35 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Anterior Putamen | 0.3 Percentage change in BOLD signal | Standard Deviation 0.27 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Dorsolateral Pre-Frontal Cortex | 1.0 Percentage change in BOLD signal | Standard Deviation 0.85 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Anterior Insula | 0.7 Percentage change in BOLD signal | Standard Deviation 0.48 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Dorsolateral Pre-Frontal Cortex | 0.7 Percentage change in BOLD signal | Standard Deviation 0.77 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Dorsal Anterior Cingulate Cortex | 0.8 Percentage change in BOLD signal | Standard Deviation 0.57 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Parietal Cortex | 1.5 Percentage change in BOLD signal | Standard Deviation 0.9 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Dorsal Anterior Cingulate Cortex | 1.4 Percentage change in BOLD signal | Standard Deviation 0.7 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Parietal Cortex | 1.1 Percentage change in BOLD signal | Standard Deviation 0.62 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Premotor Cortex | 0.9 Percentage change in BOLD signal | Standard Deviation 0.69 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Thalamus | 0.7 Percentage change in BOLD signal | Standard Deviation 0.44 |
| Nicotine Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Substantia Nigra/Ventral Tegemental | 0.4 Percentage change in BOLD signal | Standard Deviation 0.28 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Dorsolateral Pre-Frontal Cortex | 0.8 Percentage change in BOLD signal | Standard Deviation 0.55 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Anterior Insula | 0.7 Percentage change in BOLD signal | Standard Deviation 0.39 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Parietal Cortex | 1.2 Percentage change in BOLD signal | Standard Deviation 0.59 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Thalamus | 0.6 Percentage change in BOLD signal | Standard Deviation 0.39 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Premotor Cortex | 0.8 Percentage change in BOLD signal | Standard Deviation 0.62 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Visual Cortex | 0.3 Percentage change in BOLD signal | Standard Deviation 0.32 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Premotor Cortex | 0.7 Percentage change in BOLD signal | Standard Deviation 0.46 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Visual Cortex | 1.9 Percentage change in BOLD signal | Standard Deviation 0.87 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Dorsolateral Pre-Frontal Cortex | 0.7 Percentage change in BOLD signal | Standard Deviation 0.59 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Dorsal Anterior Cingulate Cortex | 1.0 Percentage change in BOLD signal | Standard Deviation 0.66 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Parietal Cortex | 1.2 Percentage change in BOLD signal | Standard Deviation 0.72 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Anterior Insula | 0.5 Percentage change in BOLD signal | Standard Deviation 0.4 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Substantia Nigra/Ventral Tegemental | 0.3 Percentage change in BOLD signal | Standard Deviation 0.33 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Left Anterior Putamen | 0.3 Percentage change in BOLD signal | Standard Deviation 0.34 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Dorsal Anterior Cingulate Cortex | 0.8 Percentage change in BOLD signal | Standard Deviation 0.49 |
| Placebo Lozenge 2 | Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task | BOLD - Right Thalamus | 0.6 Percentage change in BOLD signal | Standard Deviation 0.55 |
Comparison: Region of Interest is left anterior insula.p-value: 0.296ANOVA
Comparison: Region of interest is left anterior insula.p-value: 0.345ANOVA
Comparison: Region of interest is left anterior putamen.p-value: 0.1192ANOVA
Comparison: Region of interest is left anterior putamen.p-value: 0.6639ANOVA
Comparison: Region of interest is left dorsal anterior cingulate cortex.p-value: 0.8295ANOVA
Comparison: Region of interest is left dorsal anterior cingulate cortex.p-value: 0.0078ANOVA
Comparison: Region of interest is left dorsolateral pre-frontal cortex.p-value: 0.7153ANOVA
Comparison: Region of interest is left dorsolateral pre-frontal cortexp-value: 0.8511ANOVA
Comparison: Region of interest is left parietal cortexp-value: 0.4228ANOVA
Comparison: Region of interest is left parietal cortexp-value: 0.0611ANOVA
Comparison: Region of interest is left premotor cortexp-value: 0.9879ANOVA
Comparison: Region of interest is left premotor cortexp-value: 0.2065ANOVA
Comparison: Region of interest is left substantia nigra/ventral tegmental areap-value: 0.1837ANOVA
Comparison: Region of interest is left substantia nigra/ventral tegmental areap-value: 0.8195ANOVA
Comparison: Region of interest is left thalamusp-value: 0.642ANOVA
Comparison: Region of interest is left thalamusp-value: 0.7475ANOVA
Comparison: Region of interest is left visual cortexp-value: 0.9049ANOVA
Comparison: Region of interest is left visual cortexp-value: 0.183ANOVA
Comparison: Region of interest is right anterior insulap-value: 0.5318ANOVA
Comparison: Region of interest is right anterior insulap-value: 0.9588ANOVA
Comparison: Region of interest is right dorsal anterior cingulate cortexp-value: 0.7551ANOVA
Comparison: Region of interest is right dorsal anterior cingulate cortexp-value: 0.7895ANOVA
Comparison: Region of interest is right dorsolateral pre-frontal cortexp-value: 0.9494ANOVA
Comparison: Region of interest is right dorsolateral pre-frontal cortexp-value: 0.4482ANOVA
Comparison: Region of interest is right parietal cortexp-value: 0.9343ANOVA
Comparison: Region of interest is right parietal cortexp-value: 0.7711ANOVA
Comparison: Region of interest is right premotor cortexp-value: 0.4755ANOVA
Comparison: Region of interest is right premotor cortexp-value: 0.3982ANOVA
Comparison: Region of interest is right thalamusp-value: 0.4622ANOVA
Comparison: Region of interest is right thalamusp-value: 0.4604ANOVA
Comparison: Region of interest is right visual cortexp-value: 0.2485ANOVA
Comparison: Region of interest is right visual cortexp-value: 0.1931ANOVA
Secondary
Mean Percentage of Correct Responses During DIA Task
Mean percentage of correct responses during DIA task was determined.
Time frame: Approximately 2 hours post dose administration
Population: Number of subjects with complete imaging data on both treatments (nicotine and placebo)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine Lozenge 1 | Mean Percentage of Correct Responses During DIA Task | 48.2 Percentage of responses correct | Standard Deviation 0.97 |
| Placebo Lozenge 1 | Mean Percentage of Correct Responses During DIA Task | 47.8 Percentage of responses correct | Standard Deviation 1.15 |
| Nicotine Lozenge 2 | Mean Percentage of Correct Responses During DIA Task | 96.9 Percentage of responses correct | Standard Deviation 3.48 |
| Placebo Lozenge 2 | Mean Percentage of Correct Responses During DIA Task | 95.9 Percentage of responses correct | Standard Deviation 3.61 |
Comparison: Null hypothesis considered treatments in comparison to be equal.p-value: 0.54ANOVA
Comparison: Null hypothesis considered the treatments in comparison to be equal.p-value: 0.18ANOVA
Secondary
Mean Percentage of Correct Responses During RVIP Task
Percentage of correct responses during RVIP task was determined
Time frame: Approximately 2 hours post dose administration
Population: Number of participants with complete imaging data on both treatments (nicotine and placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine Lozenge 1 | Mean Percentage of Correct Responses During RVIP Task | 92.6 Percentage of responses correct | Standard Deviation 5.27 |
| Placebo Lozenge 1 | Mean Percentage of Correct Responses During RVIP Task | 91.1 Percentage of responses correct | Standard Deviation 4.32 |
| Nicotine Lozenge 2 | Mean Percentage of Correct Responses During RVIP Task | 62.4 Percentage of responses correct | Standard Deviation 18.51 |
| Placebo Lozenge 2 | Mean Percentage of Correct Responses During RVIP Task | 54.1 Percentage of responses correct | Standard Deviation 15.38 |
Comparison: Null hypothesis considered treatments in comparison to be equal.p-value: 0.6261ANOVA
Comparison: Null hypothesis considered treatments in comparison to be equal.p-value: 0.0106ANOVA
Secondary
Mean Response Time for Correct Responses During DIA Task
DIA task comprised of three conditions: i) Sustained visual attention wherein participant responded to letter s every time it appeared in a continuous stream of letters on a screen; ii) Sustained auditory attention wherein participant responded to the number 8 each time in appeared in a continuous stream of numbers presented through headphones; iii) Divided attention task auditory and visual stimuli wherein participant responded to occurrences of s (visual) and 8 (auditory) simultaneously. Mean response time for correct responses was determined.
Time frame: Approximately 2 hours post dose administration
Population: Number of participants with complete imaging data on both treatments (nicotine and placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine Lozenge 1 | Mean Response Time for Correct Responses During DIA Task | 0.4 msec | Standard Deviation 0.04 |
| Placebo Lozenge 1 | Mean Response Time for Correct Responses During DIA Task | 0.5 msec | Standard Deviation 0.04 |
| Nicotine Lozenge 2 | Mean Response Time for Correct Responses During DIA Task | 0.5 msec | Standard Deviation 0.04 |
| Placebo Lozenge 2 | Mean Response Time for Correct Responses During DIA Task | 0.5 msec | Standard Deviation 0.04 |
Comparison: Null hypothesis considered response time of treatments in comparison to be equal.p-value: 0.1963ANOVA
Comparison: Null hypothesis considered response time of treatments in comparison to be equal.p-value: 0.0959ANOVA
Secondary
Mean Response Time for Correct Responses During RVIP Task
During the RVIP task, participants responded 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, participants responded to single occurrences of the number 0. Mean response time for correct responses was determined.
Time frame: Approximately 2 hours post dose administration
Population: Number of participants with complete imaging data on both treatments (nicotine and placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine Lozenge 1 | Mean Response Time for Correct Responses During RVIP Task | 0.5 milliseconds (msec) | Standard Deviation 0.05 |
| Placebo Lozenge 1 | Mean Response Time for Correct Responses During RVIP Task | 0.5 milliseconds (msec) | Standard Deviation 0.05 |
| Nicotine Lozenge 2 | Mean Response Time for Correct Responses During RVIP Task | 0.5 milliseconds (msec) | Standard Deviation 0.08 |
| Placebo Lozenge 2 | Mean Response Time for Correct Responses During RVIP Task | 0.5 milliseconds (msec) | Standard Deviation 0.06 |
Comparison: Null hypothesis considered the response time of treatments in comparison to be equal.p-value: 0.4535ANOVA
Comparison: Null hypothesis considered the response time of treatments in comparison to be equal.p-value: 0.1811ANOVA
Secondary
Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task
BOLD fMRI signals evaluated different brain ROIs during DIA task which comprised of three conditions: i) Sustained visual attention wherein participant responded to letter s every time it appeared in a continuous stream of letters on a screen; ii) Sustained auditory attention wherein participant responded to the number 8 each time in appeared in a continuous stream of numbers presented through headphones; iii) Divided attention task auditory and visual stimuli wherein participant responded to occurrences of s (visual) and 8 (auditory) simultaneously. Brain ROIs were right and left parietal cortex, visual cortex, superior occipital cortex and right premotor cortex.
Time frame: Approximately 2 hours post dose admininstration
Population: Number of participants with complete imaging data on both treatments (nicotine and placebo).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotine Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Parietal Cortex | -0.1 Percentage change in BOLD signal | Standard Deviation 0.55 |
| Nicotine Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Left Parietal Cortex | 0.0 Percentage change in BOLD signal | Standard Deviation 0.39 |
| Nicotine Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Left Visual Cortex | -0.1 Percentage change in BOLD signal | Standard Deviation 0.48 |
| Nicotine Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Superior Occipital Cortex | 0.0 Percentage change in BOLD signal | Standard Deviation 0.37 |
| Nicotine Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Visual Cortex | 0.0 Percentage change in BOLD signal | Standard Deviation 0.54 |
| Nicotine Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Premotor Cortex | 0.1 Percentage change in BOLD signal | Standard Deviation 0.35 |
| Nicotine Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Left Superior Occipital Cortex | -0.1 Percentage change in BOLD signal | Standard Deviation 0.32 |
| Placebo Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Left Visual Cortex | -0.1 Percentage change in BOLD signal | Standard Deviation 0.41 |
| Placebo Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Superior Occipital Cortex | 0.0 Percentage change in BOLD signal | Standard Deviation 0.46 |
| Placebo Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Visual Cortex | 0.0 Percentage change in BOLD signal | Standard Deviation 0.68 |
| Placebo Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Left Superior Occipital Cortex | 0.0 Percentage change in BOLD signal | Standard Deviation 0.28 |
| Placebo Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Parietal Cortex | -0.1 Percentage change in BOLD signal | Standard Deviation 0.63 |
| Placebo Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Left Parietal Cortex | 0.1 Percentage change in BOLD signal | Standard Deviation 0.33 |
| Placebo Lozenge 1 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Premotor Cortex | 0.2 Percentage change in BOLD signal | Standard Deviation 0.57 |
| Nicotine Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Left Parietal Cortex | 0.7 Percentage change in BOLD signal | Standard Deviation 0.44 |
| Nicotine Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Parietal Cortex | 0.5 Percentage change in BOLD signal | Standard Deviation 0.45 |
| Nicotine Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Premotor Cortex | 0.5 Percentage change in BOLD signal | Standard Deviation 0.33 |
| Nicotine Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Superior Occipital Cortex | 0.5 Percentage change in BOLD signal | Standard Deviation 0.43 |
| Nicotine Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Left Visual Cortex | 0.8 Percentage change in BOLD signal | Standard Deviation 0.42 |
| Nicotine Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Visual Cortex | 1.0 Percentage change in BOLD signal | Standard Deviation 1.13 |
| Nicotine Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Left Superior Occipital Cortex | 0.4 Percentage change in BOLD signal | Standard Deviation 0.4 |
| Placebo Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Visual Cortex | 1.2 Percentage change in BOLD signal | Standard Deviation 1.21 |
| Placebo Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Left Superior Occipital Cortex | 0.4 Percentage change in BOLD signal | Standard Deviation 0.33 |
| Placebo Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Left Visual Cortex | 0.6 Percentage change in BOLD signal | Standard Deviation 0.54 |
| Placebo Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Parietal Cortex | 0.5 Percentage change in BOLD signal | Standard Deviation 0.39 |
| Placebo Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Premotor Cortex | 0.7 Percentage change in BOLD signal | Standard Deviation 0.58 |
| Placebo Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Right Superior Occipital Cortex | 0.5 Percentage change in BOLD signal | Standard Deviation 0.53 |
| Placebo Lozenge 2 | Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task | Left Parietal Cortex | 0.6 Percentage change in BOLD signal | Standard Deviation 0.4 |
Comparison: Region of interest is left parietal cortex.p-value: 0.5544ANOVA
Comparison: Region of interest is left parietal cortex.p-value: 0.6716ANOVA
Comparison: Region of interest is left superior occipital cortex.p-value: 0.7511ANOVA
Comparison: Region of interest is left superior occipital cortex.p-value: 0.7959ANOVA
Comparison: Region of interest is left visual cortex.p-value: 0.6418ANOVA
Comparison: Region of interest is left visual cortex.p-value: 0.2205ANOVA
Comparison: Region of interest is right parietal cortex.p-value: 0.5135ANOVA
Comparison: Region of interest is right parietal cortex.p-value: 0.9781ANOVA
Comparison: Region of interest is right premotor cortex.p-value: 0.3755ANOVA
Comparison: Region of interest is right premotor cortex.p-value: 0.2612ANOVA
Comparison: Region of interest is right superior occipital cortex.p-value: 0.8486ANOVA
Comparison: Region of interest is right superior occipital cortex.p-value: 0.8318ANOVA
Comparison: Region of interest is right visual cortex.p-value: 0.7554ANOVA
Comparison: Region of interest is right visual cortex.p-value: 0.5421ANOVA