Trial Outcomes & Findings for Functional Magnetic Resonance Imaging (fMRI) Investigation of Nicotine Withdrawal Symptoms (NCT NCT00657020)
NCT ID: NCT00657020
Last Updated: 2015-03-02
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
23 participants
Primary outcome timeframe
Approximately 2 hours post dose administration
Results posted on
2015-03-02
Participant Flow
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.
Participant milestones
| Measure |
4 mg Nicotine Lozenge Then Placebo Lozenge
Participants received nicotine lozenge containing 4 milligrams (mg) of nicotine in Period I and placebo lozenge in Period II.
|
Placebo Lozenge Then 4 mg Nicotine Lozenge
Participants received placebo lozenge in Period I and nicotine 4 mg lozenge in Period II.
|
|---|---|---|
|
PERIOD 1
STARTED
|
11
|
12
|
|
PERIOD 1
COMPLETED
|
11
|
11
|
|
PERIOD 1
NOT COMPLETED
|
0
|
1
|
|
PERIOD 2
STARTED
|
11
|
11
|
|
PERIOD 2
COMPLETED
|
11
|
11
|
|
PERIOD 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
4 mg Nicotine Lozenge Then Placebo Lozenge
Participants received nicotine lozenge containing 4 milligrams (mg) of nicotine in Period I and placebo lozenge in Period II.
|
Placebo Lozenge Then 4 mg Nicotine Lozenge
Participants received placebo lozenge in Period I and nicotine 4 mg lozenge in Period II.
|
|---|---|---|
|
PERIOD 1
Adverse Event
|
0
|
1
|
Baseline Characteristics
Functional Magnetic Resonance Imaging (fMRI) Investigation of Nicotine Withdrawal Symptoms
Baseline characteristics by cohort
| Measure |
All Randomized Participants
n=23 Participants
All randomized participants who receive study treatments.
|
|---|---|
|
Age, Continuous
|
30.82 years
STANDARD_DEVIATION 8.428 • n=99 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
23 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Approximately 2 hours post dose administrationPopulation: Number of participants with complete imaging data on both treatments (nicotine and placebo).
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.
Outcome measures
| Measure |
Nicotine Lozenge 1
n=18 Participants
Participants in low attention condition and received 4 mg of nicotine lozenge.
|
Placebo Lozenge 1
n=18 Participants
Participants in low attention condition and received placebo lozenge.
|
Nicotine Lozenge 2
n=18 Participants
Participants in high attention condition and received 4 mg of nicotine lozenge.
|
Placebo Lozenge 2
n=18 Participants
Participants in high attention condition and received placebo lozenge.
|
|---|---|---|---|---|
|
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
|
0.1 Percentage change in BOLD signal
Standard Deviation 0.29
|
0.4 Percentage change in BOLD signal
Standard Deviation 0.28
|
0.3 Percentage change in BOLD signal
Standard Deviation 0.33
|
|
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
|
0.2 Percentage change in BOLD signal
Standard Deviation 0.27
|
0.7 Percentage change in BOLD signal
Standard Deviation 0.48
|
0.7 Percentage change in BOLD signal
Standard Deviation 0.39
|
|
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
|
0.4 Percentage change in BOLD signal
Standard Deviation 0.31
|
1.4 Percentage change in BOLD signal
Standard Deviation 0.70
|
1.0 Percentage change in BOLD signal
Standard Deviation 0.66
|
|
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
|
0.1 Percentage change in BOLD signal
Standard Deviation 0.24
|
0.9 Percentage change in BOLD signal
Standard Deviation 0.69
|
0.7 Percentage change in BOLD signal
Standard Deviation 0.46
|
|
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
|
0.9 Percentage change in BOLD signal
Standard Deviation 0.73
|
1.6 Percentage change in BOLD signal
Standard Deviation 0.73
|
1.9 Percentage change in BOLD signal
Standard Deviation 0.87
|
|
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
|
0.1 Percentage change in BOLD signal
Standard Deviation 0.24
|
0.5 Percentage change in BOLD signal
Standard Deviation 0.35
|
0.5 Percentage change in BOLD signal
Standard Deviation 0.40
|
|
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
|
0.2 Percentage change in BOLD signal
Standard Deviation 0.17
|
0.8 Percentage change in BOLD signal
Standard Deviation 0.57
|
0.8 Percentage change in BOLD signal
Standard Deviation 0.49
|
|
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
|
0.2 Percentage change in BOLD signal
Standard Deviation 0.52
|
1.1 Percentage change in BOLD signal
Standard Deviation 0.62
|
1.2 Percentage change in BOLD signal
Standard Deviation 0.72
|
|
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
|
0.2 Percentage change in BOLD signal
Standard Deviation 0.33
|
0.7 Percentage change in BOLD signal
Standard Deviation 0.61
|
0.8 Percentage change in BOLD signal
Standard Deviation 0.62
|
|
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
|
0.0 Percentage change in BOLD signal
Standard Deviation 0.44
|
0.7 Percentage change in BOLD signal
Standard Deviation 0.44
|
0.6 Percentage change in BOLD signal
Standard Deviation 0.55
|
|
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
|
-0.1 Percentage change in BOLD signal
Standard Deviation 0.32
|
0.4 Percentage change in BOLD signal
Standard Deviation 0.43
|
0.3 Percentage change in BOLD signal
Standard Deviation 0.32
|
|
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 0.20
|
0.1 Percentage change in BOLD signal
Standard Deviation 0.36
|
0.3 Percentage change in BOLD signal
Standard Deviation 0.27
|
0.3 Percentage change in BOLD signal
Standard Deviation 0.34
|
|
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
|
0.1 Percentage change in BOLD signal
Standard Deviation 0.25
|
0.7 Percentage change in BOLD signal
Standard Deviation 0.77
|
0.7 Percentage change in BOLD signal
Standard Deviation 0.59
|
|
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
|
0.2 Percentage change in BOLD signal
Standard Deviation 0.37
|
1.5 Percentage change in BOLD signal
Standard Deviation 0.90
|
1.2 Percentage change in BOLD signal
Standard Deviation 0.59
|
|
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
|
0.1 Percentage change in BOLD signal
Standard Deviation 0.36
|
0.5 Percentage change in BOLD signal
Standard Deviation 0.36
|
0.6 Percentage change in BOLD signal
Standard Deviation 0.39
|
|
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
|
0.2 Percentage change in BOLD signal
Standard Deviation 0.37
|
1.0 Percentage change in BOLD signal
Standard Deviation 0.85
|
0.8 Percentage change in BOLD signal
Standard Deviation 0.55
|
SECONDARY outcome
Timeframe: Approximately 2 hours post dose administrationPopulation: Number of participants with complete imaging data on both treatments (nicotine and placebo).
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.
Outcome measures
| Measure |
Nicotine Lozenge 1
n=22 Participants
Participants in low attention condition and received 4 mg of nicotine lozenge.
|
Placebo Lozenge 1
n=22 Participants
Participants in low attention condition and received placebo lozenge.
|
Nicotine Lozenge 2
n=22 Participants
Participants in high attention condition and received 4 mg of nicotine lozenge.
|
Placebo Lozenge 2
n=22 Participants
Participants in high attention condition and received placebo lozenge.
|
|---|---|---|---|---|
|
Mean Response Time for Correct Responses During RVIP Task
|
0.5 milliseconds (msec)
Standard Deviation 0.05
|
0.5 milliseconds (msec)
Standard Deviation 0.05
|
0.5 milliseconds (msec)
Standard Deviation 0.08
|
0.5 milliseconds (msec)
Standard Deviation 0.06
|
SECONDARY outcome
Timeframe: Approximately 2 hours post dose administrationPopulation: Number of participants with complete imaging data on both treatments (nicotine and placebo).
Percentage of correct responses during RVIP task was determined
Outcome measures
| Measure |
Nicotine Lozenge 1
n=22 Participants
Participants in low attention condition and received 4 mg of nicotine lozenge.
|
Placebo Lozenge 1
n=22 Participants
Participants in low attention condition and received placebo lozenge.
|
Nicotine Lozenge 2
n=22 Participants
Participants in high attention condition and received 4 mg of nicotine lozenge.
|
Placebo Lozenge 2
n=22 Participants
Participants in high attention condition and received placebo lozenge.
|
|---|---|---|---|---|
|
Mean Percentage of Correct Responses During RVIP Task
|
92.6 Percentage of responses correct
Standard Deviation 5.27
|
91.1 Percentage of responses correct
Standard Deviation 4.32
|
62.4 Percentage of responses correct
Standard Deviation 18.51
|
54.1 Percentage of responses correct
Standard Deviation 15.38
|
SECONDARY outcome
Timeframe: Approximately 2 hours post dose admininstrationPopulation: Number of participants with complete imaging data on both treatments (nicotine and placebo).
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.
Outcome measures
| Measure |
Nicotine Lozenge 1
n=19 Participants
Participants in low attention condition and received 4 mg of nicotine lozenge.
|
Placebo Lozenge 1
n=19 Participants
Participants in low attention condition and received placebo lozenge.
|
Nicotine Lozenge 2
n=19 Participants
Participants in high attention condition and received 4 mg of nicotine lozenge.
|
Placebo Lozenge 2
n=19 Participants
Participants in high attention condition and received placebo lozenge.
|
|---|---|---|---|---|
|
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
|
-0.1 Percentage change in BOLD signal
Standard Deviation 0.41
|
0.8 Percentage change in BOLD signal
Standard Deviation 0.42
|
0.6 Percentage change in BOLD signal
Standard Deviation 0.54
|
|
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
|
0.0 Percentage change in BOLD signal
Standard Deviation 0.68
|
1.0 Percentage change in BOLD signal
Standard Deviation 1.13
|
1.2 Percentage change in BOLD signal
Standard Deviation 1.21
|
|
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
|
0.1 Percentage change in BOLD signal
Standard Deviation 0.33
|
0.7 Percentage change in BOLD signal
Standard Deviation 0.44
|
0.6 Percentage change in BOLD signal
Standard Deviation 0.40
|
|
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
|
0.0 Percentage change in BOLD signal
Standard Deviation 0.28
|
0.4 Percentage change in BOLD signal
Standard Deviation 0.40
|
0.4 Percentage change in BOLD signal
Standard Deviation 0.33
|
|
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
|
-0.1 Percentage change in BOLD signal
Standard Deviation 0.63
|
0.5 Percentage change in BOLD signal
Standard Deviation 0.45
|
0.5 Percentage change in BOLD signal
Standard Deviation 0.39
|
|
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
|
0.2 Percentage change in BOLD signal
Standard Deviation 0.57
|
0.5 Percentage change in BOLD signal
Standard Deviation 0.33
|
0.7 Percentage change in BOLD signal
Standard Deviation 0.58
|
|
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
|
0.0 Percentage change in BOLD signal
Standard Deviation 0.46
|
0.5 Percentage change in BOLD signal
Standard Deviation 0.43
|
0.5 Percentage change in BOLD signal
Standard Deviation 0.53
|
SECONDARY outcome
Timeframe: Approximately 2 hours post dose administrationPopulation: Number of participants with complete imaging data on both treatments (nicotine and placebo).
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.
Outcome measures
| Measure |
Nicotine Lozenge 1
n=22 Participants
Participants in low attention condition and received 4 mg of nicotine lozenge.
|
Placebo Lozenge 1
n=22 Participants
Participants in low attention condition and received placebo lozenge.
|
Nicotine Lozenge 2
n=22 Participants
Participants in high attention condition and received 4 mg of nicotine lozenge.
|
Placebo Lozenge 2
n=22 Participants
Participants in high attention condition and received placebo lozenge.
|
|---|---|---|---|---|
|
Mean Response Time for Correct Responses During DIA Task
|
0.4 msec
Standard Deviation 0.04
|
0.5 msec
Standard Deviation 0.04
|
0.5 msec
Standard Deviation 0.04
|
0.5 msec
Standard Deviation 0.04
|
SECONDARY outcome
Timeframe: Approximately 2 hours post dose administrationPopulation: Number of subjects with complete imaging data on both treatments (nicotine and placebo)
Mean percentage of correct responses during DIA task was determined.
Outcome measures
| Measure |
Nicotine Lozenge 1
n=18 Participants
Participants in low attention condition and received 4 mg of nicotine lozenge.
|
Placebo Lozenge 1
n=18 Participants
Participants in low attention condition and received placebo lozenge.
|
Nicotine Lozenge 2
n=18 Participants
Participants in high attention condition and received 4 mg of nicotine lozenge.
|
Placebo Lozenge 2
n=18 Participants
Participants in high attention condition and received placebo lozenge.
|
|---|---|---|---|---|
|
Mean Percentage of Correct Responses During DIA Task
|
48.2 Percentage of responses correct
Standard Deviation 0.97
|
47.8 Percentage of responses correct
Standard Deviation 1.15
|
96.9 Percentage of responses correct
Standard Deviation 3.48
|
95.9 Percentage of responses correct
Standard Deviation 3.61
|
Adverse Events
Nicotine Lozenge
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo Lozenge
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Nicotine Lozenge
n=22 participants at risk
Participants in safety population received 4 mg of nicotine lozenge.
|
Placebo Lozenge
n=23 participants at risk
Participants in safety population received placebo lozenge.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
9.1%
2/22 • Number of events 4 • All adverse events encountered or spontaneously reported following administration of any investigational product (including washout product), or for up to 5 days after the last administration of investigational product were recorded.
|
0.00%
0/23 • All adverse events encountered or spontaneously reported following administration of any investigational product (including washout product), or for up to 5 days after the last administration of investigational product were recorded.
|
|
Gastrointestinal disorders
Nausea
|
9.1%
2/22 • Number of events 3 • All adverse events encountered or spontaneously reported following administration of any investigational product (including washout product), or for up to 5 days after the last administration of investigational product were recorded.
|
0.00%
0/23 • All adverse events encountered or spontaneously reported following administration of any investigational product (including washout product), or for up to 5 days after the last administration of investigational product were recorded.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place