SmokingPhase 4NCT00657020

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

A Phase 4 study testing Nicotine in people with Smoking, run by GlaxoSmithKline.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Smoking
What is being tested?: Nicotine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 23 participants
Where: No sites listed yet
Study dates: Sep 2007to Feb 2008
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Weight and size
Body mass index (BMI) within the range 19.0-32.0 kg/m.
Able to fit comfortably within the MR scanner.
Smoking Status
Cigarette smokers that consume their first manufactured cigarette (i.e., not self rolled cigarettes) within 30 min of waking.
Individuals who have smoked regularly for at least a year.

Show all 10Show fewer

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.

Who cannot join

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

Show all 25Show fewer

Intracranial aneurysm clips
History of intra-orbital metal fragments that have not been removed by a doctor (as confirmed by orbital X-Ray).
Inner ear implants.
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.
History of claustrophobia or subject feels unable to lie still on their back for a period of 90 min in the MR scanner.
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
Use of any central nervous system (CNS) active, prescription medication within 14 days of first treatment visit.
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.
Current use of any nicotine replacement therapy.
Clinical Study/Experimental Medication
Participation in another clinical study or receipt of an investigational drug within 3 months of the first treatment visit.
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
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.
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).

About this study

Official title: Simultaneous fMRI/EEG of the 4 mg Nicotine Lozenge in Relief of Cognitive Impairment Associated With Nicotine Withdrawal

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

Read the 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.

Conditions: Smoking
Being tested: Nicotine, Placebo
Keywords: nicotine, therapy, fMRI/EEG, replacement
Medical subject headings: Smoking

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NicotineDrug
Nicotine lozenge containing 4 mg of nicotine
PlaceboDrug
Placebo lozenge

Study groups in NCT00657020
Study group	Role	What they receive
Nicotine lozenge	Experimental	Nicotine lozenge containing 4 mg of nicotine to be placed in mouth and suck to dissolution. Receives: Drug: Nicotine
Placebo lozenge	Placebo comparator	Placebo lozenge to be placed in mouth and suck to dissolution. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Approximately 2 hours post dose administration

Secondary outcomes (5)

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.
Measured: Approximately 2 hours post dose administration
Mean Percentage of Correct Responses During RVIP Task
Percentage of correct responses during RVIP task was determined
Measured: Approximately 2 hours post dose administration
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.
Measured: Approximately 2 hours post dose admininstration
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.
Measured: Approximately 2 hours post dose administration
Mean Percentage of Correct Responses During DIA Task
Mean percentage of correct responses during DIA task was determined.
Measured: Approximately 2 hours post dose administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2007Feb 2008

First posted14 Apr 2008 (estimated)
Study startSep 2007
Primary completionFeb 2008
Study completionFeb 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for SmokingStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00657020
Sponsor's protocol ID: S3250493
Status last verified: Jun 2013
First submitted: 2 Apr 2008
Last updated: 2 Mar 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
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Using Smartwatches to Monitor Smoking in Real-life Situations
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PROMETHEE: A Shared Interregional Tele-Tobacco Cessation Platform Embedded Within the IMPULSION Lung Cancer Screening Program
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Recruiting
Effectiveness of Volitional Help Sheets as an Adjunct to Treatment to Promote Behavior Change: A Pilot Study on Smoking
Tobacco Dependence
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Impacto 2.0: Mobile Smoking Cessation Across Texas
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All Smoking trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Simultaneous fMRI/EEG of the 4 mg Nicotine Lozenge in Relief of Cognitive Impairment Associated With Nicotine Withdrawal
ClinicalTrials.gov ID: NCT00657020
Acronym / sponsor ID: S3250493
Conditions: Smoking
Keywords: nicotine, therapy, fMRI/EEG, replacement
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 23 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: Sep 2007
Primary completion: Feb 2008 (actual)
Study completion: Feb 2008 (actual)
First posted: 14 Apr 2008 (estimated)
Results: Posted 6 Apr 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Nicotine lozenge	Experimental	Drug: NicotineNicotine lozenge containing 4 mg of nicotine to be placed in mouth and suck to dissolution.
Placebo lozenge	Placebo comparator	Drug: PlaceboPlacebo lozenge to be placed in mouth and suck to dissolution.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (10 listed)

Weight and size
Smoking Status
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.

Key exclusion criteria (25 listed)

Women who are pregnant or who have a positive urine pregnancy test or
who are breast-feeding.
Disease/Illness
Contraindications to MR scanning
Prior/Concomitant Medication

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NicotineNicotine lozenge containing 4 mg of nicotine	Drug	Nicotine lozenge
PlaceboPlacebo lozenge	Drug	Placebo lozenge

Primary outcome

Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task
Time frame: 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.

5 secondary outcomes

Mean Response Time for Correct Responses During RVIP Task
Time frame: Approximately 2 hours post dose administration
Mean Percentage of Correct Responses During RVIP Task
Time frame: Approximately 2 hours post dose administration
Percent Mean Change in BOLD Scores During Divided Attention (DIA) Task
Time frame: Approximately 2 hours post dose admininstration
Mean Response Time for Correct Responses During DIA Task
Time frame: Approximately 2 hours post dose administration
Mean Percentage of Correct Responses During DIA Task
Time frame: Approximately 2 hours post dose administration

Results and safety

Results posted to the registry on 6 Apr 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
4 mg Nicotine Lozenge Then Placebo Lozenge	11	11
Placebo Lozenge Then 4 mg Nicotine Lozenge	12	11

Primary outcome: Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task

Time frame: Approximately 2 hours post dose administration. Mean (Standard Deviation). Unit: Percentage change in BOLD signal

Measure	Nicotine Lozenge 1 n = 18	Placebo Lozenge 1 n = 18	Nicotine Lozenge 2 n = 18	Placebo Lozenge 2 n = 18
BOLD - Left Anterior Insula	0.0 (0.21)	0.2 (0.27)	0.7 (0.48)	0.7 (0.39)
BOLD - Left Anterior Putamen	0.0 (0.20)	0.1 (0.36)	0.3 (0.27)	0.3 (0.34)
BOLD - Left Dorsal Anterior Cingulate Cortex	0.3 (0.39)	0.4 (0.31)	1.4 (0.70)	1.0 (0.66)
BOLD - Left Dorsolateral Pre-Frontal Cortex	0.0 (0.29)	0.1 (0.25)	0.7 (0.77)	0.7 (0.59)
BOLD - Left Parietal Cortex	0.3 (0.49)	0.2 (0.37)	1.5 (0.90)	1.2 (0.59)
BOLD - Left Premotor Cortex	0.1 (0.27)	0.1 (0.24)	0.9 (0.69)	0.7 (0.46)
BOLD - Left Substantia Nigra/Ventral Tegemental	0.1 (0.18)	0.1 (0.29)	0.4 (0.28)	0.3 (0.33)
BOLD - Left Thalamus	0.1 (0.24)	0.1 (0.36)	0.5 (0.36)	0.6 (0.39)

Nicotine Lozenge 1 vs Placebo Lozenge 1: p = 0.2960, ANOVA
Nicotine Lozenge 2 vs Placebo Lozenge 2: p = 0.3450, ANOVA
Nicotine Lozenge 1 vs Placebo Lozenge 1: p = 0.1192, ANOVA

Population analysed: Number of participants with complete imaging data on both treatments (nicotine and placebo).

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Nicotine Lozenge	0 of 22 (0%)	4 of 22 (18.2%)	Not reported
Placebo Lozenge	0 of 23 (0%)	0 of 23 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Smoking

Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
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Enrolling by invitationObservational study
Using Smartwatches to Monitor Smoking in Real-life Situations
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PROMETHEE: A Shared Interregional Tele-Tobacco Cessation Platform Embedded Within the IMPULSION Lung Cancer Screening Program
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Nicotine in people with Smoking, run by GlaxoSmithKline.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Apr 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Rapid Visual Information Processing (RVIP) Task (time frame: Approximately 2 hours post dose administration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00657020.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2015.