HealthyPhase 1FNC-nicotineNCT02499757
Does Sweet Taste Potentiate Nicotine Cue Reactivity?
A Phase 1 study testing flavor and sweetener, flavor and nicotine and flavor, nicotine and sweetener in people with Healthy, run by Yale University at 1 site in United States.
Trial summary
The investigators' aim is to test the prediction that sweet taste perception enhances the ability of nicotine to induce neural plastic changes in brain reward circuits to increase the saliency, liking and brain reactivity to the sight and vaporized flavor of electronic cigarettes (e-cigarettes). Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- flavor and sweetener, flavor and nicotine and flavor, nicotine and sweetener
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- May 2015to Nov 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- right handed
- non-daily smoker
- english speaking
Who cannot join
- serious or unstable medical illness (e.g., cancer);
- past or current history of alcoholism or consistent drug use;
- current and history of major psychiatric illness as defined by the DSM-IV criteria including eating disorders,
- medications that affect alertness (e.g., barbiturates, benzodiazepines, chloral hydrate, haloperidol, lithium, carbamazepine, phenytoin, etc.) and any psychoactive drugs or anti-obesity agents;
- history of major head trauma with loss of consciousness;
- ongoing pregnancy;
Show all 12Show fewer
- known taste or smell dysfunction;
- a diagnosis of diabetes;
- any known allergies or sensitivity, including to food, vapors or odors;
- pregnant or nursing women,
- history of metalworking, injury with shrapnel or metal slivers, and major surgery;
- history of pacemaker or neurostimulator implantation m) asthma, chronic obstructive pulmonary disease, bronchitis or any other lung disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
The John B Pierce Laboratory
New Haven, Connecticut, 06519
About this study
The investigators' aim is to test the prediction that sweet taste perception enhances the ability of nicotine to induce neural plastic changes in brain reward circuits to increase the saliency, liking and brain reactivity to the sight and vaporized flavor of electronic cigarettes (e-cigarettes).
Read the detailed description
Alternative tobacco products are becoming increasingly available in the US market and are promoted as potentially less deleterious compared to cigarettes. These products are increasing in usage as either a substitution for cigarette smoking or in addition to smoking. One particular appeal is that they often combine nicotine with sweet taste and flavors, which are themselves reinforcing. The primary goal of this project is to determine if sweet taste can potentiate the reinforcing properties of nicotine. Similar to nicotine, cues predicting the availability of carbohydrates can stimulate intake, even in the absence of hunger. The investigators have developed a novel flavor-nutrient conditioning paradigm to study the reinforcing properties of carbohydrates. Novel flavors are paired with 0 or 113 kcal carbohydrate and increases in flavor-cue reactivity (change in liking and brain response) when later sampled in the absence of the carbohydrate provide a measure of the reinforcing potency. For smokers, the aroma of tobacco is a potent cue that can promote smoking behavior. Using a modified version of our conditioning paradigm, our specific aim is to test the prediction that sweet taste perception enhances the ability of nicotine to induce neural plastic changes in brain reward circuits to increase the saliency, liking and brain reactivity to the sight and vaporized flavor of electronic cigarettes (e-cigarettes). Participants will smoke e-cigarettes that contain nicotine and an unsweetened vaporized flavor, nicotine and a sweet vaporized flavor or only a sweet vaporized flavor (no nicotine). The investigators predict that response in the nucleus accumbens and hypothalamus to the sight and vaporized flavor of the e-cigarette that was paired with nicotine and sweet taste will be greater than the responses to the sight and vaporized flavors associated with the other e-cigarettes. The investigators further predict that liking and wanting will increase more for the sight and vaporized flavor associated with both nicotine and sweet taste. This finding would provide strong evidence that sweet taste potentiates the reinforcement potency of nicotine and could therefore promote use.
- Conditions
- Healthy
- Being tested
- flavor and sweetener, flavor and nicotine, flavor, nicotine and sweetener, flavor
- Keywords
- Perception, brain response, nicotine, taste
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
flavor and sweetenerDevice
maltol added as sweetener to e-cigarette with flavor
flavor and nicotineDevice
12 mg of nicotine added to e-cigarette with flavor
flavor, nicotine and sweetenerDevice
12 mg nicotine and maltol (sweetener) added to e-cigarette with flavor
flavorDevice
flavored e-cigarette stand alone without added nicotine and maltol (sweetener)
| Study group | Role | What they receive |
|---|---|---|
| flavor and sweetener | Experimental | E-cigarette with a novel flavor and sweetener added Receives: Device: flavor and sweetener |
| flavor and nicotine | Experimental | E-cigarette with a novel flavor and 12 mg nicotine added Receives: Device: flavor and nicotine |
| flavor, nicotine and sweetener | Experimental | E-cigarette with a novel flavor, sweetener, and 12 mg nicotine added Receives: Device: flavor, nicotine and sweetener |
| flavor | Experimental | E-cigarette with a novel flavor: without a sweetener and 12 mg nicotine added Receives: Device: flavor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline on Rating: Liking
At baseline and 2 days post exposure, subjects will rate 'liking' using the general Labeled Hedonic Scale (LHS). The LHS is a vertical line scale with quasi-logarithmic spaced, with the label 'most imaginable dislike' in the bottom to 'most imaginable like' in the top, with the label 'neutral' in the middle (recoded to range of -100 to +100).
Measured: 2 days
Secondary outcomes (1)
percent signal change of nucleus accumbens from fMRI
brain response in nucleus accumbens and hypothalamus (in percent signal
Measured: on average 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2015 (estimated)
- Study startMay 2015
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Dana M Small, Principal investigator, The John B. Pierce Laboratory
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02499757
- Sponsor's protocol ID
- 1408014434
- Other IDs
- P50DA036151
- Acronym
- FNC-nicotine
- Status last verified
- Mar 2020
- First submitted
- 24 Oct 2014
- Last updated
- 9 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Backinger CL, Fagan P, O'Connell ME, Grana R, Lawrence D, Bishop JA, Gibson JT. Use of other tobacco products among U.S. adult cigarette smokers: prevalence, trends and correlates. Addict Behav. 2008 Mar;33(3):472-89. doi: 10.1016/j.addbeh.2007.10.009. Epub 2007 Nov 4.
PubMed 18053653Drummond MB, Upson D. Electronic cigarettes. Potential harms and benefits. Ann Am Thorac Soc. 2014 Feb;11(2):236-42. doi: 10.1513/AnnalsATS.201311-391FR.
PubMed 24575993Fedoroff IC, Polivy J, Herman CP. The effect of pre-exposure to food cues on the eating behavior of restrained and unrestrained eaters. Appetite. 1997 Feb;28(1):33-47. doi: 10.1006/appe.1996.0057.
PubMed 9134093de Araujo IE, Lin T, Veldhuizen MG, Small DM. Metabolic regulation of brain response to food cues. Curr Biol. 2013 May 20;23(10):878-83. doi: 10.1016/j.cub.2013.04.001. Epub 2013 May 2.
PubMed 23643837Carpenter MJ, Saladin ME, Larowe SD, McClure EA, Simonian S, Upadhyaya HP, Gray KM. Craving, cue reactivity, and stimulus control among early-stage young smokers: effects of smoking intensity and gender. Nicotine Tob Res. 2014 Feb;16(2):208-15. doi: 10.1093/ntr/ntt147. Epub 2013 Sep 16.
PubMed 24042699
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Sweet Taste Potentiate Nicotine Cue Reactivity?
- ClinicalTrials.gov ID
- NCT02499757
- Acronym / sponsor ID
- FNC-nicotine / 1408014434
- Conditions
- Healthy
- Keywords
- Perception, brain response, nicotine, taste
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- May 2015
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 16 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators' aim is to test the prediction that sweet taste perception enhances the ability of nicotine to induce neural plastic changes in brain reward circuits to increase the saliency, liking and brain reactivity to the sight and vaporized flavor of electronic cigarettes (e-cigarettes).
Detailed description
Alternative tobacco products are becoming increasingly available in the US market and are promoted as potentially less deleterious compared to cigarettes. These products are increasing in usage as either a substitution for cigarette smoking or in addition to smoking. One particular appeal is that they often combine nicotine with sweet taste and flavors, which are themselves reinforcing. The primary goal of this project is to determine if sweet taste can potentiate the reinforcing properties of nicotine. Similar to nicotine, cues predicting the availability of carbohydrates can stimulate intake, even in the absence of hunger. The investigators have developed a novel flavor-nutrient conditioning paradigm to study the reinforcing properties of carbohydrates. Novel flavors are paired with 0 or 113 kcal carbohydrate and increases in flavor-cue reactivity (change in liking and brain response) when later sampled in the absence of the carbohydrate provide a measure of the reinforcing potency. For smokers, the aroma of tobacco is a potent cue that can promote smoking behavior. Using a modified version of our conditioning paradigm, our specific aim is to test the prediction that sweet taste perception enhances the ability of nicotine to induce neural plastic changes in brain reward circuits to increase the saliency, liking and brain reactivity to the sight and vaporized flavor of electronic cigarettes (e-cigarettes). Participants will smoke e-cigarettes that contain nicotine and an unsweetened vaporized flavor, nicotine and a sweet vaporized flavor or only a sweet vaporized flavor (no nicotine). The investigators predict that response in the nucleus accumbens and hypothalamus to the sight and vaporized flavor of the e-cigarette that was paired with nicotine and sweet taste will be greater than the responses to the sight and vaporized flavors associated with the other e-cigarettes. The investigators further predict that liking and wanting will increase more for the sight and vaporized flavor associated with both nicotine and sweet taste. This finding would provide strong evidence that sweet taste potentiates the reinforcement potency of nicotine and could therefore promote use.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| flavor and sweetener | Experimental | Device: flavor and sweetenerE-cigarette with a novel flavor and sweetener added |
| flavor and nicotine | Experimental | Device: flavor and nicotineE-cigarette with a novel flavor and 12 mg nicotine added |
| flavor, nicotine and sweetener | Experimental | Device: flavor, nicotine and sweetenerE-cigarette with a novel flavor, sweetener, and 12 mg nicotine added |
| flavor | Experimental | Device: flavorE-cigarette with a novel flavor: without a sweetener and 12 mg nicotine added |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- right handed
- non-daily smoker
- english speaking
Key exclusion criteria (12 listed)
- serious or unstable medical illness (e.g., cancer);
- past or current history of alcoholism or consistent drug use;
- current and history of major psychiatric illness as defined by the DSM-IV criteria including eating disorders,
- medications that affect alertness (e.g., barbiturates, benzodiazepines, chloral hydrate, haloperidol, lithium, carbamazepine, phenytoin, etc.) and any psychoactive drugs or anti-obesity agents;
- history of major head trauma with loss of consciousness;
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 |
|---|---|---|
| flavor and sweetenermaltol added as sweetener to e-cigarette with flavor | Device | flavor and sweetener |
| flavor and nicotine12 mg of nicotine added to e-cigarette with flavor | Device | flavor and nicotine |
| flavor, nicotine and sweetener12 mg nicotine and maltol (sweetener) added to e-cigarette with flavor | Device | flavor, nicotine and sweetener |
| flavorflavored e-cigarette stand alone without added nicotine and maltol (sweetener) | Device | flavor |
Primary outcome
Change from Baseline on Rating: Liking
Time frame: 2 days
At baseline and 2 days post exposure, subjects will rate 'liking' using the general Labeled Hedonic Scale (LHS). The LHS is a vertical line scale with quasi-logarithmic spaced, with the label 'most imaginable dislike' in the bottom to 'most imaginable like' in the top, with the label 'neutral' in the middle (recoded to range of -100 to +100).
1 secondary outcome
percent signal change of nucleus accumbens from fMRI
Time frame: on average 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2020.
- Background: PubMed 18053653Backinger CL, Fagan P, O'Connell ME, Grana R, Lawrence D, Bishop JA, Gibson JT. Use of other tobacco products among U.S. adult cigarette smokers: prevalence, trends and correlates. Addict Behav. 2008 Mar;33(3):472-89. doi: 10.1016/j.addbeh.2007.10.009. Epub 2007 Nov 4.
- Background: PubMed 24575993Drummond MB, Upson D. Electronic cigarettes. Potential harms and benefits. Ann Am Thorac Soc. 2014 Feb;11(2):236-42. doi: 10.1513/AnnalsATS.201311-391FR.
- Background: PubMed 9134093Fedoroff IC, Polivy J, Herman CP. The effect of pre-exposure to food cues on the eating behavior of restrained and unrestrained eaters. Appetite. 1997 Feb;28(1):33-47. doi: 10.1006/appe.1996.0057.
- Background: PubMed 23643837de Araujo IE, Lin T, Veldhuizen MG, Small DM. Metabolic regulation of brain response to food cues. Curr Biol. 2013 May 20;23(10):878-83. doi: 10.1016/j.cub.2013.04.001. Epub 2013 May 2.
- Background: PubMed 24042699Carpenter MJ, Saladin ME, Larowe SD, McClure EA, Simonian S, Upadhyaya HP, Gray KM. Craving, cue reactivity, and stimulus control among early-stage young smokers: effects of smoking intensity and gender. Nicotine Tob Res. 2014 Feb;16(2):208-15. doi: 10.1093/ntr/ntt147. Epub 2013 Sep 16.
Related trials for Healthy
RecruitingObservational study
Studies of Blood Flow to the Brain During Thought
Healthy Volunteer
Enrolling by invitationObservational study
Screening for Hematology Branch Protocols
Hematologic Disease and Disorders, Donors
Enrolling by invitationObservational study
Collection of Tissue Specimens From Patients With Solid Tumors or Blood Disorders and Their HLA-Compatible Family Members
Neoplasms, Hematologic Neoplasms
Enrolling by invitationObservational study
Collection and Distribution of Samples From Healthy Donors for In Vitro Research at the NCI-Frederick
Healthy Donors
RecruitingObservational study
Collection and Analysis of Blood, Bone Marrow, and Buccal Mucosa Samples From Healthy Volunteers
Healthy Volunteers
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.
Dana M Small principal investigator
The John B. Pierce Laboratory
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing flavor and sweetener, flavor and nicotine and flavor, nicotine and sweetener in people with Healthy, run by Yale University at 1 site in United States.
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 3 inclusion and 12 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 9 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change from Baseline on Rating: Liking (time frame: 2 days). 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 NCT02499757, which also lists 5 linked publications.
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 9 Mar 2020; AzTrials last refreshed its copy on 6 Nov 2026.