Smoking ( Cigarette)Phase 1NCT07771725
Impact of Sweeteners on the Addictive Threshold of Nicotine
A Phase 1 study testing Nicotine 0.05 mg/pulse and 0.1 mg/pulse and sucralose in people with Smoking ( Cigarette), run by Yale University at 1 site in United States.
Trial summary
To determine if sucralose, an artificial sweetener, modulates nicotine threshold doses for discrimination, subjective-rewarding effects, and reinforcement in smokers with varying levels of dependence. Read more about this study
- Who is it for?
- Ages 21 to 59 years
- Conditions the study is for
- Smoking ( Cigarette)
- What is being tested?
- Nicotine 0.05 mg/pulse and 0.1 mg/pulse and sucralose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2026to 31 Dec 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 21 to 59 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Smoking at least for one year and more frequently than once a week, smoking status confirmed with a semi-quantitative urine nicotine test. Smokers will be stratified by level of dependence, assessed with the FTND 29 low or no dependence ≤3 and moderate or high dependence ≥ 4.
- In good health as verified by medical history, screening examination, and screening laboratory tests.
- For women, report using acceptable birth control methods.
Who cannot join
- History of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the participant to be in the study;
- regular current use of certain psychotropic medications (such as mood stabilizers, antipsychotics, or anxiolytics being prescribed to treat bipolar disorder, psychosis or anxiety spectrum disorders, respectively);
- current untreated alcohol or substance use disorder for any other recreational or prescription drugs other than nicotine;
- for women, pregnant as determined by pregnancy screening, or breastfeeding; and 5) seeking (or undergoing) treatment for tobacco dependence or smoking.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Stacy A Minnix, B.S. contact
About this study
To determine if sucralose, an artificial sweetener, modulates nicotine threshold doses for discrimination, subjective-rewarding effects, and reinforcement in smokers with varying levels of dependence.
Read the detailed description
Participants will complete an Adaptation Session followed by four Test Days. The Adaptation Session will familiarize participants with all study procedures. On each Test Day, a specific intravenous nicotine dose (0.05 or 0.1 mg/pulse) is paired with either a sucralose or control flavor administered by an electronic cigarette. The experimental procedure begins with a sampling phase comparing the assigned nicotine dose against saline, each paired with the assigned flavor, followed by four trials to assess the participant's ability to discriminate between the two conditions. Subsequently, participants complete four Choice trials, where they will choose between receiving the assigned nicotine dose and saline. Reinforcement will be measured by the percentage of nicotine choices, while discrimination will be measured by the percentage of correctly identified infusions. Subjective rewarding effects will be assessed using the "Pleasurable Effects" composite score of the Drug Effects Questionnaire (DEQ).
- Conditions
- Smoking ( Cigarette)
- Being tested
- Nicotine 0.05 mg/pulse and 0.1 mg/pulse, Saline Placebo (0.5mL injection), sucralose, Sugar syrup (Placebo)
- Medical subject headings
- Cigarette Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotine 0.05 mg/pulse and 0.1 mg/pulseDrug
Nicotine will be used and compared to saline given by IV push by study physician
Saline Placebo (0.5mL injection)Drug
Saline will be used compared to the low dose of Nicotine given by IV push by study physician
sucraloseDietary supplement
sweet flavor (sucralose) compared to unsweetened flavor
Sugar syrup (Placebo)Dietary supplement
Unsweetened flavor compared to the sweetened flavor sucralose.
| Study group | Role | What they receive |
|---|---|---|
| Nicotine | Active comparator | These test days will evaluate two nicotine doses (0.05 mg/pulse and 0.1 mg/pulse) Receives: Drug: Nicotine 0.05 mg/pulse and 0.1 mg/pulse |
| saline | Placebo comparator | Saline (sugar water) Receives: Drug: Saline Placebo (0.5mL injection) |
| sucralose | Active comparator | participants practice using the e-cigarette and sample the sweet (sucralose) and control (unsweetened) flavors Receives: Dietary Supplement: sucralose |
| unsweetened flavor | Placebo comparator | participants practice using the e-cigarette and sample the sweet (sucralose) and control (unsweetened) flavors Receives: Dietary Supplement: Sugar syrup (Placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drug Discrimination Scale (DDS) score.
This scale asks the participants to select if they received Drug A or B and how confident they are in their selection on a scale of 0 to 10. Higher scores indicate more confidence.
Measured: OnTest Days 1, 2, 3 and 4
Drug Effects Questionnaire (DEQ) pleasurable effects score
The DEQ pleasurable effects consists of 11 questions with total score range from 0-100. Higher scores indicate more positive effects.
Measured: OnTest Days 1, 2, 3 and 4
Secondary outcomes (1)
Minnesota Nicotine Withdrawal Scale score
This 8-item scale will be used to assess DSM-IV symptoms of nicotine withdrawal. Total score range 0-32. Higher scores indicate more severe withdrawal symptoms.
Measured: OnTest Days 1, 2, 3 and 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2026
- Study start1 Sep 2026 (estimated)
- Primary completion1 Sep 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Smoking ( Cigarette)Studies 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
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Mehmet Sofuoglu, M.D., Ph.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07771725
- Sponsor's protocol ID
- 2000043445
- Other IDs
- 2U54DA036151-11
- Status last verified
- Aug 2026
- First submitted
- 13 Aug 2026
- Last updated
- 31 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Sweeteners on the Addictive Threshold of Nicotine
- ClinicalTrials.gov ID
- NCT07771725
- Acronym / sponsor ID
- 2000043445
- Conditions
- Smoking ( Cigarette)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 1 Sep 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 18 Aug 2026 (actual)
- 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.
To determine if sucralose, an artificial sweetener, modulates nicotine threshold doses for discrimination, subjective-rewarding effects, and reinforcement in smokers with varying levels of dependence.
Detailed description
Participants will complete an Adaptation Session followed by four Test Days. The Adaptation Session will familiarize participants with all study procedures. On each Test Day, a specific intravenous nicotine dose (0.05 or 0.1 mg/pulse) is paired with either a sucralose or control flavor administered by an electronic cigarette. The experimental procedure begins with a sampling phase comparing the assigned nicotine dose against saline, each paired with the assigned flavor, followed by four trials to assess the participant's ability to discriminate between the two conditions. Subsequently, participants complete four Choice trials, where they will choose between receiving the assigned nicotine dose and saline. Reinforcement will be measured by the percentage of nicotine choices, while discrimination will be measured by the percentage of correctly identified infusions. Subjective rewarding effects will be assessed using the "Pleasurable Effects" composite score of the Drug Effects Questionnaire (DEQ).
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Nicotine | Active comparator | Drug: Nicotine 0.05 mg/pulse and 0.1 mg/pulseThese test days will evaluate two nicotine doses (0.05 mg/pulse and 0.1 mg/pulse) |
| saline | Placebo comparator | Drug: Saline Placebo (0.5mL injection)Saline (sugar water) |
| sucralose | Active comparator | Dietary Supplement: sucraloseparticipants practice using the e-cigarette and sample the sweet (sucralose) and control (unsweetened) flavors |
| unsweetened flavor | Placebo comparator | Dietary Supplement: Sugar syrup (Placebo)participants practice using the e-cigarette and sample the sweet (sucralose) and control (unsweetened) flavors |
Who may qualify
- Ages
- 21 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Smoking at least for one year and more frequently than once a week, smoking status confirmed with a semi-quantitative urine nicotine test. Smokers will be stratified by level of dependence, assessed with the FTND 29 low or no dependence ≤3 and moderate or high dependence ≥ 4.
- In good health as verified by medical history, screening examination, and screening laboratory tests.
- For women, report using acceptable birth control methods.
Key exclusion criteria (4 listed)
- History of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the participant to be in the study;
- regular current use of certain psychotropic medications (such as mood stabilizers, antipsychotics, or anxiolytics being prescribed to treat bipolar disorder, psychosis or anxiety spectrum disorders, respectively);
- current untreated alcohol or substance use disorder for any other recreational or prescription drugs other than nicotine;
- for women, pregnant as determined by pregnancy screening, or breastfeeding; and 5) seeking (or undergoing) treatment for tobacco dependence or smoking.
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 |
|---|---|---|
| Nicotine 0.05 mg/pulse and 0.1 mg/pulseNicotine will be used and compared to saline given by IV push by study physician | Drug | Nicotine |
| Saline Placebo (0.5mL injection)Saline will be used compared to the low dose of Nicotine given by IV push by study physician | Drug | saline |
| sucralosesweet flavor (sucralose) compared to unsweetened flavor | Dietary supplement | sucralose |
| Sugar syrup (Placebo)Unsweetened flavor compared to the sweetened flavor sucralose. | Dietary supplement | unsweetened flavor |
Primary outcome
Drug Discrimination Scale (DDS) score.
Time frame: OnTest Days 1, 2, 3 and 4
This scale asks the participants to select if they received Drug A or B and how confident they are in their selection on a scale of 0 to 10. Higher scores indicate more confidence.
Drug Effects Questionnaire (DEQ) pleasurable effects score
Time frame: OnTest Days 1, 2, 3 and 4
The DEQ pleasurable effects consists of 11 questions with total score range from 0-100. Higher scores indicate more positive effects.
1 secondary outcome
Minnesota Nicotine Withdrawal Scale score
Time frame: OnTest Days 1, 2, 3 and 4
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- Individual participant dataSharing planned: No
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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.
Stacy A Minnix, B.S. contact
Mehmet Sofuoglu, M.D., Ph.D. principal investigator
Yale University
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 Nicotine 0.05 mg/pulse and 0.1 mg/pulse and sucralose in people with Smoking ( Cigarette), 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 4 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: opening soon, as of the sponsor's last update on 31 Aug 2026. 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. 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 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mehmet Sofuoglu, M.D., Ph.D. (203-932-5711, Mehmet.Sofuoglu@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Drug Discrimination Scale (DDS) score. (time frame: OnTest Days 1, 2, 3 and 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Aug 2026.