Smoking AddictionEarly Phase 1NCT06096714
Addictive Threshold of Nicotine
A Early Phase 1 study testing Nicotine and Saline in people with Smoking Addiction, run by Yale University at 1 site in United States.
Trial summary
To determine the nicotine threshold dose(s) for discrimination, subjective-rewarding effects, -and reinforcement in smokers with different levels of dependence. Read more about this study
- Who is it for?
- Ages 21 to 59 years
- Conditions the study is for
- Smoking Addiction
- What is being tested?
- Nicotine and Saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Feb 2024to 1 Oct 2027
- Phase
- Early 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
- to contact their primary care provider when necessary.
- Adults, aged 21 to 59 years. Individuals less than 21 will be excluded because the minimum age for purchasing tobacco products is 21 in our state. The upper age is set at 59 because there are no previous IV nicotine studies that enrolled smokers over the age of 59.
- 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 based on the level of dependence, assessed with the FTND scores (Heatherton et al. 1991) (low or no dependence 4 and moderate or high level of dependence 5.
- 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
- 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.
United States1 site, 1 recruiting
- Recruiting
VA Healthcare System
West Haven, Connecticut, 06516
Mehmet Sofuoglu, M.D.,Ph.D.
About this study
To determine the nicotine threshold dose(s) for discrimination, subjective-rewarding effects, -and reinforcement in smokers with different levels of dependence.
Read the detailed description
The purpose of this project is to determine the nicotine threshold dose(s) for discrimination, subjective-rewarding effects, and reinforcement in smokers with different levels of dependence. Participants will have an Adaptation Session followed by 4 Test Days. The Adaptation Session will familiarize the participants with study procedures. In each Test Day, a different nicotine dose (0.1, 0.05, 0.025, and 0.0125 mg nicotine/pulse) will be compared to saline for nicotine discrimination, subjective effects, and reinforcement. Participants will first sample the assigned nicotine dose and saline, followed by 4 trials to test their ability to discriminate it from saline. This will be followed by 4 Choice trials where participants will be able to choose between nicotine (at the session-assigned dose) or saline to be administered by the research staff.
Reinforcement will be assessed with the percentage of nicotine choices during the Choice trials. The discrimination is the percentage of correctly identified nicotine and saline infusions. Rewarding effects will be assessed with the "Pleasurable Effects" composite score of the Drug Effects Questionnaire (DEQ).
- Conditions
- Smoking Addiction
- Being tested
- Nicotine, Saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NicotineDrug
Nicotine will be infused using a pump.
SalineOther
Saline with be used to compare Nicotine, Saline will be infused using a pump
| Study group | Role | What they receive |
|---|---|---|
| Nicotine | Active comparator | Adaptation Session followed by 4 Test Days. The Adaptation Session will familiarize the participants with study procedures. In each Test Day, a different nicotine dose (0.1, 0.05, 0.025, and 0.0125 mg nicotine/pulse) will be compared to saline for nicotine discrimination, subjective effects, and reinforcement. Participants will first sample the assigned nicotine dose and saline, followed by 4 trials to test their ability to discriminate it from saline. This will be followed by 4 Choice trials where participants will be able to choose between nicotine (at the session-assigned dose) or saline (A or B). Receives: Drug: Nicotine; Other: Saline |
| saline | Placebo comparator | Subjects will have sample A and B, one being nicotine and one being saline. The doses will be blinded from PI, subject and staff. The subject must choose A or B for the next ten choices. Receives: Drug: Nicotine; Other: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
correctly identifying nicotine
Reinforcement will be assessed with the percentage of nicotine doses chosen during the Choice trials (out of 16), 4 choices per day over four days.
Measured: up to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2023
- Study start27 Feb 2024
- Primary completion1 Sep 2027 (estimated)
- Study completion1 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Smoking AddictionStudies 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
- Early Phase 1
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 45 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06096714
- Sponsor's protocol ID
- 2000036324
- Other IDs
- 2U54DA036151-11
- Status last verified
- Jun 2026
- First submitted
- 12 Oct 2023
- Last updated
- 11 Jun 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 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Addictive Threshold of Nicotine
- ClinicalTrials.gov ID
- NCT06096714
- Acronym / sponsor ID
- 2000036324
- Conditions
- Smoking Addiction
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 27 Feb 2024 (actual)
- Primary completion
- 1 Sep 2027 (estimated)
- Study completion
- 1 Oct 2027 (estimated)
- First posted
- 24 Oct 2023 (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 the nicotine threshold dose(s) for discrimination, subjective-rewarding effects, -and reinforcement in smokers with different levels of dependence.
Detailed description
The purpose of this project is to determine the nicotine threshold dose(s) for discrimination, subjective-rewarding effects, and reinforcement in smokers with different levels of dependence. Participants will have an Adaptation Session followed by 4 Test Days. The Adaptation Session will familiarize the participants with study procedures. In each Test Day, a different nicotine dose (0.1, 0.05, 0.025, and 0.0125 mg nicotine/pulse) will be compared to saline for nicotine discrimination, subjective effects, and reinforcement. Participants will first sample the assigned nicotine dose and saline, followed by 4 trials to test their ability to discriminate it from saline. This will be followed by 4 Choice trials where participants will be able to choose between nicotine (at the session-assigned dose) or saline to be administered by the research staff.
Reinforcement will be assessed with the percentage of nicotine choices during the Choice trials. The discrimination is the percentage of correctly identified nicotine and saline infusions. Rewarding effects will be assessed with 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
- 2
| Arm | Type | Receives |
|---|---|---|
| Nicotine | Active comparator | Drug: Nicotine, Other: SalineAdaptation Session followed by 4 Test Days. The Adaptation Session will familiarize the participants with study procedures. In each Test Day, a different nicotine dose (0.1, 0.05, 0.025, and 0.0125 mg nicotine/pulse) will be compared to saline for nicotine discrimination, subjective effects, and reinforcement. Participants will first sample the assigned nicotine dose and saline, followed by 4 trials to test their ability to discriminate it from saline. This will be followed by 4 Choice trials where participants will be able to choose between nicotine (at the session-assigned dose) or saline (A or B). |
| saline | Placebo comparator | Drug: Nicotine, Other: SalineSubjects will have sample A and B, one being nicotine and one being saline. The doses will be blinded from PI, subject and staff. The subject must choose A or B for the next ten choices. |
Who may qualify
- Ages
- 21 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- to contact their primary care provider when necessary.
- Adults, aged 21 to 59 years. Individuals less than 21 will be excluded because the minimum age for purchasing tobacco products is 21 in our state. The upper age is set at 59 because there are no previous IV nicotine studies that enrolled smokers over the age of 59.
- 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 based on the level of dependence, assessed with the FTND scores (Heatherton et al. 1991) (low or no dependence 4 and moderate or high level of dependence 5.
- 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 (5 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
- 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 |
|---|---|---|
| NicotineNicotine will be infused using a pump. | Drug | Nicotine, saline |
| SalineSaline with be used to compare Nicotine, Saline will be infused using a pump | Other | Nicotine, saline |
Primary outcome
correctly identifying nicotine
Time frame: up to 8 weeks
Reinforcement will be assessed with the percentage of nicotine doses chosen during the Choice trials (out of 16), 4 choices per day over four days.
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 11 Jun 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Nicotine and Saline in people with Smoking Addiction, 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 5 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 11 Jun 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 Stacy Minnix, B.S (203-932-5711, stacy.minnix@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
correctly identifying nicotine (time frame: up to 8 weeks). 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 11 Jun 2026.