Nicotine DependenceEarly Phase 1NCT05176418
IV Pulsed-Nicotine as a Model of Smoking: The Effects of Dose and Delivery Rate
A Early Phase 1 study testing low dose Nicotine and high dose Nicotine in people with Nicotine Dependence, run by Yale University at 1 site in United States.
Trial summary
This project will examine the impact of the nicotine dose and delivery rate on nicotine's abuse potential, versus its potentially beneficial effects on smoking urges and withdrawal. Will use pulsed IV nicotine administration which closely matches nicotine delivery by inhaled tobacco use. Read more about this study
- Who is it for?
- Ages 21 to 55 years
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- low dose Nicotine and high dose Nicotine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Sep 2022to 8 Oct 2025
- Phase
- Early 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 21 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Female and male, aged 21 to 55 years;
- past year daily cigarette use, verified by urine cotinine levels above 100 ng/ml -lifetime history of e-cigarette use; in good health as verified by medical history -screening examination, and screening laboratory tests
- women, -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
- risk factors for EVALI (E-cigarette or Vaping Product Use-Associated Lung Injury) including history of lung diseases (e.g., asthma or COPD), vaping THC or CBD
- regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics)
- current alcohol or substance use disorder for any other recreational or prescription drugs other than nicotine
- for women, pregnant as determined by pregnancy screening, or breast feeding
- seeking (or undergoing) treatment for tobacco dependence or smoking; reported aversion to e-cigarettes, or tobacco flavored e-liquid.
Trial locations and contacts
1 site in 1 country.
About this study
This project will examine the impact of the nicotine dose and delivery rate on nicotine's abuse potential, versus its potentially beneficial effects on smoking urges and withdrawal. Will use pulsed IV nicotine administration which closely matches nicotine delivery by inhaled tobacco use.
Read the detailed description
Seventy smokers will be randomized to nicotine doses of either 0.2 or 1 mg per 70 kg body weight. Across 5 test sessions, within each dose group, participants will be randomly assigned to a sequence of 5 treatment conditions: placebo (saline) and 4 different delivery rates of nicotine. In each session, participants will receive either nicotine- or saline-pulsed infusions that will be delivered every 30 seconds for a total of 10 pulsed infusions. While receiving the pulsed infusions, participants will inhale a tobacco-flavored EC without nicotine, which will allow for a closer matching of the sensory aspects of inhaled tobacco use. There are four pulse duration conditions for the nicotine sessions: 2-, 4-, 6- and 8-second pulses. For those assigned to 1.0 mg/70kg nicotine dose, the pulse duration conditions correspond to nicotine delivery rates of 50, 25, 16.6, and 12.5 mcg nicotine/second. For those assigned to 0.2 mg/70 kg dose, the corresponding delivery rates will be 10, 5, 3.3 and 2.5 mcg nicotine/second. Participants in both nicotine dose groups will each have one placebo test session wherein they will receive 10 pulsed-saline infusions.
- Conditions
- Nicotine Dependence
- Being tested
- low dose Nicotine, high dose Nicotine
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
low dose NicotineDrug
Also called IV nicotine 1mg/70kg
IV nicotine infused over different delivery rates
high dose NicotineDrug
Also called IV Nicotine 0.2/70kg
IV Nicotine infused over different delivery rates
| Study group | Role | What they receive |
|---|---|---|
| delivery rate for nicotine dose 1mg/70kg | Active comparator | delivery rate 50,35, 16.6 and 12.5 ug per second Receives: Drug: low dose Nicotine |
| Delivery rate for nicotine dose 0.2mg/70kg | Active comparator | delivery rate 10,5, 3.3 and 2.5 Receives: Drug: high dose Nicotine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drug Effects Questionnaire mean score
The DEQ measures Good Drug Effect and consists of 11 questions with total score range from 0-100. Higher scores indicate more positive effects.
Measured: up to five years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2022
- Study start9 Sep 2022
- Primary completion8 Oct 2025
- Study completion8 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nicotine DependenceStudies 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
- Model description
- This will be a double-blind, placebo-controlled study employing a mixed design: nicotine dose as the between-subject and delivery rate as the within-subject factors.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mehmet Sofuoglu, Yale University
- Investigators
- Mehmet Sofuoglu, M.D.,Ph.D, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05176418
- Sponsor's protocol ID
- HIC 2000032210
- Status last verified
- Jun 2026
- First submitted
- 19 Nov 2021
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IV Pulsed-Nicotine as a Model of Smoking: The Effects of Dose and Delivery Rate
- ClinicalTrials.gov ID
- NCT05176418
- Acronym / sponsor ID
- HIC 2000032210
- Conditions
- Nicotine Dependence
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 9 Sep 2022 (actual)
- Primary completion
- 8 Oct 2025 (actual)
- Study completion
- 8 Oct 2025 (actual)
- First posted
- 4 Jan 2022 (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.
This project will examine the impact of the nicotine dose and delivery rate on nicotine's abuse potential, versus its potentially beneficial effects on smoking urges and withdrawal. Will use pulsed IV nicotine administration which closely matches nicotine delivery by inhaled tobacco use.
Detailed description
Seventy smokers will be randomized to nicotine doses of either 0.2 or 1 mg per 70 kg body weight. Across 5 test sessions, within each dose group, participants will be randomly assigned to a sequence of 5 treatment conditions: placebo (saline) and 4 different delivery rates of nicotine. In each session, participants will receive either nicotine- or saline-pulsed infusions that will be delivered every 30 seconds for a total of 10 pulsed infusions. While receiving the pulsed infusions, participants will inhale a tobacco-flavored EC without nicotine, which will allow for a closer matching of the sensory aspects of inhaled tobacco use. There are four pulse duration conditions for the nicotine sessions: 2-, 4-, 6- and 8-second pulses. For those assigned to 1.0 mg/70kg nicotine dose, the pulse duration conditions correspond to nicotine delivery rates of 50, 25, 16.6, and 12.5 mcg nicotine/second. For those assigned to 0.2 mg/70 kg dose, the corresponding delivery rates will be 10, 5, 3.3 and 2.5 mcg nicotine/second. Participants in both nicotine dose groups will each have one placebo test session wherein they will receive 10 pulsed-saline infusions.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- This will be a double-blind, placebo-controlled study employing a mixed design: nicotine dose as the between-subject and delivery rate as the within-subject factors.
| Arm | Type | Receives |
|---|---|---|
| delivery rate for nicotine dose 1mg/70kg | Active comparator | Drug: low dose Nicotinedelivery rate 50,35, 16.6 and 12.5 ug per second |
| Delivery rate for nicotine dose 0.2mg/70kg | Active comparator | Drug: high dose Nicotinedelivery rate 10,5, 3.3 and 2.5 |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Female and male, aged 21 to 55 years;
- past year daily cigarette use, verified by urine cotinine levels above 100 ng/ml -lifetime history of e-cigarette use; in good health as verified by medical history -screening examination, and screening laboratory tests
- women, -using acceptable birth control methods.
Key exclusion criteria (6 listed)
- History of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the participant to be in the study
- risk factors for EVALI (E-cigarette or Vaping Product Use-Associated Lung Injury) including history of lung diseases (e.g., asthma or COPD), vaping THC or CBD
- regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics)
- current alcohol or substance use disorder for any other recreational or prescription drugs other than nicotine
- for women, pregnant as determined by pregnancy screening, or breast feeding
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 |
|---|---|---|
| low dose NicotineAlso: IV nicotine 1mg/70kgIV nicotine infused over different delivery rates | Drug | delivery rate for nicotine dose 1mg/70kg |
| high dose NicotineAlso: IV Nicotine 0.2/70kgIV Nicotine infused over different delivery rates | Drug | Delivery rate for nicotine dose 0.2mg/70kg |
Primary outcome
Drug Effects Questionnaire mean score
Time frame: up to five years
The DEQ measures Good Drug Effect and consists of 11 questions with total score range from 0-100. Higher scores indicate more positive effects.
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 Jun 2026.
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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.
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 Early Phase 1 study testing low dose Nicotine and high dose Nicotine in people with Nicotine Dependence, 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 6 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 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. 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?
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?
Drug Effects Questionnaire mean score (time frame: up to five years). 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 9 Jun 2026.