Nicotine DependenceNCT02102100
The Effects of Menthol as Delivered by an Electronic Cigarette on the Desirability of Nicotine in Tobacco Users
A study testing nicotine and menthol in people with Nicotine Dependence, run by Yale University at 2 sites in United States.
Trial summary
This study will help determine if menthol administered by inhalation via electronic cigarettes (e-cigarette) changes the reinforcing effects of pure nicotine administered intravenously in cigarette smokers who smoke mentholated or non-mentholated cigarettes. Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- nicotine and menthol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 2 sitesUnited States
- Study dates
- 26 Mar 2014to 11 Jul 2016
- Phase
- Interventional
- 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 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Female and male smokers, aged 18 to 30 years;
- History of smoking for the past 12 months, at least one cigarette per day; smoking status is verified with urinary cotinine levels above 10 ng/ml;
- Not seeking treatment for nicotine dependence at the time of study entry;
- In good health as verified by medical history, screening examination, and screening laboratory tests;
- For women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.
Who cannot join
- History of major medical illnesses that the physician investigator deems as contraindicated for the patient to be in the study
- Regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics);
- A psychiatric diagnosis and / or treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia or panic disorder in the past month
- Abuse of alcohol or any other recreational or prescription drugs in the past 30 days.
- Any allergy to propylene glycol or menthol.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Connecticut VA Healthcare System
West Haven, Connecticut, 06516
VA Connecticut Health Care System
West Haven, Connecticut, 06516
About this study
Official title: Menthol's Effects on Nicotine Reinforcement in Smokers
This study will help determine if menthol administered by inhalation via electronic cigarettes (e-cigarette) changes the reinforcing effects of pure nicotine administered intravenously in cigarette smokers who smoke mentholated or non-mentholated cigarettes.
Read the detailed description
Male and female smokers will be recruited from the New Haven area through newspaper advertisements, radio advertisements, and fliers. Interested subjects will have the study described over the telephone, and they will be asked to answer a brief tobacco use history and medical screening questionnaire. If subjects pass the telephone screening, they will be invited to come to the West Haven VA clinic for a screening evaluation. This screening evaluation will be for the menthol / nicotine reinforcement study as described in detail in this project description. The dose-finding study was conducted at the John B. Pierce Laboratory. The dose finding study concluded with the establishment of the high and low dose of menthol that will be used in this protocol "Menthol's Effects on Nicotine Reinforcement in Smokers." The screening of these subjects used the same inclusion and exclusion criteria as described below.
Inclusion criteria: Female and male smokers, aged 18 to 30 years; history of smoking for the past 12 months, at least one cigarette per day; smoking status is verified with urinary cotinine levels above 10 ng/ml; not seeking treatment for nicotine dependence at the time of study entry; in good health as verified by medical history, screening examination, and screening laboratory tests; for women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.
Exclusion criteria: History of major medical illnesses that the physician investigator deems as contraindicated for the patient to be in the study; regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics); psychiatric diagnosis and / or treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia or panic disorder in the past month and abuse of alcohol or any other recreational or prescription drugs in the past 30 days. Any allergy to propylene glycol or menthol.
This outpatient, double-blind, placebo-controlled study consisted of an adaptation session followed by three test sessions. All participants were randomized to a test session order and received control menthol (0.0% + tobacco flavor), low menthol (0.5% + tobacco flavor), and high menthol (3.2% + tobacco flavor) by standardized inhalation from an e-cigarette just prior to each nicotine infusion (a single menthol condition for each test session). Within each test session, all 3 IV nicotine conditions were tested, one hour apart, by delivering saline, nicotine at 0.25 mg nicotine/70 kg and nicotine at 0.5 mg nicotine/70 kg, in a random order, just after last inhalation. For each participant, the randomized nicotine infusion sequence was fixed across the three test sessions, each performed at least 24 hours apart.
- Conditions
- Nicotine Dependence
- Being tested
- nicotine, menthol
- Keywords
- menthol, electronic cigarette, nicotine, smoking, tobacco
- Medical subject headings
- Tobacco Use Disorder, Vaping, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nicotineDrug
In each of 3 test sessions, subjects in each arm will receive a randomized sequence of three intravenous infusions (30 sec each), one hour apart. The infusions will consist of saline, nicotine (.25 mg / 70kg) and nicotine (0.5 mg / 70 kg). The randomized sequence will remain the same between test sessions for a given subject.
mentholDrug
Also called racemic menthol
In each of 3 test sessions, subjects will take 6 inhalations from the study e-cigarette, one inhalation every 15 seconds, of the randomized menthol condition for that test session ust prior to each intravenous infusion. The menthol conditions are: 3.2% menthol, 0.5% menthol and tobacco-flavor only (0.0% menthol)
| Study group | Role | What they receive |
|---|---|---|
| Menthol-Preferring Smokers | Experimental | Each subject in this arm received a random sequence of 3 different inhaled menthol conditions across 3 test sessions (a single menthol condition for each test session). In each test session, a random order of one saline, and 2 nicotine (0.25 mg and 0.5 mg /70 kg) infusions were given one hour apart, concurrent with the randomized menthol inhalation condition for that test session. Receives: Drug: nicotine; Drug: menthol |
| Non-Menthol Preferring Smokers | Experimental | Each subject in this arm received a random sequence of 3 different inhaled menthol conditions across 3 test sessions (a single menthol condition for each test session). In each test session, a random order of one saline, and 2 nicotine (0.25 mg and 0.5 mg /70 kg) infusions were given one hour apart, concurrent with the randomized menthol inhalation condition for that test session. Receives: Drug: nicotine; Drug: menthol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drug Effects Questionnaire (DEQ)- 'Good Drug Effects'
The Drug Effects Questionnaire (DEQ) is used in studies of acute subjective response (SR) to a variety of substances. The DEQ consists of 11 questions: cooling effect, dislike the sensation, any sensations, feel a drug effect, high, feel stimulated, feel a head rush, like drug effect, dislike any effects, craving a cigarette, and like more of the drug. To calculate the DEQ- 'Good Drug Effects', peak values from post-infusion time points were calculated for the change in the intensity of positive subjective effects as measured with 2 DEQ questions - DEQ question #6 'like drug effect' and DEQ question #11 'would like more of the drug'. Each question was measured on a scale with a minimum score of 0 and a maximum score of 100.The peak values for "like" and " I want more" were averaged to obtain a summary score to represent the feel 'Good Drug Effects' composite factor. DEQ measures were skewed and square root transformations were used. Higher scores indicate more positive effects.
Measured: up to 55 minutes post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2014 (estimated)
- Study start26 Mar 2014
- Primary completion11 Jul 2016
- Study completion11 Jul 2016
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 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
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects in each of the 2 arms received a random sequence of 3 different inhaled menthol conditions across 3 test sessions (a single menthol condition for each test session). In each test session, a random order of one saline, and 2 nicotine (0.25 mg and 0.5 mg /70 kg) infusions were given one hour apart, concurrent with the randomized menthol inhalation condition for that test session. The randomized sequence of nicotine infusions was the same for each test session.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Mehmet Sofuoglu, Yale University
- Investigators
- Mehmet Sofuoglu, MD, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02102100
- Sponsor's protocol ID
- 1309012678
- Other IDs
- 1P50DA036151-01
- Status last verified
- Mar 2020
- First submitted
- 7 Oct 2013
- Last updated
- 19 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Menthol's Effects on Nicotine Reinforcement in Smokers
- ClinicalTrials.gov ID
- NCT02102100
- Acronym / sponsor ID
- 1309012678
- Conditions
- Nicotine Dependence
- Keywords
- menthol, electronic cigarette, nicotine, smoking, tobacco
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 26 Mar 2014 (actual)
- Primary completion
- 11 Jul 2016 (actual)
- Study completion
- 11 Jul 2016 (actual)
- First posted
- 2 Apr 2014 (estimated)
- Results
- Posted 20 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will help determine if menthol administered by inhalation via electronic cigarettes (e-cigarette) changes the reinforcing effects of pure nicotine administered intravenously in cigarette smokers who smoke mentholated or non-mentholated cigarettes.
Detailed description
Male and female smokers will be recruited from the New Haven area through newspaper advertisements, radio advertisements, and fliers. Interested subjects will have the study described over the telephone, and they will be asked to answer a brief tobacco use history and medical screening questionnaire. If subjects pass the telephone screening, they will be invited to come to the West Haven VA clinic for a screening evaluation. This screening evaluation will be for the menthol / nicotine reinforcement study as described in detail in this project description. The dose-finding study was conducted at the John B. Pierce Laboratory. The dose finding study concluded with the establishment of the high and low dose of menthol that will be used in this protocol "Menthol's Effects on Nicotine Reinforcement in Smokers." The screening of these subjects used the same inclusion and exclusion criteria as described below.
Inclusion criteria: Female and male smokers, aged 18 to 30 years; history of smoking for the past 12 months, at least one cigarette per day; smoking status is verified with urinary cotinine levels above 10 ng/ml; not seeking treatment for nicotine dependence at the time of study entry; in good health as verified by medical history, screening examination, and screening laboratory tests; for women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.
Exclusion criteria: History of major medical illnesses that the physician investigator deems as contraindicated for the patient to be in the study; regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics); psychiatric diagnosis and / or treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia or panic disorder in the past month and abuse of alcohol or any other recreational or prescription drugs in the past 30 days. Any allergy to propylene glycol or menthol.
This outpatient, double-blind, placebo-controlled study consisted of an adaptation session followed by three test sessions. All participants were randomized to a test session order and received control menthol (0.0% + tobacco flavor), low menthol (0.5% + tobacco flavor), and high menthol (3.2% + tobacco flavor) by standardized inhalation from an e-cigarette just prior to each nicotine infusion (a single menthol condition for each test session). Within each test session, all 3 IV nicotine conditions were tested, one hour apart, by delivering saline, nicotine at 0.25 mg nicotine/70 kg and nicotine at 0.5 mg nicotine/70 kg, in a random order, just after last inhalation. For each participant, the randomized nicotine infusion sequence was fixed across the three test sessions, each performed at least 24 hours apart.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Subjects in each of the 2 arms received a random sequence of 3 different inhaled menthol conditions across 3 test sessions (a single menthol condition for each test session). In each test session, a random order of one saline, and 2 nicotine (0.25 mg and 0.5 mg /70 kg) infusions were given one hour apart, concurrent with the randomized menthol inhalation condition for that test session. The randomized sequence of nicotine infusions was the same for each test session.
| Arm | Type | Receives |
|---|---|---|
| Menthol-Preferring Smokers | Experimental | Drug: nicotine, Drug: mentholEach subject in this arm received a random sequence of 3 different inhaled menthol conditions across 3 test sessions (a single menthol condition for each test session). In each test session, a random order of one saline, and 2 nicotine (0.25 mg and 0.5 mg /70 kg) infusions were given one hour apart, concurrent with the randomized menthol inhalation condition for that test session. |
| Non-Menthol Preferring Smokers | Experimental | Drug: nicotine, Drug: mentholEach subject in this arm received a random sequence of 3 different inhaled menthol conditions across 3 test sessions (a single menthol condition for each test session). In each test session, a random order of one saline, and 2 nicotine (0.25 mg and 0.5 mg /70 kg) infusions were given one hour apart, concurrent with the randomized menthol inhalation condition for that test session. |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Female and male smokers, aged 18 to 30 years;
- History of smoking for the past 12 months, at least one cigarette per day; smoking status is verified with urinary cotinine levels above 10 ng/ml;
- Not seeking treatment for nicotine dependence at the time of study entry;
- In good health as verified by medical history, screening examination, and screening laboratory tests;
- For women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.
Key exclusion criteria (5 listed)
- History of major medical illnesses that the physician investigator deems as contraindicated for the patient to be in the study
- Regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics);
- A psychiatric diagnosis and / or treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia or panic disorder in the past month
- Abuse of alcohol or any other recreational or prescription drugs in the past 30 days.
- Any allergy to propylene glycol or menthol.
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 |
|---|---|---|
| nicotineIn each of 3 test sessions, subjects in each arm will receive a randomized sequence of three intravenous infusions (30 sec each), one hour apart. The infusions will consist of saline, nicotine (.25 mg / 70kg) and nicotine (0.5 mg / 70 kg). The randomized sequence will remain the same between test sessions for a given subject. | Drug | Menthol-Preferring Smokers, Non-Menthol Preferring Smokers |
| mentholAlso: racemic mentholIn each of 3 test sessions, subjects will take 6 inhalations from the study e-cigarette, one inhalation every 15 seconds, of the randomized menthol condition for that test session ust prior to each intravenous infusion. The menthol conditions are: 3.2% menthol, 0.5% menthol and tobacco-flavor only (0.0% menthol) | Drug | Menthol-Preferring Smokers, Non-Menthol Preferring Smokers |
Primary outcome
Drug Effects Questionnaire (DEQ)- 'Good Drug Effects'
Time frame: up to 55 minutes post-infusion
The Drug Effects Questionnaire (DEQ) is used in studies of acute subjective response (SR) to a variety of substances. The DEQ consists of 11 questions: cooling effect, dislike the sensation, any sensations, feel a drug effect, high, feel stimulated, feel a head rush, like drug effect, dislike any effects, craving a cigarette, and like more of the drug. To calculate the DEQ- 'Good Drug Effects', peak values from post-infusion time points were calculated for the change in the intensity of positive subjective effects as measured with 2 DEQ questions - DEQ question #6 'like drug effect' and DEQ question #11 'would like more of the drug'. Each question was measured on a scale with a minimum score of 0 and a maximum score of 100.The peak values for "like" and " I want more" were averaged to obtain a summary score to represent the feel 'Good Drug Effects' composite factor. DEQ measures were skewed and square root transformations were used. Higher scores indicate more positive effects.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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. This study is not recruiting at the moment.
Mehmet Sofuoglu, MD, PhD principal investigator
Yale University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing nicotine and menthol in people with Nicotine Dependence, run by Yale University at 2 sites 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: finished, as of the sponsor's last update on 19 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 2 sites 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Feb 2019). 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?
Drug Effects Questionnaire (DEQ)- 'Good Drug Effects' (time frame: up to 55 minutes post-infusion). 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 19 Mar 2020.