Nicotine DependenceEarly Phase 1NCT04535362

Nicotine's Potential Abuse With Menthol

A Early Phase 1 study testing Nicotine in people with Nicotine Dependence, run by Yale University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

To examine if switching from menthol to non-menthol cigarettes will change the dose-effect curves for positive subjective effects and alleviation of smoking urges as a function of nicotine delivery rate in smokers. Read more about this study

Who is it for?: Ages 21 to 35 years
Conditions the study is for: Nicotine Dependence
What is being tested?: Nicotine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 1 siteUnited States
Study dates: 28 Jun 2021to 29 Jun 2023
Phase: Early Phase 1
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 21 to 35 years
All sexes
No healthy volunteers
Adult

Who may be able to join

1) Female and male smokers, aged 21 to 35 years, who have been smoking tobacco cigarettes for at least a year;
2) smoke ≥ 5 and less than 20 cigarettes per day;
3) urine cotinine levels > 100 ng/mL consistent with nicotine intake of an active smoker
4) not seeking treatment at the time of the study for nicotine dependence;
5) in good health as verified by medical history, screening examination, and screening laboratory tests;
6) for women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.

Who cannot join

1) history of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the subject to be in the study;
2) regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics);
3) current alcohol or substance dependence for any other recreational or prescription drugs other than nicotine;
4) use of e-cigarettes more than 10 days in the past 30 days;
5) urine drug screening indicating recent illicit drugs use (with the exception of marijuana).

Trial locations and contacts

1 site in 1 country.

United States1 site

Department of Veterans Affairs Hospital
West Haven, Connecticut, 06516

Other trials in United States

About this study

Official title: Impact of Menthol on the Abuse Potential of Nicotine

Read the detailed description

A placebo-controlled study that will recruit male and female menthol nicotine dependent smokers. Following screening and evaluation as described above, eligible participants will be enrolled in the study which will last about 4 weeks. Eligible, participants will be randomized to menthol or non-menthol smoking condition for 2 weeks (Phase 1) and then will be switched to the alternative condition for another 2 weeks (Phase 2). The smoking condition will be open label. Participants will be provided with free cigarettes in Phases 1 and 2. For the menthol condition, participants will be provided their usual brand of menthol cigarettes and for the non-menthol condition, they will be provided a matched-brand non-menthol cigarette (e.g., Newport Non-Menthol Gold 100s for those who smoke Newport Menthol Gold 100s). In week 2 of each Phase, participants will have a test session. Each session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes. Once the participants complete the test session, participants will be crossed-over to the alternative treatment. The period between the 2 Phases will not be longer than one week.

Conditions: Nicotine Dependence
Being tested: 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.

NicotineDrug
Also called intravenous nicotine
session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes.

Study groups in NCT04535362
Study group	Role	What they receive
menthol cigarettes	Active comparator	Will smoke only menthol cigarettes for two weeks Receives: Drug: Nicotine
non menthol cigarettess	Active comparator	Will only smoke non menthol cigarettes for two weeks Receives: Drug: Nicotine

What is being measured

The primary outcome is the main question the study is designed to answer.

Drug Effect Questionnaire - Stimulatory Effects
Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.
Measured: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes
Drug Effect Questionnaire - Pleasure Effect
Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.
Measured: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes
Drug Effect Questionnaire - Aversive Effect
Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.
Measured: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes
Drug Effect Questionnaire - Head Rush
Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on all subscales, including Head Rush scale, range from 0 - 100 where lower scores indicate less head rush.
Measured: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes

Secondary outcomes (1)

SAFTEE
The SAFTEE is a technique for the systematic assessment of side effects in clinical trials developed by National Institute of Mental Health. It is a questionnaire that rates the current severity of a wide range of somatic, behavioral and affective symptoms in general and specific inquiry formats. It is designed to report adverse health events, regardless of whether or not they are suspected to be drug related, in order to reduce the under-reporting of unanticipated events compared with "known or expected" events.
Measured: up to one year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Jun 202129 Jun 2023

First posted1 Sep 2020
Study start28 Jun 2021
Primary completion29 Jun 2023
Study completion29 Jun 2023

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: Early Phase 1
Primary purpose: Health services research
Allocation: Randomised
Intervention model: Crossover
Model description: subjects will be unblinded to smoking menthol or non menthol for two weeks before each test session. Each session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes. Once the participants complete the test session, participants will be crossed-over to the alternative treatment.
Masking: Single blind
Who is masked: Participant
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04535362
Sponsor's protocol ID: 2000029223
Other IDs: 2U54DA036151-06
Status last verified: Aug 2024
First submitted: 24 Aug 2020
Last updated: 26 Aug 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Nicotine Dependence trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Impact of Menthol on the Abuse Potential of Nicotine
ClinicalTrials.gov ID: NCT04535362
Acronym / sponsor ID: 2000029223
Conditions: Nicotine Dependence
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: 28 Jun 2021 (actual)
Primary completion: 29 Jun 2023 (actual)
Study completion: 29 Jun 2023 (actual)
First posted: 1 Sep 2020 (actual)
Results: Posted 26 Aug 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Health services research
Allocation: Randomised
Intervention model: Crossover
Masking: Single blind (participant)
Number of arms: 2
Model description: subjects will be unblinded to smoking menthol or non menthol for two weeks before each test session. Each session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes. Once the participants complete the test session, participants will be crossed-over to the alternative treatment.

Arm	Type	Receives
menthol cigarettes	Active comparator	Drug: NicotineWill smoke only menthol cigarettes for two weeks
non menthol cigarettess	Active comparator	Drug: NicotineWill only smoke non menthol cigarettes for two weeks

Who may qualify

Ages: 21 to 35 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (6 listed)

1) Female and male smokers, aged 21 to 35 years, who have been smoking tobacco cigarettes for at least a year;
2) smoke ≥ 5 and less than 20 cigarettes per day;
3) urine cotinine levels > 100 ng/mL consistent with nicotine intake of an active smoker
4) not seeking treatment at the time of the study for nicotine dependence;
5) in good health as verified by medical history, screening examination, and screening laboratory tests;

Key exclusion criteria (5 listed)

1) history of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the subject to be in the study;
2) regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics);
3) current alcohol or substance dependence for any other recreational or prescription drugs other than nicotine;
4) use of e-cigarettes more than 10 days in the past 30 days;
5) urine drug screening indicating recent illicit drugs use (with the exception of marijuana).

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
NicotineAlso: intravenous nicotinesession will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes.	Drug	menthol cigarettes, non menthol cigarettess

Primary outcome

Drug Effect Questionnaire - Stimulatory Effects
Time frame: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes
Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.
Drug Effect Questionnaire - Pleasure Effect
Time frame: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes
Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.
Drug Effect Questionnaire - Aversive Effect
Time frame: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes
Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on the subscales range from 0 - 100 where 0 is the measure of least impactful 'effect'.
Drug Effect Questionnaire - Head Rush
Time frame: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes
Drug Effects Questionnaire was used to assess participants. The DEQ is consist of 10 items measured on a 1 to 100 visual analog scale, ranging from "not at all" to "extremely.". These ratings were then averaged to create three domain scores reflecting: 1) stimulatory effects (average of "feel stimulated", "feel drug effects" and "feel high"), 2) pleasurable effects (average of "like", "feel good " and "want more"), and 3) aversive effects (average of "feel anxious", "feel down" and "feel bad"). Head rush was also assessed. Scores on all subscales, including Head Rush scale, range from 0 - 100 where lower scores indicate less head rush.

1 secondary outcome

SAFTEE
Time frame: up to one year

Results and safety

Results posted to the registry on 26 Aug 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Menthol FIRST, Non-Menthol SECOND	8	5
Non-Menthol FIRST, Menthol SECOND	8	7

Primary outcome: Drug Effect Questionnaire - Stimulatory Effects

Time frame: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes. Mean (Standard Deviation). Unit: units on a scale

Measure	Menthol n = 16	Non-Menthol n = 13
2.5 Minutes	39.37 (24.41)	33.48 (19.73)
5 minutes	32.35 (27.93)	33.23 (28.79)
10 minutes	13.19 (16.15)	19.43 (21.41)

Menthol vs Non-Menthol: Mean Difference (Net): 0.05, p = 0.93, Mixed Models Analysis

Population analysed: Participants assessed an any or both points in the crossover design.

Primary outcome: Drug Effect Questionnaire - Pleasure Effect

Time frame: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes. Mean (Standard Deviation). Unit: units on a scale

Measure	Menthol n = 16	Non-Menthol n = 13
2.5 minutes	37.51 (28.35)	27.25 (17.62)
5 minutes	36.49 (31.55)	29.28 (25.42)
10 minutes	23.42 (20.80)	24.71 (18.37)

Menthol vs Non-Menthol: Mean Difference (Net): 0.12, p = 0.68, Mixed Models Analysis

Population analysed: Participants assessed an any or both points in the crossover design.

Primary outcome: Drug Effect Questionnaire - Aversive Effect

Time frame: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes. Mean (Standard Deviation). Unit: units on a scale

Measure	Menthol n = 16	Non-Menthol n = 13
2.5 minutes	11.33 (11.78)	14.76 (15.56)
5 minutes	8.73 (11.12)	11.23 (13.78)
10 minutes	6.33 (8.50)	6.92 (8.79)

Menthol vs Non-Menthol: Mean Difference (Net): 0.46, p = 0.37, Mixed Models Analysis

Population analysed: Participants assessed an any or both points in the crossover design.

Primary outcome: Drug Effect Questionnaire - Head Rush

Time frame: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes. Mean (Standard Deviation). Unit: units on a scale

Measure	Menthol n = 16	Non-Menthol n = 13
2.5 minutes	31.73 (32.55)	14.76 (15.56)
5 minutes	19.20 (25.48)	11.23 (13.78)
10 minutes	8.93 (13.93)	6.92 (8.79)

Menthol vs Non-Menthol: Mean Difference (Net): 1.26, p = 0.20, Mixed Models Analysis

Population analysed: Participants assessed an any or both points in the crossover design.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 4 weeks total (2 sessions of 2 week smoking periods) - each with 2 3 hour sessions.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Menthol	0 of 16 (0%)	0 of 16 (0%)	0 of 16
Non-Menthol	0 of 13 (0%)	0 of 13 (0%)	0 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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 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 6 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 26 Aug 2024. 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?

Yes. Results are posted in the registry (first posted 26 Aug 2024). 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 Effect Questionnaire - Stimulatory Effects (time frame: Following 2 weeks of smoking, the procedure took over 3 hours, with measured effects at 2.5 minutes, 5 minutes and 10 minutes). The study lists 4 primary outcomes in all. 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 NCT04535362.

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 26 Aug 2024.