Nicotine DependencePhase 2VLNCNCT01989507
Very Low-Nicotine Cigarettes in Smokers With SUD
A Phase 2 study testing Nicotine and behavioral counseling for smoking cessation in people with Nicotine Dependence, run by Brown University at 1 site in United States.
Trial summary
The purpose of this study is to determine the efficacy, acceptability and unintended consequences of very low nicotine content cigarettes (VLNCC) in smokers with current or past year substance use disorders (SUD). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- Nicotine and behavioral counseling for smoking cessation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to 31 May 2021
- Phase
- Phase 2
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnostic and Statistical Manual-5 criteria for current or past year substance use disorder
- smoke 10+ cigarettes/day for past 6 months
- zero breath alcohol, negative urine drug tests and a self-report of no drug use in the past 30 days on day of informed consent
- score of 4-8 on the Contemplation Ladder (individuals interested in quitting smoking someday and/or have thought about quitting)
Who cannot join
- active psychosis as evidenced by hallucinations or delusions
- actively quitting smoking or current use of any nicotine replacement or other smoking cessation treatment
- medication contraindications for smoking cessation (smoking cessation may change the bioavailability of antipsychotics, warfarin, theophylline and insulin)
- other medications that could affect smoking (naltrexone, buprenorphine, acamprosate, anti-seizure medications, disulfiram)
- if on psychotropic medications, not stabilized on psychotropic medications (i.e., anti-depressant, anti-anxiety or anti-manic medications changed within past 4 weeks)
- inability to understand informed consent in a test (true-false questions) on the key elements of the consent form
Trial locations and contacts
1 site in 1 country.
United States1 site
Brown University's Center for Alcohol and Addiction Studies
Providence, Rhode Island, 02912
About this study
Official title: Very Low-Nicotine Cigarettes in Smokers With SUD: Smoking, Substance Use Effects
The purpose of this study is to determine the efficacy, acceptability and unintended consequences of very low nicotine content cigarettes (VLNCC) in smokers with current or past year substance use disorders (SUD). The primary aim of this study is to determine whether 6 weeks of VLNCC compared to normal nicotine content cigarettes (NNCC) will result in more smoking cessation over 6 months and reduce cigarette use, cotinine, and biomarkers of toxicity. We will also assess the effects of VLNCC versus NNCC cigarettes on frequency of substance use and substance cravings (drugs and alcohol) because this is relevant to the safety of these products among smokers with SUD. Secondary aims are to study effects on cigarette craving, nicotine withdrawal and dependence, and depressed mood. Methods: Random assignment to VLNCC versus NNCC of up to 312 smokers with SUD will be balanced by gender, degree of tobacco dependence, and recent drug and alcohol use. All smokers will be provided with smoking counseling. Assessments over 6 months will assess effects both during the 6 weeks of using research cigarettes and after return to usual cigarettes. The importance is in determining the viability and safety of this public health strategy in terms of effects on both smoking and other substance use in a highly addicted population, which is essential to determine before the FDA implements this policy.
Read the detailed description
The 2009 passage of the Family Smoking Prevention and Tobacco Control Act (FSPTCA) gave the Food and Drug Administration (FDA) the authority to reduce levels of nicotine in cigarettes if appropriate for public health. This project addresses an area targeted for study by NIH and the FDA to assess the impact of products with reduced toxicity on tobacco use behaviors. Very-low nicotine content cigarettes (VLNCC) have been shown in some studies with smokers from the general population to reduce craving and withdrawal for tobacco relative to abstinence with little or no compensatory smoking, suggesting that a mandated reduction in the nicotine yield of cigarettes could substantially reduce smoking rates. This may be a particularly effective method of reducing smoking and smoking-related disease in special populations that have very high rates of tobacco dependence, such as people with substance use disorders (SUD). However, the consequences of this policy for smokers with SUD have not been investigated, and a call has gone out for studies of the safety of these products with vulnerable populations such as these. The purpose of this study is to determine the efficacy, acceptability and unintended consequences of VLNCC in smokers with SUD (current or past year) currently abstinent from hard drugs. The primary aims are to determine whether VLNCC will increase smoking cessation and reduce cigarette use, cotinine, and biomarkers of toxicity in smokers with SUD relative to baseline and to those randomized to a normal nicotine content cigarette (NNCC), and to determine any unintended effects of VLNCC on substance use and cravings to use substances so as to investigate safety. Secondary aims are to study effects on cigarette craving and nicotine withdrawal and dependence (mechanisms), and state depression (safety). A 2-group between-group by pre-post design will compare 6 weeks of VLNCC to NNCC; all smokers will also be provided with smoking counseling. Follow-up over 6 months will assess effects after return to usual cigarettes. The importance is in determining the viability and safety of this public health strategy in terms of effects on both smoking and other substance use in a highly addicted population, which is essential to determine before the FDA implements this policy.
- Conditions
- Nicotine Dependence
- Being tested
- Nicotine, behavioral counseling for smoking cessation
- Keywords
- tobacco smoking, smoking cessation, nicotine dependence, tobacco use disorder
- Medical subject headings
- Tobacco Use Disorder, Tobacco Smoking, Smoking Cessation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NicotineDrug
behavioral counseling for smoking cessationBehavioural
Brief session of Brief advice. Assess smoking and provide assistance with quitting via coping skills.
| Study group | Role | What they receive |
|---|---|---|
| Very low nicotine content cigarettes | Experimental | Cigarettes with Nicotine Yield 0.07 ± 0.02 Receives: Drug: Nicotine; Behavioral: behavioral counseling for smoking cessation |
| Conventional nicotine content cigarettes | Active comparator | Cigarettes with Nicotine Yield 0.8 ± 0.15 Receives: Drug: Nicotine; Behavioral: behavioral counseling for smoking cessation |
What is being measured
The primary outcome is the main question the study is designed to answer.
7-day point-prevalence smoking abstinence
self-report of past 7 days abstinence confirmed by expired carbon monoxide (CO) reading of 6 ppm or less
Measured: 6 weeks
Secondary outcomes (10)
Total N'-nitrosonornicotine (NNAL)
Urinary N'-nitrosonornicotine and its glucuronide provide a measure of metabolites of the tobacco-specific carcinogen N'-nitrosonornicotine
Measured: 6 weeks
Number of cigarettes smoked per day
Time Line Follow Back for tobacco use will assess self-reported number of cigarettes smoked each day
Measured: 6 weeks
Number of substance use days
Time Line Follow Back will assess self-reported number of days of drinking or drug use. Any days of either will be counted as a substance use day.
Measured: 6 months
Change in Beck Depression Inventory
Beck Depression Inventory will be administered at baseline and 6 weeks to detect any change in depression scores from baseline
Measured: Baseline and 6 weeks
Total N'-nitrosonornicotine (NNN)
Urinary N'-nitrosonornicotine and its glucuronide provide a measure of metabolites of the tobacco-specific carcinogen N'-nitrosonornicotine
Measured: 6 weeks
3-hydroxypyrene (3-HOP)
Urinary 3-hydroxypyrene and its glucuronide and sulfate provides a measure of a metabolite of pyrene, a biomarker for uptake of carcinogenic polycyclic aromatic hydrocarbons
Measured: 6 weeks
3-hydroxypropylmercapturic acid (3-HPMA)
Urinary 3-hydroxypropylmercapturic acid (3-HPMA) provides a measure of a metabolite of the toxicant acrolein
Measured: 6 weeks
Total urinary cotinine levels
cotinine plus cotinine-glucuronide, assessed via urinalysis
Measured: 6 weeks
duration of longest tobacco abstinence period
Time Line Follow Back (TLFB) for tobacco use will be used to record self-reported tobacco abstinence each day. The longest number of contiguous abstinence days will be recorded.
Measured: 6 weeks
Questionnaire of Smoking Urges, Brief Form
Questionnaire of Smoking Urges, Brief Form assesses strong desire/intention to smoke and anticipating negative-affect relief from smoking. The total score from the 10 items will be used.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2013 (estimated)
- Study startApr 2014
- Primary completion31 May 2021
- Study completion31 May 2021
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 Brown 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 250 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Damaris J. Rohsenow, Ph.D., Brown University
- Investigators
- Damaris J Rohsenow, PhD, Principal investigator, Brown UniversityRosemarie A Martin, PhD, Study director, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01989507
- Sponsor's protocol ID
- R01DA034628-01A1
- Acronym
- VLNC
- Status last verified
- Sep 2021
- First submitted
- 12 Nov 2013
- Last updated
- 28 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Very Low-Nicotine Cigarettes in Smokers With SUD: Smoking, Substance Use Effects
- ClinicalTrials.gov ID
- NCT01989507
- Acronym / sponsor ID
- VLNC / R01DA034628-01A1
- Conditions
- Nicotine Dependence
- Keywords
- tobacco smoking, smoking cessation, nicotine dependence, tobacco use disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 250 participants (actual)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Study start
- Apr 2014 (actual)
- Primary completion
- 31 May 2021 (actual)
- Study completion
- 31 May 2021 (actual)
- First posted
- 21 Nov 2013 (estimated)
- 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.
The purpose of this study is to determine the efficacy, acceptability and unintended consequences of very low nicotine content cigarettes (VLNCC) in smokers with current or past year substance use disorders (SUD). The primary aim of this study is to determine whether 6 weeks of VLNCC compared to normal nicotine content cigarettes (NNCC) will result in more smoking cessation over 6 months and reduce cigarette use, cotinine, and biomarkers of toxicity. We will also assess the effects of VLNCC versus NNCC cigarettes on frequency of substance use and substance cravings (drugs and alcohol) because this is relevant to the safety of these products among smokers with SUD. Secondary aims are to study effects on cigarette craving, nicotine withdrawal and dependence, and depressed mood. Methods: Random assignment to VLNCC versus NNCC of up to 312 smokers with SUD will be balanced by gender, degree of tobacco dependence, and recent drug and alcohol use. All smokers will be provided with smoking counseling. Assessments over 6 months will assess effects both during the 6 weeks of using research cigarettes and after return to usual cigarettes. The importance is in determining the viability and safety of this public health strategy in terms of effects on both smoking and other substance use in a highly addicted population, which is essential to determine before the FDA implements this policy.
Detailed description
The 2009 passage of the Family Smoking Prevention and Tobacco Control Act (FSPTCA) gave the Food and Drug Administration (FDA) the authority to reduce levels of nicotine in cigarettes if appropriate for public health. This project addresses an area targeted for study by NIH and the FDA to assess the impact of products with reduced toxicity on tobacco use behaviors. Very-low nicotine content cigarettes (VLNCC) have been shown in some studies with smokers from the general population to reduce craving and withdrawal for tobacco relative to abstinence with little or no compensatory smoking, suggesting that a mandated reduction in the nicotine yield of cigarettes could substantially reduce smoking rates. This may be a particularly effective method of reducing smoking and smoking-related disease in special populations that have very high rates of tobacco dependence, such as people with substance use disorders (SUD). However, the consequences of this policy for smokers with SUD have not been investigated, and a call has gone out for studies of the safety of these products with vulnerable populations such as these. The purpose of this study is to determine the efficacy, acceptability and unintended consequences of VLNCC in smokers with SUD (current or past year) currently abstinent from hard drugs. The primary aims are to determine whether VLNCC will increase smoking cessation and reduce cigarette use, cotinine, and biomarkers of toxicity in smokers with SUD relative to baseline and to those randomized to a normal nicotine content cigarette (NNCC), and to determine any unintended effects of VLNCC on substance use and cravings to use substances so as to investigate safety. Secondary aims are to study effects on cigarette craving and nicotine withdrawal and dependence (mechanisms), and state depression (safety). A 2-group between-group by pre-post design will compare 6 weeks of VLNCC to NNCC; all smokers will also be provided with smoking counseling. Follow-up over 6 months will assess effects after return to usual cigarettes. The importance is in determining the viability and safety of this public health strategy in terms of effects on both smoking and other substance use in a highly addicted population, which is essential to determine before the FDA implements this policy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Very low nicotine content cigarettes | Experimental | Drug: Nicotine, Behavioral: behavioral counseling for smoking cessationCigarettes with Nicotine Yield 0.07 ± 0.02 |
| Conventional nicotine content cigarettes | Active comparator | Drug: Nicotine, Behavioral: behavioral counseling for smoking cessationCigarettes with Nicotine Yield 0.8 ± 0.15 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnostic and Statistical Manual-5 criteria for current or past year substance use disorder
- smoke 10+ cigarettes/day for past 6 months
- zero breath alcohol, negative urine drug tests and a self-report of no drug use in the past 30 days on day of informed consent
- score of 4-8 on the Contemplation Ladder (individuals interested in quitting smoking someday and/or have thought about quitting)
Key exclusion criteria (6 listed)
- active psychosis as evidenced by hallucinations or delusions
- actively quitting smoking or current use of any nicotine replacement or other smoking cessation treatment
- medication contraindications for smoking cessation (smoking cessation may change the bioavailability of antipsychotics, warfarin, theophylline and insulin)
- other medications that could affect smoking (naltrexone, buprenorphine, acamprosate, anti-seizure medications, disulfiram)
- if on psychotropic medications, not stabilized on psychotropic medications (i.e., anti-depressant, anti-anxiety or anti-manic medications changed within past 4 weeks)
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 | Drug | Conventional nicotine content cigarettes, Very low nicotine content cigarettes |
| behavioral counseling for smoking cessationBrief session of Brief advice. Assess smoking and provide assistance with quitting via coping skills. | Behavioural | Conventional nicotine content cigarettes, Very low nicotine content cigarettes |
Primary outcome
7-day point-prevalence smoking abstinence
Time frame: 6 weeks
self-report of past 7 days abstinence confirmed by expired carbon monoxide (CO) reading of 6 ppm or less
10 secondary outcomes
Total N'-nitrosonornicotine (NNAL)
Time frame: 6 weeks
Number of cigarettes smoked per day
Time frame: 6 weeks
Number of substance use days
Time frame: 6 months
Change in Beck Depression Inventory
Time frame: Baseline and 6 weeks
Total N'-nitrosonornicotine (NNN)
Time frame: 6 weeks
3-hydroxypyrene (3-HOP)
Time frame: 6 weeks
3-hydroxypropylmercapturic acid (3-HPMA)
Time frame: 6 weeks
Total urinary cotinine levels
Time frame: 6 weeks
duration of longest tobacco abstinence period
Time frame: 6 weeks
Questionnaire of Smoking Urges, Brief Form
Time frame: 6 weeks
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 28 Sep 2021.
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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.
Damaris J Rohsenow, PhD principal investigator
Brown University
Rosemarie A Martin, PhD study director
Brown University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nicotine and behavioral counseling for smoking cessation in people with Nicotine Dependence, run by Brown 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 4 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 28 Sep 2021. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
7-day point-prevalence smoking abstinence (time frame: 6 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 28 Sep 2021.