Very Low-Nicotine Cigarettes in Smokers With SUD (VLNC)

September 24, 2021 updated by: Damaris J. Rohsenow, Ph.D., Brown University

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
250

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Rhode Island
      • Providence, Rhode Island, United States, 02912
        • Brown University's Center for Alcohol and Addiction Studies

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria::

  • 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)

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Very low nicotine content cigarettes
Cigarettes with Nicotine Yield 0.07 ± 0.02
Drug: Nicotine
Behavioral: behavioral counseling for smoking cessation
Brief session of Brief advice. Assess smoking and provide assistance with quitting via coping skills.
Active Comparator: Conventional nicotine content cigarettes
Cigarettes with Nicotine Yield 0.8 ± 0.15
Drug: Nicotine
Behavioral: behavioral counseling for smoking cessation
Brief session of Brief advice. Assess smoking and provide assistance with quitting via coping skills.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
6 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Total N'-nitrosonornicotine (NNAL)
Time Frame: 6 weeks
Urinary N'-nitrosonornicotine and its glucuronide provide a measure of metabolites of the tobacco-specific carcinogen N'-nitrosonornicotine
6 weeks
Number of cigarettes smoked per day
Time Frame: 6 weeks
Time Line Follow Back for tobacco use will assess self-reported number of cigarettes smoked each day
6 weeks
Number of substance use days
Time Frame: 6 months
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.
6 months
Change in Beck Depression Inventory
Time Frame: Baseline and 6 weeks
Beck Depression Inventory will be administered at baseline and 6 weeks to detect any change in depression scores from baseline
Baseline and 6 weeks
Total N'-nitrosonornicotine (NNN)
Time Frame: 6 weeks
Urinary N'-nitrosonornicotine and its glucuronide provide a measure of metabolites of the tobacco-specific carcinogen N'-nitrosonornicotine
6 weeks
3-hydroxypyrene (3-HOP)
Time Frame: 6 weeks
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
6 weeks
3-hydroxypropylmercapturic acid (3-HPMA)
Time Frame: 6 weeks
Urinary 3-hydroxypropylmercapturic acid (3-HPMA) provides a measure of a metabolite of the toxicant acrolein
6 weeks
Total urinary cotinine levels
Time Frame: 6 weeks
cotinine plus cotinine-glucuronide, assessed via urinalysis
6 weeks
duration of longest tobacco abstinence period
Time Frame: 6 weeks
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.
6 weeks
Questionnaire of Smoking Urges, Brief Form
Time Frame: 6 weeks
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.
6 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Minnesota Nicotine Withdrawal Scale
Time Frame: 6 weeks
ratings of 7 nicotine withdrawal symptoms will be combined to form a single score for withdrawal
6 weeks
Penn Alcohol Craving Scale
Time Frame: 6 weeks
Assessment of craving for alcohol over the previous week. Administered weekly for 6 weeks, the mean of the 6 weeks will be used as the outcome variable.
6 weeks
Drug Craving Questionnaire
Time Frame: 6 weeks
Adapted from Tiffany's Cocaine Craving Questionnaire to assess craving for any drugs over the previous week. Administered weekly for 6 weeks, the mean of the scores over 6 weeks will be used as the outcome variable.
6 weeks
Change in Contemplation Ladder
Time Frame: Baseline and 6 weeks
The 10-point Contemplation Ladder provides a single continuous measure of motivation to quit smoking. Change from baseline to 6 weeks will be used as the outcome.
Baseline and 6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Brown University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Damaris J Rohsenow, PhD, Brown University
  • Study Director: Rosemarie A Martin, PhD, Brown University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 12, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 15, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 21, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 28, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 24, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • R01DA034628-01A1 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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