Low Nicotine Cigarettes Plus Electronic Cigarettes

Study Overview
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Brief Summary
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This study aims to determine the health effects of very low nicotine content in cigarettes, in conjunction with the availability of nicotine-containing electronic cigarettes (e-cigs) among smokers with mental health conditions (SMHC).

Detailed Description
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The specific objective of this study is to recruit a cohort of 240 current exclusive daily SMHC (diagnosed using the MINI International Neuropsychiatric Interview) and to measure a comprehensive battery of behavioral and health indicators at 4, 8, 12 and 16 weeks after being randomized to use either normal nicotine content (NNC) Spectrum cigarettes (11.6 mg nicotine/cigarette) or very low nicotine content (VLNC) Spectrum cigarettes (0.2 mg nicotine/cigarette) while also having access to an electronic cigarette (containing either 0 nicotine or high nicotine e-liquid) in a randomized double-blind, placebo-controlled, 2 by 2 design. All participants will be followed up with a study visit 4 weeks after the final randomized visit to identify whether they have continued to use e-cigs/cigarettes and to assess their motivation in smoking abstinence. Our central hypothesis is that key markers of harms to health (e.g. urinary NNAL, exhaled carbon monoxide, measures of addiction, and mental distress) will be significantly improved among SMHC who are provided VLNC cigarettes and high nicotine e-cigs.

Official Title
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Randomized Trial of Low Nicotine Cigarettes Plus Electronic Cigarettes in Smokers

Conditions
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Tobacco Dependence

Intervention / Treatment
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* Other: Normal Nicotine Content research cigarettes
* Other: High Nicotine e-cigarette
* Other: Very Low Nicotine Content research cigarettes
* Other: Zero Nicotine e-cigarette


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Smoke >5 cigarettes per day for at least the prior 12 months Smoke regular, filtered cigarettes or machine-rolled cigarettes with a filter Exhaled CO measurement of ≥ 6 parts per million at baseline No serious cigarette smoking quit attempt or use of any FDA-approved smoking cessation medication in the prior 30 days (includes any nicotine replacement, varenicline, bupropion [used specifically as a quitting aid]) No plans to quit smoking within the next 3 weeks Must be willing to both switch to a different type of cigarette that may contain a different amount of nicotine and to try an e-cig to substitute for some of their cigarettes Must be willing and able to respond to contacts from study staff or attend visits over the study period (not planning to move, not planning extended vacation, no planned surgeries) 9. Must meet lifetime diagnostic criteria for a current or lifetime unipolar or bipolar mood disorder (e.g. major depressive disorder, major depressive episode, manic episode, hypomanic episode, bipolar disorder), an anxiety disorder (e.g. panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, , agoraphobia, social anxiety disorder, generalized anxiety disorder), a psychotic disorder (e.g. mood disorder or other psychotic disorder), or an eating disorder (e.g. anorexia or bulimia) based on the MINI-International Neuropsychiatric Interview Standard (MINI) (version 7.0.2) Able to read and write in English Able to understand and give informed consent Access to a computer/smartphone with e-mail and a reliable internet connection Exclusion Criteria: Women who are pregnant and/or nursing or trying to become pregnant Unstable or significant medical condition in the past 3 months (e.g., recent heart attack or other serious heart condition, stroke, severe angina, high blood pressure [systolic >159 mmHg or diastolic >99 mmHg during screening) Respiratory diseases (e.g., exacerbations of asthma or COPD, require oxygen, require oral prednisone), kidney (e.g., dialysis) or liver disease (e.g., cirrhosis), severe immune system disorders (e.g., uncontrolled HIV/AIDS, multiple sclerosis symptoms) or any medical disorder/medication that may affect participant safety or biomarker data Uncontrolled mental illness or substance abuse, or inpatient treatment for these in the past 6 months Current suicide risk on clinical assessment (above low risk score (or ≥ 9) on MINI diagnostic interview suicide module during screening (34)) Use of any non-cigarette nicotine delivery product (e.g., pipe, cigar, dip, chew, snus, hookah, e-cig, strips or sticks, IQOS) in the past 7 days at screening Use of an e-cig for 5 or more days in the past 28 days or any use in the past 7 days at screening Use of marijuana or other illegal drugs/prescription drugs for non-medical use daily/almost daily or weekly in the past 3 months per NIDA Quick Screen Any known allergy to propylene glycol or vegetable glycerin Surgery requiring general anesthesia in the past 6 weeks Unwilling to remain on one flavor of cigarette (regular or menthol) for the duration of the trial Previous use of SPECTRUM research cigarettes in the past 6 months Other member of household currently participating in the study History of a seizure disorder or had a seizure in the past 12 months Currently taking or have taken medications prescribed to prevent seizures (such as Carbamazepine or Phenobarbital). Using seizure medications for off-label use (indications other than treatment for seizures) will not be included as an exclusion, these will be assessed on a case-by-case basis

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 X 2 factorial design
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NNC cigarettes + High Nicotine Containing E-cigarette<br>Participants are provided with normal nicotine content (NNC) cigarettes (11.6 mg nicotine/cigarette) plus e-cigarette with high nicotine e-liquid. | Other: Normal Nicotine Content research cigarettes<br>* Research cigarettes with 11.6 mg nicotine/cigarette.<br>Other: High Nicotine e-cigarette<br>* E-cigarette containing high nicotine e-liquid<br>|
| Experimental: NNC cigarettes + Zero Nicotine Containing E-cigarette<br>Participants are provided with normal nicotine content (NNC) cigarettes (11.6 mg nicotine/cigarette) plus e-cigarette with zero nicotine e-liquid. | Other: Normal Nicotine Content research cigarettes<br>* Research cigarettes with 11.6 mg nicotine/cigarette.<br>Other: Zero Nicotine e-cigarette<br>* E-cigarette containing zero nicotine e-liquid<br>|
| Experimental: VLNC cigarettes + High Nicotine Containing E-cigarette<br>Participants are provided with very low nicotine content (VLNC) cigarettes (0.2 mg nicotine/cigarette) plus e-cigarette with high nicotine e-liquid. | Other: High Nicotine e-cigarette<br>* E-cigarette containing high nicotine e-liquid<br>Other: Very Low Nicotine Content research cigarettes<br>* Research cigarettes with 0.2 mg nicotine/cigarette.<br>|
| Experimental: VLNC cigarettes + Zero Nicotine Containing E-cigarette<br>Participants are provided with very low nicotine content (VLNC) cigarettes (0.2 mg nicotine/cigarette) plus e-cigarette with zero nicotine e-liquid | Other: Very Low Nicotine Content research cigarettes<br>* Research cigarettes with 0.2 mg nicotine/cigarette.<br>Other: Zero Nicotine e-cigarette<br>* E-cigarette containing zero nicotine e-liquid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) | Measure of tobacco-specific nitrosamine | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exhaled Carbon Monoxide | Measure of cigarette smoke exposure | Week 16 | 
| Kessler-6 score | Measure of serious psychological distress | Week 16 | 
| Penn State Cigarette Dependence Index | Measure of cigarette dependence | Week 16 | 
| Penn State Electronic Cigarette Dependence Index | Measure of e-cigarette dependence | Week 16 | 
| Cigarette abstinence | No cigarette use in the past 7 days and exhaled carbon monoxide < 6ppm | Week 20 |