Clinical trial NCT04058717: Low Nicotine Cigarettes Plus Electronic Cigarettes
Official title: Randomized Trial of Low Nicotine Cigarettes Plus Electronic Cigarettes in Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tobacco Dependence
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2019-08-15
Enrollment: 88
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2 X 2 factorial design
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Urinary NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol)
timeFrame: Week 16
Secondary outcomes:
measure: Exhaled Carbon Monoxide
timeFrame: Week 16
measure: Kessler-6 score
timeFrame: Week 16
measure: Penn State Cigarette Dependence Index
timeFrame: Week 16
measure: Penn State Electronic Cigarette Dependence Index
timeFrame: Week 16
measure: Cigarette abstinence
timeFrame: Week 20
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State College of Medicine
state: Pennsylvania
Study officials:
affiliation: Penn State College of Medicine
name: Jonathan Foulds, PhD
role: PRINCIPAL_INVESTIGATOR
References: