Project 2, Study 2: Extended Exposure to Low Nicotine Content Cigarettes in Opioid Abusers (P2S2)

• ClinicalTrials.gov Identifier: NCT02250664
• Recruitment Status: Completed
• First Posted: September 26, 2014
• Last Update Posted: June 11, 2020
• Sponsor: University of Vermont
• Collaborators: National Institute on Drug Abuse (NIDA); Johns Hopkins University
• Information provided by (Responsible Party): Stephen T. Higgins, PhD, University of Vermont

Study Description

Brief Summary:

This study will examine extended exposure to cigarettes varying in nicotine content among opioid abusers. Prevalence of smoking among opioid-dependent adults far exceeds that of the general US adult population. Opioid-dependent smokers are also at elevated risk for smoking-related adverse health effects. Studies testing an innovative regulatory strategy of reducing the nicotine content of cigarettes to a non-addictive level have shown promising beneficial effects (decreased smoking rate, reduced toxicant exposure, and increased cessation) in the general population of smokers. However, these studies have uniformly excluded vulnerable populations like opioid abusers who may respond differently considering their greater vulnerability to smoking and nicotine dependence. Thus, little is known scientifically about how this highly vulnerable subgroup of smokers might respond to a nicotine reduction policy. This project is designed to address that substantial knowledge gap.

Condition or disease	Intervention/treatment	Phase
Tobacco Use Disorder	Other: Very low nicotine content cigarettes	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 282 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Project 2, Study 2: Extended Exposure to Low Nicotine Content Cigarettes in Opioid Abusers
• Study Start Date: October 2016
• Actual Primary Completion Date: October 2019
• Actual Study Completion Date: October 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: 0.8 mg nicotine; 0.8 mg nicotine very low nicotine content cigarettes	Other: Very low nicotine content cigarettes; Very low nicotine content cigarettes
Experimental: 0.12 mg nicotine; 0.12 mg nicotine very low nicotine content cigarettes	Other: Very low nicotine content cigarettes; Very low nicotine content cigarettes
Experimental: 0.03 mg nicotine; 0.03 mg nicotine very low nicotine content cigarettes	Other: Very low nicotine content cigarettes; Very low nicotine content cigarettes

Outcome Measures

Primary Outcome Measures :

1. Cigarettes per day [ Time Frame: 12 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Men and women ages 18-70, who are currently receiving methadone or buprenorphine maintenance treatment for opioid dependence.
2. Report smoking ≥ 5 cigarettes per day.
3. Provide an intake breath CO sample >8 ppm.
4. Be without current (within the past year) serious mental disorder that would interfere with study results or completion as determined by the licensed medical professional or PI.
5. Be sufficiently literate to complete the research-related tasks.
6. Be in good physical health without serious illness or change in health or medication (not including methadone or buprenorphine dose) in the past three months as determined by the license medical professional at each site.
7. Not pregnant or nursing, and report using oral, implant, injection or barrier contraceptives, or report being surgically sterile, or post menopausal.
8. Report no significant use of other tobacco or nicotine products within the past month (more than 9 days in the past 30).

9. Participants must be maintained on a stable methadone or buprenorphine dose for the past month, with no evidence of regular illicit-drug abuse (<30% positive specimens in the past 30 days).

   1. Consent to confirm dose and drug abstinence with the participant's opioid clinic will be obtained at screening and we will monitor any changes in dose throughout the study.
   2. Participants must provide at least three urine samples within the last 30 days. If they do not have three they will be asked to come in and provide a sample. They may leave up to two samples per week with at least one full day between samples.

Exclusion Criteria:

1. Any prior regular use (used as primary cigarette outside of laboratory) of Spectrum cigarettes (i.e., research cigarettes with reduced nicotine content).
2. Exclusive use of roll-your-own cigarettes.
3. Planning to quit smoking in the next 30 days.
4. A quit attempt in the past 30 days resulting in greater than 3 days of abstinence.
5. Currently taking anticonvulsant medications.
6. Positive toxicology screen for illicit drugs not including Marijuana ( participants with valid prescriptions will not be excluded and participants with a positive toxicology screen will be allowed to re-screen once).
7. Not currently enrolled in a treatment program for opioid dependence and/or not currently stable on their methadone or buprenorphine dose.
8. Breath alcohol level > 0.01 ( participants with a positive screen will be allowed to re-screen once).
9. Self-report of binge drinking alcohol (more than 9 days in the past 30 days, 4/5 drinks in a 2 hour period in females/males),

10. Blood pressure is greater than or equal to 160/100 mmHg or below 90/50 mmHg (participants outside the range will be allowed to re-screen once).

    a. Participants failing for blood pressure will be allowed to re-screen once.

11. Breath CO > 80 ppm.
12. Heart rate is greater than or equal to 115 bpm or less than 45 bpm ( participants outside the range will be allowed to re-screen once).
13. Currently seeking treatment for smoking cessation.
14. Have used nicotine replacement, bupropion or other pharmacotherapies as cessation aids in the past month (bupropion will be allowed for treatment of depression).
15. Current symptoms of psychosis or dementia, or mania.
16. Suicidal ideation in the past month. 17.) Suicide attempt in the past 6 months. 18.) Participation in another research study in the past 30 days.

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21224

United States, Vermont

University of Vermont

Burlington, Vermont, United States, 05401

Sponsors and Collaborators

University of Vermont

National Institute on Drug Abuse (NIDA)

Johns Hopkins University

Investigators

• Study Director: Stephen T. Higgins, Ph.D.; University of Vermont
• Principal Investigator: Stacey Sigmon, Ph.D.; University of Vermont

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Oliver AC, DeSarno M, Irvin CG, Kaminsky D, Tidey JW, Sigmon SC, Heil SH, Gaalema DE, Lee D, Bunn JY, Davis DR, Streck JM, Gallagher T, Higgins ST. Effects of Reduced Nicotine Content Cigarettes on Fractional Exhaled Nitric Oxide and Self-Reported Respiratory Health Outcomes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage. Nicotine Tob Res. 2022 Jan 1;24(1):135-140. doi: 10.1093/ntr/ntab145.

Higgins ST, DeSarno M, Bunn JY, Gaalema DE, Leventhal AM, Davis DR, Streck JM, Harfmann RF, Markesich C, Orr E, Sigmon SC, Heil SH, Tidey JW, Lee D, Hughes JR. Cumulative vulnerabilities as a potential moderator of response to reduced nicotine content cigarettes. Prev Med. 2021 Nov;152(Pt 2):106714. doi: 10.1016/j.ypmed.2021.106714. Epub 2021 Jul 7.

Higgins ST, Tidey JW, Sigmon SC, Heil SH, Gaalema DE, Lee D, Hughes JR, Villanti AC, Bunn JY, Davis DR, Bergeria CL, Streck JM, Parker MA, Miller ME, DeSarno M, Priest JS, Cioe P, MacLeod D, Barrows A, Markesich C, Harfmann RF. Changes in Cigarette Consumption With Reduced Nicotine Content Cigarettes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage: 3 Randomized Clinical Trials. JAMA Netw Open. 2020 Oct 1;3(10):e2019311. doi: 10.1001/jamanetworkopen.2020.19311.

Higgins ST, DeSarno M, Davis DR, Nighbor T, Streck JM, Adise S, Harfmann R, Nesheim-Case R, Markesich C, Reed D, Tyndale RF, Gaalema DE, Heil SH, Sigmon SC, Tidey JW, Villanti AC, Lee D, Hughes JR, Bunn JY. Relating individual differences in nicotine dependence severity to underpinning motivational and pharmacological processes among smokers from vulnerable populations. Prev Med. 2020 Nov;140:106189. doi: 10.1016/j.ypmed.2020.106189. Epub 2020 Jul 3.

• Responsible Party: Stephen T. Higgins, PhD, Professor, University of Vermont
• ClinicalTrials.gov Identifier: NCT02250664
• Other Study ID Numbers: P50DA036114:P2S2; P50DA036114 ( U.S. NIH Grant/Contract )
• First Posted: September 26, 2014
• Last Update Posted: June 11, 2020
• Last Verified: October 2016

Keywords provided by Stephen T. Higgins, PhD, University of Vermont:

Biomarkers of exposure; Compensatory smoking; Nicotine dependence; Reduced nicotine cigarettes; Tobacco withdrawal; Women; Health disparities; Vulnerable populations

Additional relevant MeSH terms:

Tobacco Use Disorder; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Nicotine; Ganglionic Stimulants; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action