NCT02232737

Project 3, Study 2: Extended Exposure to Low Nicotine Content Cigarettes in People With Current Affective Disorders

Completed Phase 1, PHASE2 Results posted Last updated 7 December 2022

What this trial tests

Phase 1, PHASE2 trial testing Very low nicotine content cigarettes in Tobacco Use Disorder in 775 participants. Completed in 14 January 2019.

Timeline

7 October 2016

Primary endpoint
14 January 2019

14 January 2019

Quick facts

Lead sponsor	Brown University
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	basic science
Enrollment	775
Start date	7 October 2016
Primary completion	14 January 2019
Estimated completion	14 January 2019
Sites	2 locations across United States

Drugs / interventions tested

• Very low nicotine content cigarettes — full drug profile →

Conditions studied

• Tobacco Use Disorder — all drugs for Tobacco Use Disorder →

Sponsor

Brown University

Who can join

Adults 18 to 70, any sex, with Tobacco Use Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cigarettes Per Day (CPD) Primary · 12 weeks

Participant reported number of cigarettes smoked per day at Week 12

Group	Value	95% CI
0.8 mg Nicotine	25.28	± 0.77
0.12 mg Nicotine	19.95	± 0.80
0.03 mg Nicotine	17.74	± 0.74

Adverse events — posted to ClinicalTrials.gov

Time frame: 12 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

0.8 mg Nicotine

Serious: 13/254 (5%)

Deaths: 0/254

0.12 mg Nicotine

Serious: 4/235 (2%)

Deaths: 1/235

0.03 mg Nicotine

Serious: 13/286 (5%)

Deaths: 1/286

Serious adverse events (14 terms)

Reaction	System	0.8 mg Nicotine	0.12 mg Nicotine	0.03 mg Nicotine
Kidney infection	Infections and infestations	—	—	—
Seizure	Nervous system disorders	—	—	—
Sudden onset of chest pain due to not enough blood going to the heart	Cardiac disorders	—	—	—
Broken bone	Injury, poisoning and procedural complications	—	—	—
Anxiety, feelings of dread or danger	Psychiatric disorders	—	—	—
Blurred vision	Eye disorders	—	—	—
Bloody stool	Gastrointestinal disorders	—	—	—
Frontal lobe lesion	Investigations	—	—	—
Diabetes Type 2	Metabolism and nutrition disorders	—	—	—
Tenosynovitis of the Hand	Musculoskeletal and connective tissue disorders	—	—	—
Acute renal failure	Renal and urinary disorders	—	—	—
Skin graft to wound on leg	Skin and subcutaneous tissue disorders	—	—	—
Neurosurgery	Surgical and medical procedures	—	—	—
High blood pressure	Vascular disorders	—	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	0.8 mg Nicotine	0.12 mg Nicotine	0.03 mg Nicotine
Infections and infestations	Infections and infestations	—	—	—
Respiratory, thoracic, and mediastinal disorders	Respiratory, thoracic and mediastinal disorders	—	—	—
Gastrointestinal disorders	Gastrointestinal disorders	—	—	—
General disorders	General disorders	—	—	—
Nervous system disorders	Nervous system disorders	—	—	—
Musculoskeletal and connective tissue disorders	Musculoskeletal and connective tissue disorders	—	—	—
Surgical and medical procedures	Surgical and medical procedures	—	—	—
Vascular disorders	Vascular disorders	—	—	—
Injury, poisoning, and procedural complications	Injury, poisoning and procedural complications	—	—	—

Most-reported serious reactions: Kidney infection, Seizure, Sudden onset of chest pain due to not enough blood going to the heart, Broken bone, Anxiety, feelings of dread or danger, Blurred vision, Bloody stool, Frontal lobe lesion.

Data from ClinicalTrials.gov NCT02232737 adverse events section.

Sponsor's own description

This study will examine extended exposure to cigarettes varying in nicotine content among disadvantaged women. Adults with affective disorders are at increased risk for smoking, nicotine dependence, and using high nicotine yield cigarettes and are also at significantly increased risk for smoking-related adverse health consequences, including site-specific cancers, heart disease, and premature death. 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 those with affective disorders 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. This same study was also conducted in two additional vulnerable populations under a similar protocol.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Changes in Cigarette Consumption With Reduced Nicotine Content Cigarettes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage: 3 Randomized Clinical Trials.
   Higgins ST, Tidey JW, Sigmon SC, Heil SH, et al · · 2020 · cited 61× · PMID 33079196 · DOI 10.1001/jamanetworkopen.2020.19311
2. Effects of 6-Week Use of Reduced-Nicotine Content Cigarettes in Smokers With and Without Elevated Depressive Symptoms.
   Tidey JW, Pacek LR, Koopmeiners JS, Vandrey R, et al · · 2017 · cited 50× · PMID 27613885 · DOI 10.1093/ntr/ntw199
3. Cumulative vulnerabilities as a potential moderator of response to reduced nicotine content cigarettes.
   Higgins ST, DeSarno M, Bunn JY, Gaalema DE, et al · · 2021 · cited 10× · PMID 34242666 · DOI 10.1016/j.ypmed.2021.106714
4. Relating individual differences in nicotine dependence severity to underpinning motivational and pharmacological processes among smokers from vulnerable populations.
   Higgins ST, DeSarno M, Davis DR, Nighbor T, et al · · 2020 · cited 9× · PMID 32628945 · DOI 10.1016/j.ypmed.2020.106189
5. A behavioral economic perspective on smoking persistence in serious mental illness.
   Tidey JW. · · 2016 · cited 8× · PMID 27196141 · DOI 10.1016/j.ypmed.2016.05.015
6. 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.
   Oliver AC, DeSarno M, Irvin CG, Kaminsky D, et al · · 2022 · cited 6× · PMID 34255068 · DOI 10.1093/ntr/ntab145
7. Potential effects of nicotine content in cigarettes on use of other substances.
   Gaalema DE, Snell LM, Tidey JW, Sigmon SC, et al · · 2022 · cited 4× · PMID 36208817 · DOI 10.1016/j.ypmed.2022.107290