Trial Outcomes & Findings for Low Nicotine Cigarettes, Smoking, and Chronic Pain (NCT NCT05032755)

Last Updated: 2025-08-29

Results Overview

Average number of cigarettes smoked per day over the past week, as reported on timeline follow-back interview at each weekly visit

Recruitment status

COMPLETED

Study phase

Target enrollment

40 participants

Primary outcome timeframe

Weekly for 5 weeks

Results posted on

2025-08-29

Participant Flow

Participants were recruited from Duke University Medical Center and the surrounding area from August, 2023 through May, 2024.

A total of 40 participants were determined to be eligible and enrolled in the study. Of these, 5 withdrew prior to randomization due to scheduling difficulty (n=2), PI decision following repeated no-shows (n=1), inability to abstain from smoking for the baseline abstinent visit (n=1) and loss to contact (n=1).

Participant milestones

Participant milestones
Measure	VLNC Group Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Overall Study STARTED	19	16
Overall Study COMPLETED	19	16
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Low Nicotine Cigarettes, Smoking, and Chronic Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	Total n=35 Participants Total of all reporting groups
Age, Continuous	50.6 years STANDARD_DEVIATION 9.69 • n=39 Participants	49.8 years STANDARD_DEVIATION 8.15 • n=41 Participants	50.3 years STANDARD_DEVIATION 8.9 • n=35 Participants
Sex: Female, Male Female	11 Participants n=39 Participants	11 Participants n=41 Participants	22 Participants n=35 Participants
Sex: Female, Male Male	8 Participants n=39 Participants	5 Participants n=41 Participants	13 Participants n=35 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=39 Participants	1 Participants n=41 Participants	1 Participants n=35 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=39 Participants	15 Participants n=41 Participants	34 Participants n=35 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Asian	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Black or African American	5 Participants n=39 Participants	5 Participants n=41 Participants	10 Participants n=35 Participants
Race (NIH/OMB) White	14 Participants n=39 Participants	11 Participants n=41 Participants	25 Participants n=35 Participants
Race (NIH/OMB) More than one race	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Region of Enrollment United States	19 participants n=39 Participants	16 participants n=41 Participants	35 participants n=35 Participants

PRIMARY outcome

Timeframe: Weekly for 5 weeks

Average number of cigarettes smoked per day over the past week, as reported on timeline follow-back interview at each weekly visit

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Cigarettes Smoked Per Day Week 1	14.5 cigarettes/day Standard Deviation 5.54	17.2 cigarettes/day Standard Deviation 7.39
Cigarettes Smoked Per Day Week 2	16.4 cigarettes/day Standard Deviation 8.99	20.3 cigarettes/day Standard Deviation 6.49
Cigarettes Smoked Per Day Week 3	13.5 cigarettes/day Standard Deviation 7.15	23.4 cigarettes/day Standard Deviation 5.86
Cigarettes Smoked Per Day Week 4	13.8 cigarettes/day Standard Deviation 7.84	22.5 cigarettes/day Standard Deviation 5.87
Cigarettes Smoked Per Day Week 5	14.0 cigarettes/day Standard Deviation 8.95	23.8 cigarettes/day Standard Deviation 8.09

PRIMARY outcome

Timeframe: Weekly for 5 weeks

The FTCD is a widely used 6-item measure of dependence, with total scores ranging from 0 (low dependence) to 10 (high dependence)

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Weekly Measures of Cigarette Dependence as Assessed by the Fagerstrom Test of Cigarette Dependence (FTCD) Week 1	4.95 score on a scale Standard Deviation 2.12	5.56 score on a scale Standard Deviation 1.59
Weekly Measures of Cigarette Dependence as Assessed by the Fagerstrom Test of Cigarette Dependence (FTCD) Week 2	4.32 score on a scale Standard Deviation 2.31	5.88 score on a scale Standard Deviation 1.78
Weekly Measures of Cigarette Dependence as Assessed by the Fagerstrom Test of Cigarette Dependence (FTCD) Week 3	4.11 score on a scale Standard Deviation 2.35	6.19 score on a scale Standard Deviation 1.56
Weekly Measures of Cigarette Dependence as Assessed by the Fagerstrom Test of Cigarette Dependence (FTCD) Week 4	3.84 score on a scale Standard Deviation 2.34	6.12 score on a scale Standard Deviation 1.67
Weekly Measures of Cigarette Dependence as Assessed by the Fagerstrom Test of Cigarette Dependence (FTCD) Week 5	4.16 score on a scale Standard Deviation 2.34	6.25 score on a scale Standard Deviation 1.73

PRIMARY outcome

Timeframe: Weekly for 5 visits

The MNWS is a 7-item measure of withdrawal symptoms, with responses indicated on a likert scale ranging from 0 (none) to 4 (severe). The total score ranges from 0 to 28, with higher scores indicating greater withdrawal symptoms.

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Weekly Ratings of Withdrawal Symptoms as Measured by the Minnesota Tobacco Withdrawal Scale Week 1	12.05 score on a scale Standard Deviation 5.64	10.69 score on a scale Standard Deviation 4.25
Weekly Ratings of Withdrawal Symptoms as Measured by the Minnesota Tobacco Withdrawal Scale Week 2	12.42 score on a scale Standard Deviation 6.31	10.38 score on a scale Standard Deviation 4.72
Weekly Ratings of Withdrawal Symptoms as Measured by the Minnesota Tobacco Withdrawal Scale Week 3	12.32 score on a scale Standard Deviation 6.25	12.38 score on a scale Standard Deviation 3.95
Weekly Ratings of Withdrawal Symptoms as Measured by the Minnesota Tobacco Withdrawal Scale Week 4	9.84 score on a scale Standard Deviation 6.27	11.25 score on a scale Standard Deviation 5.53
Weekly Ratings of Withdrawal Symptoms as Measured by the Minnesota Tobacco Withdrawal Scale Week 5	10.42 score on a scale Standard Deviation 5.64	10.69 score on a scale Standard Deviation 3.44

PRIMARY outcome

Timeframe: Weekly for 5 visits

The BPI is a well-validated 11-item self-report measure. Pain intensity is calculated as the average of 3 items (worst pain, least pain, and average pain). Scores are averaged with the total score ranging from 0 to 10 with higher scores indicating more pain.

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Weekly Changes in Pain Intensity as Measured by the Past-week Version of the Brief Pain Inventory (BPI) Week 1	5.1 score on a scale Standard Deviation 1.89	4.04 score on a scale Standard Deviation 1.02
Weekly Changes in Pain Intensity as Measured by the Past-week Version of the Brief Pain Inventory (BPI) Week 2	4.97 score on a scale Standard Deviation 1.8	3.88 score on a scale Standard Deviation 1.12
Weekly Changes in Pain Intensity as Measured by the Past-week Version of the Brief Pain Inventory (BPI) Week 3	4.61 score on a scale Standard Deviation 2.4	4.23 score on a scale Standard Deviation 1.85
Weekly Changes in Pain Intensity as Measured by the Past-week Version of the Brief Pain Inventory (BPI) Week 4	4.05 score on a scale Standard Deviation 2.3	3.98 score on a scale Standard Deviation 2.17
Weekly Changes in Pain Intensity as Measured by the Past-week Version of the Brief Pain Inventory (BPI) Week 5	3.84 score on a scale Standard Deviation 1.95	4.29 score on a scale Standard Deviation 1.99

PRIMARY outcome

Timeframe: Baseline (pre-intervention) abstinence session (i.e., prior to week 1), follow-up abstinence session (immediately after final week of cigarette use; i.e., week 5)

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Ratings of Withdrawal Symptoms During Smoking Abstinence, as Measured by the Minnesota Tobacco Withdrawal Scale (MNWS) Week 1 (pre-intervention) abstinence session	13.2 score on a scale Standard Deviation 5.8	14.4 score on a scale Standard Deviation 4.56
Ratings of Withdrawal Symptoms During Smoking Abstinence, as Measured by the Minnesota Tobacco Withdrawal Scale (MNWS) Week 5 (post-intervention) abstinence session	8.63 score on a scale Standard Deviation 5.93	11.6 score on a scale Standard Deviation 4.66

PRIMARY outcome

Timeframe: Baseline (pre-intervention) abstinence session (i.e., before week 1), follow-up abstinence session (immediately after final week of cigarette use; i.e., week 5)

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Pain Intensity During Smoking Abstinence as Measured by the Past 24-hour Version of the Brief Pain Inventory (BPI) Week 1 (pre-intervention) abstinence session	4.53 score on a scale Standard Deviation 2.06	3.83 score on a scale Standard Deviation 1.78
Pain Intensity During Smoking Abstinence as Measured by the Past 24-hour Version of the Brief Pain Inventory (BPI) Week 5 (post-intervention) abstinence session	3.51 score on a scale Standard Deviation 2.26	2.85 score on a scale Standard Deviation 1.64

OTHER_PRE_SPECIFIED outcome

Timeframe: Weekly visits 1, 3, and 5

The PSI is a 9-item measure of pain as a motivator to smoke, smoking to cope with pain, and pain as a barrier to smoking cessation, with responses indicated on a 7-point likert scale ranging from 0 (not true at all) to 6 (extremely true). Scores are averaged and the total score ranges from 0-6, with higher scores indicating that pain is a greater motivator to smoke.

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Changes in Smoking to Cope With Pain as Measured by the Pain and Smoking Inventory (PSI) Week 1	2.87 score on a scale Standard Deviation 1.79	2.29 score on a scale Standard Deviation 1.16
Changes in Smoking to Cope With Pain as Measured by the Pain and Smoking Inventory (PSI) Week 3	2.61 score on a scale Standard Deviation 1.77	2.52 score on a scale Standard Deviation 1.46
Changes in Smoking to Cope With Pain as Measured by the Pain and Smoking Inventory (PSI) Week 5	2.13 score on a scale Standard Deviation 1.86	2.44 score on a scale Standard Deviation 1.33

OTHER_PRE_SPECIFIED outcome

Timeframe: Weekly visits 1, 3, and 5

The contemplation ladder is a single-item measure of a person's current thoughts about quitting smoking, ranging from 0 (I have no thought of quitting) to 10 (I am doing something to try to quit)

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Changes in Motivation to Quit Smoking as Measured by the Contemplation Ladder Week 1	5 score on a scale Standard Deviation 3.06	3.88 score on a scale Standard Deviation 2.55
Changes in Motivation to Quit Smoking as Measured by the Contemplation Ladder Week 3	5.26 score on a scale Standard Deviation 2.75	5.31 score on a scale Standard Deviation 2.57
Changes in Motivation to Quit Smoking as Measured by the Contemplation Ladder Week 5	5.95 score on a scale Standard Deviation 3.06	5.63 score on a scale Standard Deviation 3.18

OTHER_PRE_SPECIFIED outcome

Timeframe: Weekly visits 1, 3, and 5

The SEQ-12 is a 12-item measure yielding scores for self-efficacy when faced with both external (situational) or internal (e.g., affective) stimuli. Responses on each item range from 1 to 5, with higher scores indicating greater confidence in abstaining from smoking. Total score ranges from 12 to 60.

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Changes in Smoking Abstinence Self-efficacy as Measured by the Smoking Self-Efficacy Questionnaire (SEQ-12) Week 1	24.11 score on a scale Standard Deviation 6.88	27.44 score on a scale Standard Deviation 11.12
Changes in Smoking Abstinence Self-efficacy as Measured by the Smoking Self-Efficacy Questionnaire (SEQ-12) Week 3	29.68 score on a scale Standard Deviation 11.72	31 score on a scale Standard Deviation 8.92
Changes in Smoking Abstinence Self-efficacy as Measured by the Smoking Self-Efficacy Questionnaire (SEQ-12) Week 5	27.21 score on a scale Standard Deviation 8.64	25.63 score on a scale Standard Deviation 6.51

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (pre-randomization; i.e., week 1) and the first and last weeks of study cigarette use (i.e., weeks 2 and 5)

Responses to the question "Right now, how intense is your pain?", rated on a 1 (not at all) to 9 (extremely) likert scale at multiple timepoints throughout the day over the course of a week. All responses recorded within a week (up to 35 per participant) were averaged to create a single value ranging from 1 to 9, with higher scores indicating more pain.

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Pain Intensity Ratings During Ecological Momentary Assessment Week 1 (Baseline)	4.40 units on a scale Standard Deviation 1.88	3.23 units on a scale Standard Deviation 1.54
Pain Intensity Ratings During Ecological Momentary Assessment Week 2	4.23 units on a scale Standard Deviation 2.06	3.09 units on a scale Standard Deviation 1.55
Pain Intensity Ratings During Ecological Momentary Assessment Week 5	3.67 units on a scale Standard Deviation 2.10	3.05 units on a scale Standard Deviation 1.57

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (pre-randomization; i.e., week 1) and the first and last weeks of study cigarette use (i.e., weeks 2 and 5)

Responses to question "How strong is your current urge to smoke?", rated on a 1 (not strong at all) to 9 (extremely strong) likert scale, assessed at multiple timepoints each day. All responses recorded within a week (up to 35 per participant) were averaged to create a single value ranging from 1 to 9, with higher scores indicating greater smoking urge.

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Smoking Urge Ratings During Ecological Momentary Assessment Week 1 (Baseline)	4.74 units on a scale Standard Deviation 2.47	3.78 units on a scale Standard Deviation 2.26
Smoking Urge Ratings During Ecological Momentary Assessment Week 2	4.43 units on a scale Standard Deviation 2.32	3.40 units on a scale Standard Deviation 2.09
Smoking Urge Ratings During Ecological Momentary Assessment Week 5	3.23 units on a scale Standard Deviation 2.33	3.98 units on a scale Standard Deviation 2.39

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (pre-randomization; i.e., week 1), and the first and last weeks of study cigarette use (i.e., weeks 2 and 5)

Average of responses to 4 negative affect items (anxious, irritable, guilty sad) using the question prompt, "Right now, how much are you feeling...?", rated on a 1 (not at all) to 9 (extremely) likert scale, assessed at multiple times per day. All responses recorded within a week (up to 35 per participant) were averaged to create a single value ranging from 1 to 9, with higher scores indicating greater negative affect.

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Negative Affect Ratings During Ecological Momentary Assessment Week 5	2.43 units on a scale Standard Deviation 1.60	2.05 units on a scale Standard Deviation 1.03
Negative Affect Ratings During Ecological Momentary Assessment Week 1 (Baseline)	2.44 units on a scale Standard Deviation 1.21	1.89 units on a scale Standard Deviation 0.91
Negative Affect Ratings During Ecological Momentary Assessment Week 2	2.98 units on a scale Standard Deviation 1.61	1.91 units on a scale Standard Deviation 1.13

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (pre-randomization; i.e., week 1) and the first and last weeks of study cigarette use (i.e., weeks 2 and 5)

Proportion of "yes" responses to question "Are you about to smoke a cigarette right now?", assessed multiple times during the day. Total "yes" responses were divided by total observations within each week to calculate proportion of responses.

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Intent to Smoke During Ecological Momentary Assessment Week 1 (Baseline)	0.35 proportion of responses Standard Deviation 0.48	0.26 proportion of responses Standard Deviation 0.44
Intent to Smoke During Ecological Momentary Assessment Week 2	0.38 proportion of responses Standard Deviation 0.49	0.30 proportion of responses Standard Deviation 0.46
Intent to Smoke During Ecological Momentary Assessment Week 5	0.21 proportion of responses Standard Deviation 0.41	0.32 proportion of responses Standard Deviation 0.47

POST_HOC outcome

Timeframe: Baseline (pre-intervention) abstinence session (i.e., before week 1), follow-up abstinence session (immediately after final week of cigarette use; i.e., week 5)

The QSU-Brief is a 5-item measure of urge to smoke, with responses indicated on a 7-point likert scale ranging from 0 (strongly disagree) to 7 (strongly agree). Total scores range from 0 to 35, with higher scores indicating greater craving.

Outcome measures

Outcome measures
Measure	VLNC Group n=19 Participants Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 Participants Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Changes in Abstinence-induced Craving as Measured by the Questionnaire of Smoking Urges-Brief (QSU-Brief) Week 1 (pre-intervention) abstinence session	26.3 score on a scale Standard Deviation 5.75	26.7 score on a scale Standard Deviation 6.34
Changes in Abstinence-induced Craving as Measured by the Questionnaire of Smoking Urges-Brief (QSU-Brief) Week 5 (post-intervention) abstinence session	16.7 score on a scale Standard Deviation 9.42	21.8 score on a scale Standard Deviation 7.57

Adverse Events

VLNC Group

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

NNC Group

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Maggie Sweitzer

Duke University Medical Center

Phone: 919-668-0094

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	VLNC Group n=19 participants at risk Participants in this condition will be provided with Spectrum NRC102/103 (nonmenthol/menthol) cigarettes, which have a nicotine content of approximately 0.4 mg/g tobacco with reported nicotine yield (ISO) of 0.03 +/- 0.01 mg and a tar yield of 9 +/- 1.5. Participants will be asked to smoke only study cigarettes for 4 weeks. SPECTRUM NRC 102/103 investigational cigarettes: Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	NNC Group n=16 participants at risk Participants in this condition will be provided with Spectrum NRC600/601 (non-menthol/menthol) cigarettes, which have a nicotine content of approximately 15.8 mg/g tobacco with reported nicotine yield (ISO) of 0.8 +/- 0.15 mg and a tar yield of 10.5 +/- 1.5. SPECTRUM NRC 600/601 investigational cigarettes: Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
Psychiatric disorders depressive symptoms	5.3% 1/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	0.00% 0/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Surgical and medical procedures dental extraction	5.3% 1/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	0.00% 0/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Gastrointestinal disorders nausea and dizziness	0.00% 0/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	12.5% 2/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Product Issues 100% increase in cigarettes/day	0.00% 0/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	6.2% 1/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Vascular disorders Elevated blood pressure	15.8% 3/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	18.8% 3/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Injury, poisoning and procedural complications Fall, hurt ribs	0.00% 0/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	6.2% 1/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Nervous system disorders dizziness and blurred vision	0.00% 0/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	6.2% 1/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Nervous system disorders pinched nerve in hand	5.3% 1/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	0.00% 0/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Gastrointestinal disorders heartburn	5.3% 1/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	0.00% 0/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Cardiac disorders irregular heartrate	5.3% 1/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	0.00% 0/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Nervous system disorders tingling in chest	5.3% 1/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	0.00% 0/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Musculoskeletal and connective tissue disorders knee, joint, or shoulder pain	0.00% 0/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	31.2% 5/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Musculoskeletal and connective tissue disorders mild pain in sternum	0.00% 0/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	6.2% 1/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Respiratory, thoracic and mediastinal disorders sinus irritation	5.3% 1/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	0.00% 0/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Infections and infestations viral infection	5.3% 1/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	0.00% 0/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Social circumstances increased stress	10.5% 2/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	6.2% 1/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Psychiatric disorders increased anxiety	10.5% 2/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	18.8% 3/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Psychiatric disorders increased irritability	5.3% 1/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	0.00% 0/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Musculoskeletal and connective tissue disorders increased back pain	26.3% 5/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	37.5% 6/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Endocrine disorders thyroid flare-up	0.00% 0/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	6.2% 1/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Infections and infestations abcess	5.3% 1/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	6.2% 1/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Gastrointestinal disorders blocked salivary duct	0.00% 0/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	6.2% 1/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Social circumstances Grief/sadness	0.00% 0/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	12.5% 2/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Nervous system disorders narcolepsy diagnosis	5.3% 1/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	0.00% 0/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Respiratory, thoracic and mediastinal disorders sore throat	0.00% 0/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	6.2% 1/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Injury, poisoning and procedural complications minor back injury	5.3% 1/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	0.00% 0/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)
Hepatobiliary disorders cirrhosis diagnosis	0.00% 0/19 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)	6.2% 1/16 • 5 weeks including 1 week pre-randomization (abstinence 1 to weekly visit 1) and 4 weeks of study cigarette use (weekly visit 1 abstinence 2)