Chronic PainVLNCPainNCT05032755

Low Nicotine Cigarettes, Smoking, and Chronic Pain

A study testing SPECTRUM NRC 102/103 investigational cigarettes and SPECTRUM NRC 600/601 investigational cigarettes in people with Chronic Pain and Smoking, Cigarette, run by Duke University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to evaluate the effects of switching to very low nicotine content (VLNC) cigarettes versus normal nicotine content (NNC) cigarettes on experiences with craving, withdrawal, and pain among individuals with chronic back pain who smoke cigarettes daily. Read more about this study

Who is it for?: Ages 21 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Chronic Pain, Smoking, Cigarette
What is being tested?: SPECTRUM NRC 102/103 investigational cigarettes and SPECTRUM NRC 600/601 investigational cigarettes
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: 1 siteUnited States
Study dates: 23 Jun 2022to 4 Jul 2024
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

diagnosis of non-cancer chronic (>3 months) back pain (confirmed in medical record or by current provider);
Pain duration of >=3 months with an average intensity of >/= 4/10 or worst pain >/=6/10 as assessed by Graded Chronic Pain Scale (GCPS);
smoking at least 10 cigarettes per day for > 2 years;
expired breath CO concentration > 10 ppm;
have an iPhone or Android smartphone capable of running EMA software

Who cannot join

actively taking steps to quit smoking;
inability to attend all required experimental sessions;
report of significant health problems;
systolic blood pressure > 160 or diastolic blood pressure > 100;
resting heart rate > 100;
breath alcohol level > 0.0;

Show all 19Show fewer

current use of opioid pain relievers;
lifetime history of bipolar or psychotic disorder;
current unstable psychiatric disorder as assessed by the MINI;
use of non-cigarette tobacco products > 8 times in the past 30 days;
current use of nicotine replacement therapy (NRT) or other smoking cessation strategy;
use of Spectrum investigational cigarettes in the past year;
quit attempt in the past 30 days resulting in > 3 days abstinence;
past year alcohol or substance use disorder;
use of illegal drugs as measured by urine drug screen;
pain complaint due to specific medical conditions (e.g., cancer, rheumatoid arthritis, complex regional pain syndrome);
spine surgery within the past year or planned surgery within the timeframe of the study;
current disability litigation pending;
positive pregnancy test among women

Trial locations and contacts

1 site in 1 country.

United States1 site

Duke University Medical Center
Durham, North Carolina, 27705

Other trials in United States

About this study

Official title: Using Very Low Nicotine Cigarettes to Disrupt the Pain-smoking Reinforcement Cycle

Read the detailed description

The goal of this study is to evaluate the effects of very low nicotine content (VLNC) cigarettes on the dynamic associations between smoking, pain, and withdrawal among daily smokers with chronic (> 3 months) non-cancer back pain (n=48). Participants will complete an initial screening session to determine eligibility, followed by a baseline abstinence session in which measures of pain and withdrawal will be assessed following 24 hrs abstinence from smoking. At the conclusion of this session participants will receive training in ecological momentary assessment (EMA) procedures and software will be installed on their smartphone. Participants will then complete a 1-week baseline period, in which they will complete EMA while continuing to smoke usual brand cigarettes. During EMA, participants will receive 6 randomly spaced daily prompts, with 15 questions to complete about smoking behavior, mood, and current pain. In addition, participants will be asked to use their smartphone to indicate whenever they are about to smoke a cigarette. Three of these cigarettes each day will be randomly selected for assessment: in these cases participants will be asked to respond to the same 15 question before and after smoking the cigarette. Participants will also complete end of day questionnaires.

After the 1 week baseline period, participants will be randomly assigned to four weeks of either VLNCs (n=24) or normal nicotine content (NNC) cigarettes (n=24). During this period, participants will be asked to smoke only study cigarettes. Participants will attend weekly laboratory visits to provide biochemical verification of cigarette adherence (urine samples) and complete questionnaires. Study cigarettes will also be provided and collected at these visits. Two of the four weekly urine samples will be selected for analysis. Participants will also complete EMA during weeks 1 and 4 of study cigarette use. End of day questionnaires will continue throughout the 4 weeks.

At the conclusion of the study, participants will attend a final laboratory visit after abstaining from smoking for 24 hours. During this session, self-report measures of pain, craving, and withdrawal will be assessed, along with biochemical verification (breath sample) of abstinence.

Conditions: Chronic Pain, Smoking, Cigarette
Being tested: SPECTRUM NRC 102/103 investigational cigarettes, SPECTRUM NRC 600/601 investigational cigarettes
Medical subject headings: Chronic Pain, Cigarette Smoking

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SPECTRUM NRC 102/103 investigational cigarettesOther
Very low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes
SPECTRUM NRC 600/601 investigational cigarettesOther
Normal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes

Study groups in NCT05032755
Study group	Role	What they receive
VLNC Group	Experimental	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. Receives: Other: SPECTRUM NRC 102/103 investigational cigarettes
NNC Group	Active comparator	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. Receives: Other: SPECTRUM NRC 600/601 investigational cigarettes

What is being measured

The primary outcome is the main question the study is designed to answer.

Cigarettes Smoked Per Day
Average number of cigarettes smoked per day over the past week, as reported on timeline follow-back interview at each weekly visit
Measured: Weekly for 5 weeks
Weekly Measures of Cigarette Dependence as Assessed by the Fagerstrom Test of Cigarette Dependence (FTCD)
The FTCD is a widely used 6-item measure of dependence, with total scores ranging from 0 (low dependence) to 10 (high dependence)
Measured: Weekly for 5 weeks
Weekly Ratings of Withdrawal Symptoms as Measured by the Minnesota Tobacco Withdrawal Scale
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.
Measured: Weekly for 5 visits
Weekly Changes in Pain Intensity as Measured by the Past-week Version of the Brief Pain Inventory (BPI)
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.
Measured: Weekly for 5 visits
Ratings of Withdrawal Symptoms During Smoking Abstinence, as Measured by the Minnesota Tobacco Withdrawal Scale (MNWS)
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.
Measured: 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)
Pain Intensity During Smoking Abstinence as Measured by the Past 24-hour Version of the Brief Pain Inventory (BPI)
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.
Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Jun 20224 Jul 2024

First posted2 Sep 2021
Study start23 Jun 2022
Primary completion4 Jul 2024
Study completion4 Jul 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Chronic PainStudies of the same condition, open and under way.
More trials run by Duke UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05032755
Sponsor's protocol ID: Pro00108705
Other IDs: R21DA052729
Acronym: VLNCPain
Status last verified: Jun 2025
First submitted: 27 Aug 2021
Last updated: 29 Aug 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Rubenstein D, Green MJ, Keefe FJ, McClernon FJ, Sweitzer MM. Ecological momentary assessment of cigarette smoking behavior and pain intensity among individuals with chronic back pain who smoke. J Pain. 2025 Mar;28:104776. doi: 10.1016/j.jpain.2025.104776. Epub 2025 Jan 5.
PubMed 39765280

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 29 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Using Very Low Nicotine Cigarettes to Disrupt the Pain-smoking Reinforcement Cycle
ClinicalTrials.gov ID: NCT05032755
Acronym / sponsor ID: VLNCPain / Pro00108705
Conditions: Chronic Pain, Smoking, Cigarette
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: Duke UniversityUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: 23 Jun 2022 (actual)
Primary completion: 4 Jul 2024 (actual)
Study completion: 4 Jul 2024 (actual)
First posted: 2 Sep 2021 (actual)
Results: Posted 13 Aug 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
VLNC Group	Experimental	Other: SPECTRUM NRC 102/103 investigational cigarettesParticipants 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.
NNC Group	Active comparator	Other: SPECTRUM NRC 600/601 investigational cigarettesParticipants 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.

Who may qualify

Ages: 21 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

diagnosis of non-cancer chronic (>3 months) back pain (confirmed in medical record or by current provider);
Pain duration of >=3 months with an average intensity of >/= 4/10 or worst pain >/=6/10 as assessed by Graded Chronic Pain Scale (GCPS);
smoking at least 10 cigarettes per day for > 2 years;
expired breath CO concentration > 10 ppm;
have an iPhone or Android smartphone capable of running EMA software

Key exclusion criteria (19 listed)

actively taking steps to quit smoking;
inability to attend all required experimental sessions;
report of significant health problems;
systolic blood pressure > 160 or diastolic blood pressure > 100;
resting heart rate > 100;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SPECTRUM NRC 102/103 investigational cigarettesVery low nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	Other	VLNC Group
SPECTRUM NRC 600/601 investigational cigarettesNormal nicotine content (nonmenthol/menthol) SPECTRUM investigational cigarettes	Other	NNC Group

Primary outcome

Cigarettes Smoked Per Day
Time frame: 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
Weekly Measures of Cigarette Dependence as Assessed by the Fagerstrom Test of Cigarette Dependence (FTCD)
Time frame: 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)
Weekly Ratings of Withdrawal Symptoms as Measured by the Minnesota Tobacco Withdrawal Scale
Time frame: 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.
Weekly Changes in Pain Intensity as Measured by the Past-week Version of the Brief Pain Inventory (BPI)
Time frame: 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.
Ratings of Withdrawal Symptoms During Smoking Abstinence, as Measured by the Minnesota Tobacco Withdrawal Scale (MNWS)
Time frame: 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)
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.
Pain Intensity During Smoking Abstinence as Measured by the Past 24-hour Version of the Brief Pain Inventory (BPI)
Time frame: 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 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.

Results and safety

Results posted to the registry on 13 Aug 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
VLNC Group	19	19
NNC Group	16	16

Primary outcome: Cigarettes Smoked Per Day

Time frame: Weekly for 5 weeks. Mean (Standard Deviation). Unit: cigarettes/day

Measure	VLNC Group n = 19	NNC Group n = 16
Week 1	14.5 (5.54)	17.2 (7.39)
Week 2	16.4 (8.99)	20.3 (6.49)
Week 3	13.5 (7.15)	23.4 (5.86)
Week 4	13.8 (7.84)	22.5 (5.87)
Week 5	14.0 (8.95)	23.8 (8.09)

VLNC Group vs NNC Group: beta estimate: 1.902, p <.0001, Mixed Models Analysis

Primary outcome: Weekly Measures of Cigarette Dependence as Assessed by the Fagerstrom Test of Cigarette Dependence (FTCD)

Time frame: Weekly for 5 weeks. Mean (Standard Deviation). Unit: score on a scale

Measure	VLNC Group n = 19	NNC Group n = 16
Week 1	4.95 (2.12)	5.56 (1.59)
Week 2	4.32 (2.31)	5.88 (1.78)
Week 3	4.11 (2.35)	6.19 (1.56)
Week 4	3.84 (2.34)	6.12 (1.67)
Week 5	4.16 (2.34)	6.25 (1.73)

VLNC Group vs NNC Group: beta estimate: 0.368, p <.0001, Mixed Models Analysis

Primary outcome: Weekly Ratings of Withdrawal Symptoms as Measured by the Minnesota Tobacco Withdrawal Scale

Time frame: Weekly for 5 visits. Mean (Standard Deviation). Unit: score on a scale

Measure	VLNC Group n = 19	NNC Group n = 16
Week 1	12.05 (5.64)	10.69 (4.25)
Week 2	12.42 (6.31)	10.38 (4.72)
Week 3	12.32 (6.25)	12.38 (3.95)
Week 4	9.84 (6.27)	11.25 (5.53)
Week 5	10.42 (5.64)	10.69 (3.44)

VLNC Group vs NNC Group: beta estimate: 0.672, p = 0.065, Mixed Models Analysis

Primary outcome: Weekly Changes in Pain Intensity as Measured by the Past-week Version of the Brief Pain Inventory (BPI)

Time frame: Weekly for 5 visits. Mean (Standard Deviation). Unit: score on a scale

Measure	VLNC Group n = 19	NNC Group n = 16
Week 1	5.1 (1.89)	4.04 (1.02)
Week 2	4.97 (1.8)	3.88 (1.12)
Week 3	4.61 (2.4)	4.23 (1.85)
Week 4	4.05 (2.3)	3.98 (2.17)
Week 5	3.84 (1.95)	4.29 (1.99)

VLNC Group vs NNC Group: beta estimate: 0.364, p = 0.007, Mixed Models Analysis

Adverse events

Time frame: 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). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
VLNC Group	0 of 19 (0%)	12 of 19 (63.2%)	0 of 19
NNC Group	0 of 16 (0%)	13 of 16 (81.3%)	0 of 16

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39765280Rubenstein D, Green MJ, Keefe FJ, McClernon FJ, Sweitzer MM. Ecological momentary assessment of cigarette smoking behavior and pain intensity among individuals with chronic back pain who smoke. J Pain. 2025 Mar;28:104776. doi: 10.1016/j.jpain.2025.104776. Epub 2025 Jan 5.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Maggie Sweitzer principal investigator

Duke University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cigarettes Smoked Per Day (time frame: Weekly for 5 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05032755, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2025; AzTrials last refreshed its copy on 6 Nov 2026.