Using Pod Based e-Cigarettes and Nicotine Pouches to Reduce Harm for Adults With Low Socioeconomic Status Who Smoke: A Pilot Randomized Controlled Trial

Abstract

Introduction

Alternative Nicotine Delivery Systems (ANDS) such as e-cigarettes (EC) and oral nicotine pouches (ONP) may facilitate the substitution of smoking for those unwilling to quit. This pilot study assesses the harm-reduction potential of EC and ONP among smokers with low socioeconomic status (SES).

Aims and Methods

Adults who smoked daily in the past 6 months, had a household income < 250% federal poverty level and had no intention of quitting smoking in the next 30 days were randomized 2:2:1 to 8 weeks of 5% nicotine EC; 4 mg ONP or assessment-only control (CC). The primary outcome was a within-group change in cigarettes per day (CPD) from Baseline to week 8.

Results

Forty-five individuals were randomized (EC: N = 18; ONP: N = 18; CC: N = 9). Analyses included 33 participants who completed the week 8 visit. The mean age was 50.1 years (SD: 10.7) and the average CPD at baseline was 13.9 (SD: 10.1). For those randomized to EC, the average CPD decreased from 14.7 (95% CI: 10.3 to 19.1) at the Baseline to 2.9 (95% CI: .1 to 5.8) at week 8 (p-value < .001). For those randomized to ONP, average CPD decreased from 15.0 (95% CI: 5.0 to 24.9) to 8.3 (95% CI: 1.3 to 15.2) by week 8 (p-value = .01). In the EC and ONP groups, respectively, 4 (28.6%) and 1 (8.3%) participant fully switched from smoking to the ANDS product by week 8.

Conclusions

Individuals with low SES who smoke had lower CPD after switching to EC or ONP. These findings show the potential of ANDS in helping smokers switch to less harmful devices.

Implications

This study provides novel evidence that e-cigarettes and nicotine pouches can be a harm-reduction tool for individuals with lower SES who smoke and are not willing to quit smoking, contributing to reducing tobacco-related disparities in this population.

Clinical Trials Identifier: NCT05327439

Introduction

Individuals with lower socioeconomic status (SES) who smoke are one of the groups who continue to experience tobacco-related disparities in the United States. They have an increased risk of smoking, are less likely to quit, and have the greatest burden of tobacco-related diseases in the United States.^1,2 In 2021, the prevalence of cigarette use in the past month for adults 18 years and older with a low-income level (income-to-poverty ratio lower than 1.99) was 20.6% in the U.S., compared to 14.5% for the adult population in the U.S.² SES is a multifactorial measure; thus, individuals who have more than one level of SES disadvantage often have an even higher smoking prevalence. For example, the prevalence of smoking in 2017 was 40% for adults 25 years and older in the U.S. with less than a high school education or GED who also had income below the federal poverty level (FPL). However, it was near 25% for those with income below the FPL who had a high school degree or more.³ The FPL is a measure issued by the US Department of Health and Human Services to define income cutpoints to receive government programs and benefits.⁴

Tobacco-related inequities among individuals with lower SES are exacerbated by low cessation rates.^5,6 Adults 18 and older who smoke in the United States and have an income below the FPL have lower quit ratios compared to those at or above the poverty level (42.2% and 64.5% in 2017, respectively).³ They are also less likely to make quit attempts, receive advice from health professionals regarding quitting, or use pharmacotherapy to quit.⁷ Barriers to quitting smoking among people with low SES include poor access to healthcare, discrimination, and individual stressors such as financial instability, stigma, and lack of social support.^5,8 In addition, evidence-based smoking cessation interventions such as nicotine replacement therapy (NRT) have been historically less effective for individuals with lower SES.^5,9–11 This evidence suggests that alternative strategies should be pursued to promote tobacco harm reduction for individuals with low SES who smoke combustible cigarettes (CC) and are unable or unwilling to quit smoking.

Alternative nicotine delivery systems (ANDS) offer a promising avenue for reducing cigarette use within this population. One of the most popular ANDS is electronic cigarettes (EC), which are battery-powered devices that create nicotine-containing aerosol with fewer lung irritants and carcinogens than combustible tobacco.¹² Though the use of EC is not without harm, there is growing and consistent evidence that the exposure to toxic substances from CC is dramatically higher than in EC, and that those who switch from CC to EC smoke fewer cigarettes per day, have lower carbon monoxide (CO) levels, and lower biomarkers of tobacco exposure and harm.^13–17 In addition, a comprehensive Cochrane review of randomized controlled trials (RCTs) including both adult smokers motivated and unmotivated to quit, showed that adults using EC are more likely to achieve 6-month cessation from cigarettes than those who received either behavioral support only, no support for cessation, placebo EC,¹⁸ and even those using nicotine replacement therapy.^18,19 Although harm-reduction effects of EC for individuals who use both EC and CC are understudied,¹⁶ there is growing evidence from RCTs that even partial CC substitution with EC can have harm-reduction benefits.^17,20 It is important to underscore that EC is not approved by the US Food and Drug Administration (FDA) as a smoking cessation product, but EC is approved as a smoking cessation method in other countries such as the UK.^21,22

Although EC could be a harm-reduction alternative for people with low SES who smoke, adults in England with lower SES (defined as a social grade based on occupation) had lower overall odds of EC use compared to those with high SES (N = 16 232).²³ Individuals 18 years and older with income < 100% of the FPL or with income <$10 000 in the Population Assessment of Tobacco and Health (PATH) study were also less likely to successfully switch from exclusive CC use to exclusive EC use^24,25 and more likely to believe that EC is more harmful than CC than those with higher income.²⁵ These findings could further widen tobacco-related disparities. Encouraging switching from CC to EC could be effective in reducing disparities in smoking-related morbidity and mortality and facilitate smoking cessation for low SES individuals who are not willing or unable to quit smoking.

Nicotine pouches are another ANDS product with the potential to reduce tobacco harm but they are understudied. Nicotine pouches are small disposable pouches containing varying amounts of pharmaceutical-grade nicotine that are placed between the lip and gum.²⁶ Nicotine pouches are a smokeless product that does not contain tobacco leaf, unlike traditional smokeless tobacco or Swedish snus. While tobacco-free oral nicotine pouches are relatively new to the market, 16.4% of a sample of adults 21 years and older in the United States (N = 1583) who use tobacco have tried nicotine pouches and 3% currently use nicotine pouches with another tobacco product.²⁷

In vitro analyses of nicotine pouches showed lower biological activity compared to both tobacco-containing alternatives such as snus and combustible cigarettes.^28–30 Daily toxicant exposure and chemical composition analysis also showed that nicotine pouches contained significantly fewer harmful tobacco constituents compared to snus.^31,32 In fact, nicotine pouches possessed a similar composition profile to medically approved NRT products such as lozenges and nicotine gum.^31,32 Modern nicotine pouches also have nicotine blood plasma level delivery comparable to cigarettes³³ or snus²⁶ and pose a lower potential of abuse compared to cigarettes.^34–36 Such early evidence suggests the potential of incorporating nicotine pouches into tobacco harm-reduction strategies for individuals who are not willing or unable to quit smoking. Most of the evidence on nicotine pouches that is currently available and cited comes from the tobacco industry and, to our knowledge, this is the first study to independently assess the tobacco harm-reduction potential of nicotine pouches.

The objective of this pilot study was to assess the harm-reduction potential of both EC and nicotine pouches among low SES adults who smoke. We conducted a pilot RCT to test the effects of 8 weeks of EC or nicotine pouch use on CC use, cigarette dependence, and complete CC substitution among low SES adults who smoke (3 arms, 2:2:1 randomization). We hypothesized that participants receiving EC or nicotine pouches would smoke fewer CC per day and demonstrate reduced cigarette dependence relative to Baseline (within-subjects change).

Materials and Methods

Study Design

This study is an open-label pilot randomized controlled trial (RCT) testing the harm-reduction potential of e-cigarettes (EC) and nicotine pouches for low SES adults who smoke and are not interested in quitting. The intervention included an 8-week supply of EC, nicotine pouches, or assessment-only control (CC). Participants were randomized to these groups in a 2:2:1 fashion and were followed for 8 weeks. Participants completed a Baseline assessment at week 0, in-person visits at weeks 4 and 8, and follow-up phone calls between the in-person visits at weeks 1, 3, 5, and 7. At the week 8 assessment, participants completed a qualitative exit interview assessing protocol feasibility, acceptability, and barriers to use ANDS. Participants completed a final follow-up call at week 16 to assess ANDS product use after the intervention ended, but the results are not reported here. This study was approved by the Institutional Review Board at Brown University.

Participants

Participants were recruited from the greater Providence, Rhode Island area in the United States. Recruitment methods included social media, physical advertisements, referrals from community health centers, housing shelters, other participants, and referrals from participant repositories of completed research studies at the Brown University Center for Alcohol and Addiction Studies. Study inclusion criteria were: (1) age of 21 years old or older; (2) past 6-month cigarette use; (3) smoking ≥ 5 cigarettes/day for 25 days or more in the last 30 days; (4) exhaled carbon monoxide of ≥6 ppm at Baseline; (5) household income < 250% federal poverty level (FPL) (chosen as this is the maximum income for most public benefits); (6) willingness to substitute combustible cigarettes for EC or NPs; (7) ability to read and write in English and (8) ownership of a cellular phone.

Study exclusion criteria were: (1) intention to quit smoking in the next 30 days with a set quit date; (2) current or past 30-day use of any smoking cessation method; (3) current use of EC or NP ≥ 4 days in the last month; (4) current self-report of primarily using tobacco products other than cigarettes; (5) positive urine pregnancy test; (6) hospitalization for a psychiatric issue in the past 30 days or visible instability; (7) other household member is a study participant; (8) participating in another clinical trial at the same time; (9) heart-related event in the past 30 days, and (10) planning to move out of the Providence area in the next 6 months. There was a change in the exclusion criteria after trial commencement. Initially, participants were excluded if they had any intention to quit in the next 30 days, even if they did not have a set quit date. This criterion changed to only exclude those with a set quit date to accurately exclude those who were seriously attempting to quit.

Randomization

Eligible participants who completed the Baseline questionnaire were randomly assigned in a 2:2:1 ratio to receive EC, nicotine pouches or to continue using their own cigarettes as usual. Randomization was conducted in this proportion to maximize exposure to ANDS and facilitate study retention. Participants were randomized using a computer-generated randomization program stratified by sex and age (<40; ≥40 years old). Randomization was conducted by the same research assistants who enrolled participants in the study, and both participants and research assistants were not blinded to the study condition.

Intervention

Participants randomized to the EC condition were provided with a complimentary VUSE Alto device and a 4-week supply of 5% nicotine e-liquid pods. Participants tried the e-liquid pods in the golden tobacco or menthol flavors at Baseline and chose their preferred flavor for the study. Participants received a second and final 4-week EC pod supply in the same flavor at week 4. A 4-week EC supply was calculated as a maximum of 32 pods, and this number was provided to ensure that EC participants had an adequate number of pods to fully substitute CC within a reasonable margin of error, considering that one pod is approximately equivalent to one pack of cigarettes. Participants in the EC group were not directly told not to smoke, rather they were instructed to replace all their cigarettes with e-cigarettes—ie to use the EC every time they wanted to smoke their cigarettes.

Participants randomized to the nicotine pouch condition were provided with a 4-week supply of complimentary on! 4 mg nicotine pouches. Participants tried the pouches in the original and mint flavors at Baseline and chose their preferred flavor for the study. Participants received a second and final 4-week nicotine pouch supply in the same flavor at week 4. A 4-week nicotine pouch supply was calculated as a maximum of 16 boxes with 20 pouches each, and this number was provided to ensure that participants had an adequate number of pouches to fully substitute combustible cigarettes within a reasonable margin of error, considering that one nicotine pouch is approximately equivalent to two cigarettes and one box (20 pouches) is equivalent to approximately two packs of cigarettes. Participants in the nicotine pouch group were not directly told not to smoke, rather they were instructed to replace all their cigarettes with nicotine pouches– ie to use the nicotine pouch every time they wanted to smoke their cigarettes.

Participants in the control condition received assessments only and all-groups were advised to quit smoking at the end of the study with a brief advice and a handout on how to contact the Quitline.

Outcomes and Measures

Study participants completed in-person assessments at Baseline, weeks 4 and 8, and phone assessments at weeks 1, 3, and 7. Compensation for time was $50 for all in-person visits and $25 for all other phone visits. Baseline measures included demographic characteristics; tobacco use history; cigarette dependence; respiratory symptoms measured with the American Thoracic Society Questionnaire (ATSQ)³⁷; measures of mood and mental health such as the PHQ-9 and GAD-7^38,39; and cannabis use measured with the revised Cannabis Use Disorder Identification Test (CUDIT-R).⁴⁰ Cigarette dependence was measured with 15 items from the Tobacco Dependence Index measure used in the Population Assessment of Tobacco and Health survey (possible range: 1–5 where higher scores mean higher dependence)^41–43; This measure compiles dependence items from commonly used dependence measures with the objective of creating a comprehensive dependence measure that can be used for different tobacco products. This measure has been validated and it is widely used.^42–45 This measure asks for the level of agreement with statements on a scale from 1— “not true of me at all” to 5— “extremely true of me.” Examples of statements include: “I find myself reaching for cigarettes without thinking about it,” “I frequently crave cigarettes,” and “my urges keep getting stronger if I don’t use cigarettes.” Clinical indicators such as height, weight, blood pressure, and urine for biomarker analysis (frozen for future analysis) were assessed. Adverse childhood experiences (ACE) were also measured as a count of the total ACEs reported, with a possible range of 0–10.

The primary outcome was the within-group change in cigarettes per day (CPD) from Baseline to week 8. CPD was calculated with a 7-day timeline followback (TLFB) at Baseline and week 8. Secondary outcomes included the within-group changes from Baseline to week 8 in cigarette dependence, CO levels, and cigarette abstinence. Cigarette abstinence at week 8 was defined as no CC use in the past 7 days, measured with the TLFB, and having exhaled CO < 6 ppm, assessed via Smokerlyzer. We also measured within-group changes in all-primary and secondary outcomes from Baseline to week 4.

Statistical Analysis

Sample size calculations were based on a similar EC switching study¹⁷ that showed a significant within-group change in CPD from Baseline to week 6 in the EC group (RR: 0.23, 95% CI: .18 to 0.30) (Cohen’s d = 0.8). There is no nicotine pouch-switching RCTs that can be used for sample size calculation. We expect that nicotine pouches will have a similar effect size as the EC, so we consider Cohen’s d = 0.8 for the sample size calculation. Considering 80% power and 20% attrition, the sample size of 18 individuals in the EC and nicotine pouch group is adequate to detect unadjusted within-group changes in mean CPD from Baseline to week 8. However, this pilot RCT is not powered to detect between-group, small within-group differences, or within-group differences in mean CPD from baseline to week 8 in the CC group.

Baseline characteristics were described by the study group. We assessed within-group differences in CPD, CC dependence and CO levels from Baseline to week 4 and week 8 using paired t test. Secondary post hoc analysis included between-group differences in study outcomes at weeks 4 and 8 tested with a two-sample t test between EC and CC groups, ONP and CC groups and EC and ONP groups; and differences in EC or nicotine pouch use trajectory by study group at weeks 4 and 8. Exclusive EC or nicotine pouch use was defined as any EC or nicotine pouch use and no CC use in the past 7 days and CO < 6 ppm. Dual use was defined as any EC or nicotine pouch use and any CC in the past 7 days or CO ≥ 6 ppm. Exclusive CC use was defined as no EC or nicotine pouch use and any CC use in the past 7 days. All-analyses were conducted with completers only (weeks 4 and 8 completers, respectively).

The analyses were performed using Stata 17 SE (College Station, TX). Statistical significance was set at .05 with two-sided p-values.

Sensitivity Analysis

The primary statistical analyses were conducted with complete cases only. This may introduce bias.⁴⁶ Thus, we conducted a sensitivity analysis of the within-group differences in CPD, CC dependence and CO levels from Baseline to week 8 using inverse probability weights (IPWs). IPWs help account for the attrition bias because their calculation includes the probability of being in the study at week 8 as a function of baseline variables that also impact missing.⁴⁶ More details on the sensitivity analysis methods and results are available in the Appendix.

Results

Participants were recruited between March 2022 and December 2022, and follow-up was completed through February 2023. Of the 203 individuals screened for eligibility, nine were randomized to continue to smoke cigarettes, 18 to switch to EC, and 18 to switch to nicotine pouches (Figure 1). In the control, EC and nicotine pouch groups, seven (77.8%), 14 (77.8%), and 12 (66.8%) participants, respectively, attended the primary outcome week 8 visit. One participant in the nicotine pouch group withdrew from the study after randomization. Participants lost to follow-up at week 8 were more likely than those who returned to be men, to have lower education, to be non-menthol users, and to have lower Baseline CO. Attrition was greater in the nicotine pouch arm (29.4% at week 8) compared to the EC or CC groups (22.2% at week 8 for both) (p-value = .9).

Figure 1.

Participant recruitment flowchart. (a) Includes participants in multiple categories.

Definitions: CO: carbon monoxide; EC: electronic cigarettes; FPL: federal poverty level; ONP: oral nicotine pouches.

The mean study age was 50.1 years (SD: 10.7) and 16 participants were women (36.4%). 68.2% of participants had a high school education or less and 77.3% had Medicaid insurance. The median household income was $14 400 (IQR: $10 000–$30 000). Participants smoked an average of 13.9 CPD at Baseline (SD: 10.1) and 79.5% used their CC within the first 30 min of waking up. Additional Baseline characteristics are shown in Table 1.

Table 1.

Baseline Characteristics of Study Participants

Baseline characteristics, N (%)	All (N = 45)	EC (N = 18)	Nicotine pouch (N = 18)	CC (N = 9)
Mean age (SD)	50.1 (10.7)	52.5 (9.9)	46.9 (11.3)	51.2 (11.0)
Women	16 (36.4)	7 (38.9)	6 (35.3)	3 (33.3)
Race
White	22 (52.4)	9 (52.9)	8 (50.0)	5 (55.6)
Black or African American	8 (19.0)	4 (23.5)	3 (18.8)	1 (11.1)
Other/multiracial	12 (28.6)	4 (23.5)	5 (31.2)	3 (33.3)
Latino	6 (13.6)	2 (11.1)	3 (17.6)	1 (11.1)
High school education or less	30 (68.2)	14 (77.8)	11 (64.7)	5 (55.6)
Medicaid insurance	34 (77.3)	15 (83.3)	14 (82.4)	5 (55.6)
ACE score, mean (SD) (possible range: 0–10)	3.4 (2.9)	3.3 (2.3)	4.1 (3.4)	2.4 (2.8)
Menthol smoker	29 (65.9)	15 (83.3)	10 (58.8)	4 (44.4)
Duration of smoking, years, mean (SD)	21.9 (13.7)	22.1 (14.2)	21.3 (13.3)	22.5 (14.9)
Time to first cigarette ≤ 30 min	35 (79.5)	13 (72.2)	14 (82.4)	8 (88.9)
Cigarettes per day in the past 7 days, mean (SD)	13.9 (10.1)	14.4 (7.1)	14.8 (13.1)	11.4 (9.1)
Carbon monoxide, mean (SD)	31.6 (18.9)	29.1 (4.2)	34.9 (4.5)	30.1 (7.4)
CC dependence, mean (SD) (Possible range: 1–5)	3.2 (0.9)	3.0 (0.8)	3.3 (1.0)	3.7 (0.6)

Definitions: ACE: adverse childhood experiences; CC: combusted cigarettes; EC: electronic cigarettes.

There were significant within-group differences in CPD (primary outcome) between Baseline and week 8 in both the EC and nicotine pouch groups (Table 2). For those in the EC group, average CPD decreased from 14.72 at Baseline to 2.94 by week 8 (p-value < .001). For those in the nicotine pouch group, average CPD decreased from 14.98 to 8.26 by week 8 (p-value = .01). CPD did not decrease significantly for those in the CC control group by week 8. Mean cigarette dependence also significantly decreased by week 8 for those in the EC and nicotine pouch groups and mean CO levels significantly decreased from Baseline to week 8 for those in the EC group (Table 2). Similar results were observed for CPD at week 4. However, there were no significant changes in cigarette dependence or CO at week 4. There were no significant between-group differences in CPD, CC dependence or CO levels at weeks 4 or 8.

Table 2.

Within-Group Changes in Primary and Secondary Outcomes from Baseline to week 4 and week 8 (completers only)

Week 4
	EC Arm (N = 17)			ONP Arm (N = 14)			CC Arm (N = 8)
Mean (95% CI)	Baseline	Week 4	p-Value	Baseline	Week 4	p-Value	Baseline	Week 4	p-Value
CPD	14.76 (11.07; 18.43)	4.40 (1.76; 7.04)	<.001	14.75 (6.42; 23.10)	9.24 (3.53; 14.96)	.04	10.33 (2.74; 17.93)	13.79 (1.96; 25.6)	.5
CC dependence*	3.03 (2.60; 3.47)	2.80 (2.19; 3.40)	.2	3.22 (2.60; 3.84)	3.18 (2.54; 3.82)	.7	3.70 (3.14; 4.27)	3.52 (2.84; 4.19)	.2
CO levels**	29.81 (19.69; 39.93)	20.31 (12.79; 27.84)	.1	33.35 (22.05; 44.66)	33.0 (18.42; 47.58)	.9	30.5 (10.73; 50.27)	28.25 (8.85; 47.64)	.6
Week 8
	EC Arm (N = 14)			ONP Arm (N = 12)			CC Arm (N = 7)
Mean (95% CI)	Baseline	Week 8	p-Value	Baseline	Week 8	p-Value	Baseline	Week 8	p-Value
CPD	14.72 (10.32; 19.12)	2.94 (0.09; 5.79)	<.001	14.98 (5.02; 24.93)	8.26 (1.34; 15.18)	.01	11. 82 (3.76; 19.87)	9.33 (–0.05; 18.71)	.1
CC dependence	3.10 (2.64; 3.56)	2.68 (2.17; 3.18)	.02	3.10 (2.48; 3.73)	2.42 (1.72; 3.11)	.02	3.61 (2.99; 4.22)	3.30 (2.46; 4.14)	.2
CO levels	29.5 (18.39; 40.61)	14.14 (7.03; 21.25)	.03	35.0 (21.33; 48.67)	32.08 (10.28; 53.88)	.6	32.71 (9.93; 55.50)	41.43 (–1.30; 84.16)	.4

^*Sample size for Nicotine Pouch arm is 13 at week 4; **Sample size for EC arm is 16 at week 4.

Bolding indicates statistical differences between Baseline and weeks 4 or 8.

Definitions: CC: combusted cigarettes; CO: carbon monoxide; CPD: cigarettes per day; EC: electronic cigarettes; ONP: oral nicotine pouch.

The EC and nicotine pouch use trajectory from the secondary post hoc analysis is shown in Table 3. In the EC group, 28.6% exclusively used EC at week 8 (n = 4). In the EC arm, the one person who remained exclusively using CC (CO level: 13.0) and those who had dual use (M: 19.5, SD: 11.9, [n = 9]) had higher CO levels than those who exclusively used EC at week 8 (M: 2.2, SD: 0.96) (p-value < .01 for both post hoc comparisons). There was no significant difference in CO levels between those with exclusive CC use and those with dual use. In the nicotine pouch group, 8.3% exclusively used nicotine pouch at week 8 (n = 1). There was a similar difference in CO levels for those in the nicotine pouch group in week 8. Those who remained exclusively using CC (M: 26.6, SD: 15.5, [n = 3]) and those who had dual use (M: 37.6, SD: 40.3, [n = 8]) had higher CO levels than those who exclusively used nicotine pouches at week 8 (M: 4.0, SD: 0) (p-value < .01 for both comparisons). There were no differences in CO levels between exclusive CC users and dual users (Table 3).

Table 3.

EC and ONP Use Trajectory and Corresponding Cigarette Dependence and Carbon Monoxide Levels at Weeks 4 and 8 (completers only)

	EC arm				ONP arm
	N (%)	Mean CPD (SD)	Mean CC dependence (SD)	Mean CO level (SD)	N (%)	Mean CPD (SD)	Mean CC dependence (SD)	Mean CO level (SD)
		Week 4
Exclusive CC use	1/17 (5.9)	1.07 (0)	1.06 (0) +	22.0 (0)	0/14(0.0)	-	-	-
Dual use	16/17 (94.1)	4.61 (5.2)	2.91 (1.1)	20.2 (14.6)	14/14 (100.0)	9.24 (9.9)	3.18 (0)	33.0 (25.2)
Exclusive EC or nicotine pouch use	0/17 (0.0)	–	–	–	0/14 (0.0)	–	–	–
		Week 8
Exclusive CC use	1/14 (7.14)	3.57 (0)	2.38 (0)	13.0 (0)	3/12 (25.0)	6.62 (3.8)	2.27 (1.1)	26.67 (15.5)
Dual use	9/14 (64.3)	3.65 (4.5)	2.72 (0.7)	19.55 (11.9) ++	8/12 (66.7)	9.91 (13.0)	2.66 (1.1) ++	37.63 (40.3) ++
Exclusive EC or nicotine pouch use	4/14 (28.6)	–	2.66 (1.4)	2.25 (0.9) +++	1/12 (8.3)	–	0.94 (0)	4.0 (0) +++

Exclusive EC/NP use: any EC/NP use and no CC use in the past 7 days and CO < 6 ppm. Dual use: any EC/NP use and any CC in the past 7 days or CO ≥ 6 ppm. Exclusive CC use: no EC/NP use and any CC use in the past 7 days.

Post hoc comparisons between exclusive CC use, dual use and exclusive EC or Nicotine Pouch use within arm: ⁺p-value < .05 for exclusive CC use vs. dual use comparison, ⁺⁺p-value < .05 for dual use vs. exclusive product use comparison, and ⁺⁺⁺p-value < 0.05 for exclusive CC use vs. exclusive product use comparison.

Definitions: CC: combusted cigarettes; CO: carbon monoxide; CPD: cigarettes per day; EC: electronic cigarettes; ONP: oral nicotine pouch.

There were no serious adverse effects reported. Participants in the nicotine pouch group were more likely to report having a cough throughout the day and shortness of breath when exercising or walking up the stairs every day in the first week of the intervention period (N = 5 for cough and N = 6 for shortness of breath) than those in the EC group (N = 3 for cough and N = 1 for shortness of breath). The frequency of cough and shortness of breath decreased and became similar across groups by week 4.

Discussion

This pilot RCT tested the effects of 8-weeks of EC or nicotine pouch use on CPD, CC dependence, CO levels, and complete CC substitution among low SES adults who smoke. Findings showed a significant reduction in the primary outcome of CPD from Baseline to week 8 for those randomized to the EC and nicotine pouch groups. Both intervention groups also had a significant reduction in CC dependence between Baseline and week 8. CPD and CC dependence did not significantly change in the CC control group. There were no significant differences between EC and nicotine pouch conditions; the study was not powered to test between-group differences.

EC seemed to have a great potential to decrease CPD and to help individuals who smoke and were not willing to quit smoking to completely switch from CC to EC, as shown in other studies.^17,18,47 A recent study among people who smoke with serious mental illness who were asked to switch to disposable EC demonstrated a similar within-group decrease in mean CPD from Baseline to week 8 (Mean:18.1 [95% CI: 16.4 to 19.8] to 8.2 [6.6–9.9], respectively).⁴⁷ Another 4^th generation EC switching RCT also showed a similar proportion of exclusive EC use at the week 6 follow-up (28.1%)¹⁷ as the one observed at our week 8 follow-up (28.6%), which may be because both studies used similar EC products. However, the proportion of individuals who continued to exclusively smoke cigarettes and did not use EC in their study was higher than the one observed in our study (14% in their study at week 6 vs. 7.1% in our study at week 8).¹⁷

Using nicotine pouches for 8 weeks also significantly decreased CPD and CC dependence. A non-randomized prospective study among adult smokers also observed that using 4mg nicotine pouches for 6 weeks significantly decreased CPD, where 16% of participants had greater than 50% CPD reduction from Baseline to week 6.⁴⁸ Although not significantly different, the observational differences in CPD and CO-verified cigarette abstinence between EC and nicotine pouches show that nicotine pouches may not necessarily substitute CC to the same extent as EC. Only one individual completely switched from CC to nicotine pouches and 3 individuals stopped using nicotine pouches during the study, with the majority remaining as dual users. First, nicotine pouches may not elicit a similar behavioral process as CC because it is an oral smokeless product. In contrast, EC is an inhaled product, that has an oral ritual, hand-to-mouth motion and throat sensation similar to that of CCs, which may facilitate substitution. Second, participants in the nicotine pouch group needed to be educated about the product because they assumed that nicotine pouches were chewing tobacco or SNUS and were hesitant to use the product due to perceived risks about these products (results from qualitative study forthcoming). They also reported difficulty getting used to the strength of nicotine content in the first days.

This study is one of the first to assess a harm-reduction approach for individuals with lower SES who smoke. Overall, our results showed that both EC and nicotine pouches have a harm-reduction potential for this at-risk population. Thus, EC and nicotine pouches may help reduce tobacco-related disparities. When considering a harm-reduction approach, ANDS need to be accessible and affordable for individuals with lower SES. Education about tobacco harm reduction is also needed to inform about the different risks of tobacco products.

Limitations

This study has limitations. First, this study is not powered for between-group comparison and a larger fully powered RCT is needed to test the acceptability and harm-reduction potential of nicotine pouches compared to CC. Second, this study only observed product use for 8 weeks and a longer follow-up is needed to assess if product use, especially nicotine pouches, will be sustainable over time. Third, participants did not return used or unused products, so there is potential for recall bias on how many EC pods and nicotine pouches they used per week. There is not a gold-standard measure to assess actual EC use quantity and thus, EC use was not quantified. Fourth, the loss to follow-up in our sample was significant and more than what we estimated in the power analysis. Our study population did not have stable access to a cellular phone (the primary form of contact in our study) or housing in some cases, leading to difficulties with study follow-up. Despite this limitation, the sensitivity analyses confirmed the robustness of our findings. Fifth, urine or blood biomarkers of tobacco harm and exposure are important to assess the potential harm-reduction effect of EC and nicotine pouches and were not included in this study. Finally, participants were paid with products and money, impacting the generalizability of study findings to other adults with low SES.

Conclusions

This pilot RCT found that low SES participants who used EC or nicotine pouches for 8 weeks had significantly lower CPD and CC Dependence compared to Baseline. Those in the EC group also had significantly lower CO levels compared to the Baseline. Further, 28.6% of those in the EC group and 8.3% of those in the nicotine pouch group fully switched off cigarettes. Overall, both EC and nicotine pouches may be harm reduction tools for individuals who smoke, have lower SES and are not willing or unable to quit smoking.

Funding

The study is funded by the Brown University Office of Vice President Research. The authors JCA, DDM, and JSA are partially or fully funded by an NIH-funded Center of Biomedical Research Excellence (COBRE) (P20GM130414).

Declaration of Interests

JSA serves as a consultant and has equity in the start-up company Qnovia. This is a start-up company developing smoking cessation prescription medications through the FDA. They currently do not have a product that is available for sale. The other authors have no conflict of interest to disclose.

Author Contributions

Jaqueline Avila (Conceptualization [equal], Data curation [equal], Formal analysis [lead], Investigation [lead], Methodology [lead], Project administration [lead], Software [equal], Supervision [equal], Visualization [Lead], Writing—original draft [lead], Writing—review & editing [lead]), Dale Dagar Maglalang (Investigation [equal], Methodology [equal], Project administration [equal], Supervision [equal], Writing—original draft [equal], Writing—review & editing [equal]), Nicole Nollen (Conceptualization [equal], Formal analysis [equal], Investigation [equal], Methodology [equal], Supervision [equal], Visualization [equal], Writing—original draft [equal], Writing—review & editing [equal]), Sangah Lee (Formal analysis [supporting], Investigation [supporting], Methodology [equal], Project administration [supporting], Writing—original draft [equal], Writing—review & editing [equal]), Riley Suh (Formal analysis [supporting], Methodology [supporting], Project administration [supporting], Writing—original draft [equal], Writing—review & editing [equal]), Mona Malone (Investigation [supporting], Methodology [supporting], Project administration [supporting], Visualization [equal], Writing—original draft [equal], Writing—review & editing [equal]), Urvi Binjrajka (Investigation [supporting], Methodology [supporting], Project administration [supporting], Writing—original draft [equal], Writing—review & editing [equal]), and Jasjit Ahluwalia (Conceptualization [lead], Funding acquisition [lead], Investigation [lead], Methodology [equal], Project administration [equal], Resources [lead], Supervision [lead], Validation [equal], Visualization [equal], Writing—original draft [equal], Writing—review & editing [equal]).

Data Availability

The data underlying this article will be shared on reasonable request to the corresponding author.