Effectiveness of Oral Nicotine Pouches as a Cessation Tool Among Adult Tobacco Users in Pakistan

This randomized controlled trial aims to evaluate the effectiveness of 6 mg Velo® oral nicotine pouches, available in Polar Mint and Berry Frost flavors, when combined with structured motivational counselling for smoking cessation among adult tobacco users in Pakistan. The study will compare this combined intervention with motivational counselling alone to determine whether ONPs improve smoking cessation outcomes.

Participants will be recruited from Premium Medical Complex, Rawalpindi. Eligible adult smokers who meet the inclusion criteria will be randomly assigned in a 1:1 ratio to either the intervention group or the control group. Participants in the intervention group will receive oral nicotine pouches in addition to standardized motivational counselling, while participants in the control group will receive the same counselling program without nicotine pouches. The intervention period will last 12 weeks.

Throughout the study, participants will undergo regular clinical assessments to monitor smoking status, nicotine cravings, withdrawal symptoms, treatment adherence, participant satisfaction and safety. Smoking abstinence will be objectively verified using carbon monoxide breath testing in addition to participant self-report. Standardized and validated assessment tools will be used to evaluate craving intensity, withdrawal symptoms, treatment satisfaction and medication adherence.

Motivational counselling will be delivered using a structured, evidence-based approach incorporating motivational interviewing, goal setting, coping strategies, positive reinforcement and relapse prevention techniques. These counselling sessions are intended to enhance participants' motivation, strengthen self-efficacy, improve adherence to the intervention and support long-term smoking cessation.

Safety will be monitored throughout the trial by recording adverse events, monitoring vital signs, and documenting any nicotine-related side effects or product tolerability issues. Participant confidentiality will be maintained in accordance with Good Clinical Practice (GCP), International Council for Harmonisation (ICH) guidelines and the Declaration of Helsinki.

The findings of this study will provide the first randomized clinical evidence from Pakistan regarding the effectiveness, safety, adherence, and acceptability of oral nicotine pouches as a smoking cessation aid. The results are expected to inform future tobacco harm reduction policies, smoking cessation programs and clinical practice in Pakistan and other low- and middle-income countries with similar tobacco use patterns.

• Velo 6 mg Oral Nicotine Pouches (Other): Participants receive commercially available 6 mg Velo oral nicotine pouches (Polar Mint or Berry Frost). The daily dose ranges from 1 to 3 pouches based on individual nicotine requirements, craving relief, withdrawal symptoms, tolerability and adherence during the 12-week intervention period.
• Motivational Counselling (Behavioral): Participants receive structured group-based motivational counselling consisting of five sessions over 12 weeks. The counselling includes motivational interviewing, psychoeducation, SMART goal setting, coping strategies, stress management, positive reinforcement, peer support and relapse prevention to support smoking cessation.

Primary outcomes

• Biochemically Verified Smoking Cessation Rate [12 weeks]: The proportion of participants who achieve smoking cessation, verified by carbon monoxide (CO) breath testing together with self-reported abstinence. ≥30% of participants in the intervention group are expected to achieve biochemically verified smoking abstinence (carbon monoxide \[CO\] level <6 ppm) by Week 12, compared with ≤10% of participants in the control group.
• Reduction in Daily Cigarette Consumption [Baseline to Week 12]: Change in the average number of cigarettes smoked per day from baseline to Week 12, based on participant self-report. Reduce cigarette consumption by ≥30% from baseline. The mean daily cigarette consumption is expected to decrease from approximately 15 cigarettes per day at baseline to ≤7 cigarettes per day by Week 12 in the oral nicotine pouch intervention group, compared with a ≤20% reduction in the motivational counselling-only control group.

Secondary outcomes

• Change in Cigarette Craving Intensity [Baseline, Weeks 2, 4, 8, and 12]: Change in cigarette craving intensity from baseline, measured using the Visual Analogue Scale for Cigarette Craving. Participants rate their current craving for a cigarette on a scale ranging from 0 to 10, where 0 indicates no craving and 10 indicates the strongest possible craving. Higher scores indicate greater cigarette craving and therefore a worse outcome. Changes in craving scores will be compared between the oral nicotine pouch intervention group and the motivational counselling-only control group.
• Change in Nicotine Withdrawal Symptoms [Weeks 2, 4, 8, and 12]: Change in nicotine withdrawal symptoms measured using the Minnesota Nicotine Withdrawal Scale (MNWS). The scale assesses the severity of nicotine withdrawal symptoms, with individual symptoms rated from 0 (not present) to 4 (severe). Item scores are summed to generate a total withdrawal symptom score. Higher scores indicate greater severity of nicotine withdrawal symptoms and therefore a worse outcome.
• Medication Adherence Report Scale Score [Weeks 2, 4, 8, and 12]: Treatment adherence assessed using the 5-item Medication Adherence Report Scale (MARS-5). Each item is rated on a 5-point response scale, producing a total score ranging from 5 to 25. Higher scores indicate greater medication adherence and therefore a better outcome.
• Treatment Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication Version 1.4 [Weeks 2, 4, 8, and 12]: Treatment satisfaction will be assessed using the Treatment Satisfaction Questionnaire for Medication, Version 1.4 (TSQM-1.4). The questionnaire assesses treatment satisfaction across the domains of effectiveness, side effects, convenience, and global satisfaction. Domain scores are transformed to a scale ranging from 0 to 100, with higher scores indicating greater treatment satisfaction and therefore a better outcome.
• Incidence of Adverse Events [Baseline to Week 12]: Number of participants experiencing treatment-emergent adverse events related to oral nicotine pouch use during the study.
• Adherence to Assigned Oral Nicotine Pouch Use [Weeks 2, 4, 8, and 12]: Adherence to assigned oral nicotine pouch use will be assessed using participant-reported use records/diaries. Adherence will be calculated as the percentage of prescribed oral nicotine pouches used during the assessment period. The outcome will be reported as a percentage from 0% to 100%, with higher percentages indicating greater adherence.

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Adult smokers aged 18 to 65 years.
* Currently smoke 10 to 14 cigarettes per day.
* Express a willingness to quit smoking.
* Have no prior experience using oral nicotine pouches.
* Have no contraindications to nicotine use.
* Able and willing to provide written informed consent.
* Able and willing to comply with all study procedures and follow-up assessments.

Exclusion Criteria:

* Pregnant or breastfeeding women.
* Individuals with severe cardiovascular disease or other conditions that make nicotine use unsafe.
* Participants currently enrolled in another smoking cessation program or clinical trial.
* Individuals with known allergy or hypersensitivity to nicotine or any component of the oral nicotine pouches.
* Individuals with a history of significant psychiatric disorders that may interfere with study participation.
* Individuals unable or unwilling to comply with study procedures or follow-up visits.

• Madeeha Malik, Principal investigator, Cyntax Health Projects PVT LTD