An open observational study investigating the effect on oral health when using tobacco free nicotine pods
| ISRCTN | ISRCTN16087707 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16087707 |
| Secondary identifying numbers | SM 17-02 |
- Submission date
- 22/11/2017
- Registration date
- 28/11/2017
- Last edited
- 12/02/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English Summary
Background and study aims
Snus is a moist form of smokeless tobacco which is usually placed under the upper lip. It is sometimes used as a last resort for people who have failed stopping smoking with the available pharmaceutical smoking cessation aids. Clinical experience does not show that habitual use of regular, tobacco based snus affects biofilm acidogenicity (the acid levels of the cells that line a surface in the mouth). Contributing factors may be that snus includes food approved pH
regulating substances (such as sodium carbonate) which maintains a relatively high pH in the
snus pinch/pouch (c. pH 8-8.5), nicotine itself does not seem to affect biofilm acidogenicity,
Nicotine itself does not seem to affect biofilm acidogenicity, and that the tobacco does not function as a substrate for the oral microflora. These circumstances may help to explain why caries does not seem to be more prevalent among snus users than among non-tobacco users. The non-tobacco based nicotine pouch (ZYN®) is an alternative form of orally delivered nicotine. The physical properties of ZYN® in terms of pH (aciditiy levels) is the same as with regular, tobacco-based snus and the product is used the same way, that is, it is placed in the upper sulcus for 30-60 minutes. However, the matrix for the nicotine in ZYN® is different from that in regular snus: microcrystals of maltitol and cellulose instead of ground tobacco leaves. In food stuffs, maltitol and cellulose have not been associated with changes in biofilm acidogenicity. However, the prolonged exposure (c. 30-60 minutes) associated with use in a product like ZYN® constitutes a somewhat different type of exposure. The aim of this study is to assess if the use of ZYN® will adversely affect biofilm acidogenicity.
Who can participate?
Adults aged 19 and older who are Snus users.
What does the study involve?
This study contains two parts. In the first part, participants are randomly allocated as to what order they receive the following: ZYN® Smooth 3 mg, ZYN® Peppermint 3 mg, 10% sucrose and 10% xylitol. These are single doses and are put between the upper lip and the gum for 60 minutes. In the second part of the study, participants can choose from 3 or 6 mg pouches of ZYN® Smooth, ZYN® Peppermint or ZYN® Cinnamon. Participants use these for six weeks and report to the clinic every other week for oral assessments.
What are the possible benefits and risks of participating?
There are no possible benefits of participating. The tested products are commercially available and only participants who are well acquainted with and used to the effects of nicotine will participate. The only side effects are the effects likely to be related to nicotine exposure (such as salivation, nausea, and dyspepsia).
Where is the study run from?
TC Clinical Trial Consultants AB (Sweden)
When is the study starting and how long is it expected to run for?
September 2017 to March 2019
Who is funding the study?
Swedish Match North Europe (Sweden)
Who is the main contact?
Camilla Pramfalk
Camilla.Pramfalk@swedishmatch.com
Contact information
Scientific
Swedish Match North Europe
Maria Skolgata 83
Stockholm
SE-118 53
Sweden
| Phone | +46 76 111 35 13 |
|---|---|
| Camilla.Pramfalk@swedishmatch.com |
Study information
| Study design | Part 1: Single-centre open randomized four-way crossover single administration trial including 20 subjects Part 2: Single-centre open observational follow-up study during 6 weeks including 60 subjects |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Other |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information. |
| Scientific title | Oral Safety Study: Open observational study of oral health associated with use of a non-tobacco based nicotine pouch (ZYN®) among current daily snus users |
| Study acronym | OSS |
| Study hypothesis | Clinical experience does not indicate that habitual use of regular, tobacco based snus affects biofilm acidogenicity. Although there are no priori reasons to believe that use of a non-tobacco based nicotine pouch will adversely affect biofilm acidogenicity, it is reasonable to rigorously assess this possibility in the context of a controlled clinical trial. |
| Ethics approval(s) | EPN Gothenburg, 24/10/2017, ref: Dnr 778-17 |
| Condition | ICD-10 code Z72: ”Tobacco use not otherwise specified (NOS)” |
| Intervention | This study contains two parts. The first part of the study assessed the dental plaque acidogenicity after short-term exposure to study protocols. Part 1: Participants are randomly allocated in four ways in this cross over trial: 1. ZYN® Smooth 3 mg 2. ZYN® Peppermint 3 mg 3. 10% sucrose 4. 10% xylitol The treatments are administered as single doses in a pre-determined computer-generated randomized order according to a four sequence list. The subject keeps the pouch still between the upper lip and the gum for 60 minutes. The duration of the treatments and follow-up takes approximately 30 days. Part 2: Ad libitum use of a ZYN® nicotine pouch, participants can choose from 3 or 6 mg pouches of ZYN® Smooth, ZYN® Peppermint or ZYN® Cinnamon. The treatments are administered as ad libitum use during 6 weeks. Subjects will report to the clinic every second week for oral assessments. Each visit takes approximately 75 minutes. |
| Intervention type | Other |
| Primary outcome measure | Assessment of dental plaque acidogenicity, using the pH microtouch method, during exposure of nicotine pouch at baseline, one, two, 5, 10, 20, 30, 40, 50 and 60 minutes. |
| Secondary outcome measures | 1. Adverse events are measured using patient interviews at screening, 0, 7, 14, 21 and 28 days (Part 1) or screening, baseline, 14, 28, 42 and 49 days (Part 2) 2. Oral microflora is measured using plaque sampling with a sterile toothpick from the buccal areas of respective quadrants at screening, 14, 28 and 42 days (Part 2) 3. Oral mucosa and pathological changes are recorded using the four-grade clinical scale measured using at screening, 14, 28 and 42 days (Part 2) |
| Overall study start date | 14/09/2017 |
| Overall study end date | 21/03/2019 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Part 1: 20 Part 2: 60 |
| Total final enrolment | 79 |
| Participant inclusion criteria | 1. Snus user, with a minimum weekly consumption of three or more snus cans (brands with nicotine content <1%) or two or more cans (brands with nicotine content >1%) since ≥1 year 2. Consent to participate voluntarily and sign Informed Consent Form prior to any study procedure 3. Healthy male/female, age ≥19. Female subjects should have a negative pregnancy test 4. Willing and able to comply with study procedures 5. Normal stimulated salivary secretion rate (>0.7 ml/min) |
| Participant exclusion criteria | 1. A history or presence of diagnosed hypertension or any cardiovascular disease 2. Surgery within 6 months of the screening visit that, in the opinion of the investigator, could negatively impact on the subject’s participation in the clinical study 3. Any surgical or medical condition, which, in the judgment of the clinical investigator, might interfere with the absorption, distribution, metabolism or excretion of nicotine 4. Subjects who are pregnant 5. Allergy towards composite materials 6. Antibiotic use during or within the last 4 weeks prior to the study period |
| Recruitment start date | 06/11/2017 |
| Recruitment end date | 05/06/2018 |
Locations
Countries of recruitment
- Sweden
Study participating centre
Sweden
Sponsor information
Industry
Maria Skolgata 83
Stockholm
SE-118 53
Sweden
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 30/06/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a peer reviewed journal. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Interim results article | Effects on mucosal lesions and cytokine levels | 19/07/2022 | 25/07/2022 | Yes | No |
| Protocol file | version 1.0 | 14/09/2017 | 01/12/2022 | No | No |
| Other unpublished results | clinical study report | 21/03/2019 | 12/02/2024 | No | No |
Additional files
Editorial Notes
12/02/2024: A clinical study report was uploaded as an additional file.
07/12/2022: The intention to publish date was changed from 31/12/2022 to 30/06/2023.
01/12/2022: Uploaded protocol (not peer reviewed).
25/07/2022: Publication reference added.
08/12/2021: The intention to publish date has been changed from 31/12/2021 to 31/12/2022.
14/04/2021: The following changes were made to the trial record:
1. The overall trial start date was changed from 06/07/2017 to 14/09/2017.
2. The recruitment start date was changed from 30/10/2017 to 06/11/2017.
3. The recruitment end date was changed from 31/05/2018 to 05/06/2018.
4. The overall trial end date was changed from 25/03/2019 to 21/03/2019.
5. The intention to publish date was changed from 30/06/2021 to 31/12/2021.
6. The contact details were updated.
02/12/2020: The intention to publish date was changed from 30/06/2020 to 30/06/2021.
31/03/2020: The following changes were made to the trial record:
1. The intention to publish date was changed from 25/03/2020 to 30/06/2020.
2. The total final enrolment was added.
09/07/2019: The following changes were made to the trial record:
1. The overall end date was changed from 31/07/2018 to 25/03/2019.
2. the intention to publish date was added.
16/08/2018: The following changes have been made to the trial record:
1. The overall trial end date has been changed from 31/05/2018 to 31/08/2018
2. The intervention type has been added
3. The recruitment end date has been changed from 30/03/2018 to 31/05/2018
07/03/2018: Plain English Summary has been updated in line with the updated overall trial end date.
05/03/2018: Recruitment end date was changed from 15/02/2018 to 30/03/2018. The overall trial end date was changed from 30/04/2018 to 31/05/2018.
17/01/2018: Recruitment end date was changed from 01/12/2017 to 15/02/2018. The overall trial end date was changed from 31/03/2018 to 30/04/2018.
