Condition category
Respiratory
Date applied
22/11/2017
Date assigned
28/11/2017
Last edited
07/03/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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 the 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?
July 2017 to May 2018

Who is funding the study?
Swedish Match North Europe (Sweden)

Who is the main contact?
Mikael Staaf
mikael.staaf@swedishmatch.com

Trial website

Contact information

Type

Scientific

Primary contact

Dr Mikael Staaf

ORCID ID

Contact details

Swedish Match North Europe
Maria Skolgata 83
Stockholm
SE-118 53
Sweden

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

SM 17-02

Study 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

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

EPN Gothenburg, 24/10/2017, ref: Dnr 778-17

Study design

Part 1: Single centre open randomised four-way crossover single administration trial including 20 subjects
Part 2: Singlecentre open observational follow-up study during 6 weeks including 60 subjects

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Other

Patient information sheet

Not available in web format, please use the contact details to request a patient information.

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

Phase

Drug names

Primary outcome measures

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 trial start date

06/07/2017

Overall trial end date

31/05/2018

Reason abandoned

Eligibility

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 type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

Part 1: 20 Part 2: 60

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

30/10/2017

Recruitment end date

30/03/2018

Locations

Countries of recruitment

Sweden

Trial participating centre

CTC Clinical Trial Consultants AB
SE-752 37
Sweden

Sponsor information

Organisation

Swedish Match North Europe

Sponsor details

Maria Skolgata 83
Stockholm
SE-118 53
Sweden

Sponsor type

Industry

Website

Funders

Funder type

Industry

Funder name

Swedish Match North Europe

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a peer reviewed journal.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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.