In-vivo Extraction of Lead, Cadmium and Tobacco Specific Nitrosamines From Swedish 'Snus' in Regular Snus Users

Study Overview
=================
Brief Summary
-----------------
In an open label, randomized, two-way cross-over study, 32 male healthy regular snus users will be given repeated doses of four different types of portion snus: General, Catch, Catch Mini and Catch Dry Mini. Each portion of used snus will be collected and frozen (-20 oC) pending analysis of lead (Pb), cadmium (Cd), nicotine and tobacco specific nitrosamines (TSNAs). Unused snus is collected and deep frozen for analysis and calculation of extracted dose. Calculations of extracted amount of lead, cadmium, nicotine and tobacco specific nitrosamines (TSNAs) respectively, will be done for each type of snus.

Detailed Description
-----------------
Comparisons: A= General Portion 1 g portion snus containing approximately 8 mg nicotine per portion. B= Catch Licorice Portion 1 g portion snus containing approximately 8 mg nicotine per portion. C= Catch Licorice Portion Mini 0.5 g portion snus containing approximately 4 mg nicotine per portion. D= Catch Dry Licorice Portion Mini 0.3 g portion snus containing approximately 4 mg nicotine per portion. Swedish portion snus will be administered once every hour (4 administrations/brand) and will be kept between the upper lip and the gum for 30 minutes. Preload of own brand each morning.

Official Title
-----------------
In-vivo Extraction of Lead, Cadmium and Tobacco Specific Nitrosamines From Four Brands of Swedish 'Snus' in Regular Snus Users.

Conditions
-----------------
Smoking Cessation, Harm Reduction

Intervention / Treatment
-----------------
* Procedure: Buccal Administration of nicotine
* Procedure: Buccal Administration of nicotine
* Procedure: Buccal Administration of nicotine
* Procedure: Buccal Administration of nicotine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: non-smokers, 18 to 50 years of age. Habitual use of > 7 portions snus daily since minimum 1 year. Healthy according to the health declaration and interview. Written informed consent given. Exclusion Criteria: Concurrent participation in another clinical trial. History of allergy. History of allergy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: General 1 g pouch<br>Oral pouch 0.3-1g, single dose. One pouch administered over 30 minutes. Buccal Administration of nicotine. | Procedure: Buccal Administration of nicotine<br>* Oral pouch 1g, single dose. One pouch administered over 30 minutes.<br>* Other names: PREP;|
| Active Comparator: Catch Licoice 1 g pouch<br>Oral pouch 1g, single dose. One pouch administered over 30 minutes. Buccal Administration of nicotine. | Procedure: Buccal Administration of nicotine<br>* Oral pouch 1g, single dose. One pouch administered over 30 minutes.<br>* Other names: PREP;|
| Active Comparator: Catch Licorice Mini 0.5 g pouch<br>Oral pouch 0.5g, single dose. One pouch administered over 30 minutes. Buccal Administration of nicotine. | Procedure: Buccal Administration of nicotine<br>* Oral pouch 0.5 g, single dose. One pouch administered over 30 minutes.<br>* Other names: PREP;|
| Active Comparator: Catch Licorice dry mini 0.3 g pouch<br>Oral pouch 0.3 g, single dose. One pouch administered over 30 minutes. Buccal Administration of nicotine. | Procedure: Buccal Administration of nicotine<br>* Oral pouch 0.3 g, single dose. One pouch administered over 30 minutes.<br>* Other names: PREP;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-vivo extraction of cadmium | Extracted amount = mean of 10 unused sachets - residual amount | 30 minutes' use | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| in-vivo extraction of tobacco specific nitrosamines (TSNAs) | Extracted amount = mean of 10 unused sachets - residual amount in used sachet | 30 minutes' use | 
| In-vivo extraction of lead | Extracted amount = mean of 10 unused sachets - residual amount in one used sachet | 30 minutes' use | 
| In-vivo extraction of nicotine | Extracted amount = mean of 10 unused sachets - residual amount in one used sachet | 30 minutes' use | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
smokeless tobacco, Nicotine, Cadmium, lead, Tobacco Specific Nitrosamines