Efficacy of 2 Probiotics During Nicotine Replacement Therapy on Withdrawal Symptoms Associated With Smoking Cessation

Study Overview
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Brief Summary
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Quitting smoking is a big decision, a decision to achieve better health. Trying to quit smoking can be stressful. The prospect of dealing with withdrawal symptoms, fear or failure to change the routine, can also be sources of stress. Withdrawal from nicotine is characterized by symptoms that include anxiety, irritability, hunger and cravings for more tobacco. Nicotine creates a dependency so that the body develops a need for a certain level of nicotine at all times. Unless that level is maintained symptoms of withdrawal appear. For tobacco users trying to quit, symptoms of withdrawal from nicotine are unpleasant and stressful, but they are temporary. Research has demonstrated the relative effectiveness of pharmacotherapy treatments in smoking cessation but no studies have examined the effects of the probiotics on the withdrawal symptoms associated with the tobacco cessation during nicotine replacement therapy (NRT). The purpose of this study is to assess the effectiveness of two probiotic products during NRT for managing withdrawal symptoms associated with smoking cessation.

Official Title
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A Double-blind Randomized Placebo-controlled Trial Assessing the Effectiveness of Two Probiotic Products During Nicotine Replacement Therapy for Managing Withdrawal Symptoms Associated With Smoking Cessation

Conditions
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Smoking Cessation

Intervention / Treatment
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* Dietary Supplement: Probiotic L008-1
* Dietary Supplement: Probiotic L008-2
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18-65 years Moderate or heavy smokers as defined by: a score at the Fargerström Test for Nicotine Dependence ≥ 5, and who smoke more than 10 cigarettes per day. Participants willing to stop smoking, corresponding to a score of 6 or 7 to the Motivation To Stop Scale. The MTSS is a one-item questionnaire with 7 possible choices, from 1 (lowest level of motivation to stop smoking) to level 7 (highest level of motivation to stop smoking). Participants need to be able to understand and consent to, and willing to comply with study procedures. Willingness to discontinue consumption of probiotic supplements and food containing added probiotics or and/or prebiotics (e.g. yoghourts, with live, active cultures or supplements). Exclusion Criteria: Positive pregnancy test in women of child-bearing potential Pregnant or breast-feeding or planning on becoming pregnant. Women of child-bearing potential not using effective contraception, wich include : Hormonal contraceptives including combined oral contraceptives, hormone birth control patch, vaginal contraceptive ring, injectable contraceptives, or hormonal implants; Intrauterine devices (IUD) or Intrauterine system (IUS); Tubal ligation; Vasectomy of partner; Double barrier method (use of physical barrier by both partners, e.g. male condom and diaphragm, male condom and cervical cap) Use of another investigational product within 3 months of the screening visit. Currently being treated for any known illnesses or conditions that may impact perceived health such as HIV/AIDS, immune modulating diseases (autoimmune, hepatitis, cancer, etc.), diabetes, kidney or liver disease, gastrointestinal diseases (e.g. gastric ulcers, Crohn's, ulcerative colitis, etc.) Suffered or suffering from heart attack, angina, heart arrhythmias, stroke, heart disease, thyroid problems, and diabetes requiring insulin. Participants with eczema, psoriasis, dermatitis or urticaria. Participants with soy or milk allergy. Participants with allergies to adhesive tape or bandages.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic L008-1<br>Encapsuled combinaison of 2 probiotics | Dietary Supplement: Probiotic L008-1<br>* Dosing regimen of 2 capsules daily, once per day, for 14 weeks<br>|
| Experimental: Probiotic L008-2<br>Encapsuled combinaison of 2 probiotics | Dietary Supplement: Probiotic L008-2<br>* Dosing regimen of 2 capsules daily, once per day, for 14 weeks<br>|
| Placebo Comparator: Placebo<br>Encapsuled non active ingredients | Other: Placebo<br>* Dosing regimen of 2 capsules daily, once per day, for 14 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of the withdrawal symptoms assessed by the Mood and Physical Symptoms Scale (MPSS) | The MPSS(M) score, corresponding to the sum of the 7 items of the MPSS mood subscale, will be compared between groups, daily between week 2 and 4 (first 2 weeks of tobacco abstinence) and week 12 and 14 (first 2 weeks after the end of NRT), and weekly for the other weeks. For weekly comparisons, an average of daily scores will be done for the respective weeks. The score will also be compared in time within groups, using the baseline ratings as covariates | MPSS will be self-administered daily during 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of anxiety and depression assessed by the HADS questionnaire |  | measured 6 times up to 16 weeks | 
| Evolution of nicotine addiction assessed by the Fargerström Test for Nicotine Dependence |  | measured 3 times up to 16 weeks | 
| Difference in tobacco abstinence between arms, determined by levels of exhaled CO and salivary cotinine dosage |  | measured 6 times up to 16 weeks | 
| Evolution of body weight |  | measured 6 times up to 16 weeks | 
| Evolution of food cravings | Assessed by the Food Cravings Self-Questionnaire | self-reported, weekly, up to 16 weeks | 
| Tolerance of the probiotics against placebo | Assessed by the reporting and the comparison of the Adverse events occurred in the different arms | up to 16 weeks | 
| Effect of probiotics and smoking cessation on daily bowel movement frequency and consistency, assessed by the Bristol Stool Scale |  | Self-reported, daily during 16 weeks | 
| Changes in the microbiome composition of participants in the probiotic groups compared to placebo | Assessed by the analyse of the stool samples collected | measured 2 times up to 16 weeks | 
| Recovery of the probiotic strains in the stools | Assessed by the change in the probiotic strains concentration in the stools samples collected in all three arms. | measrured 2 times up to 16 weeks | 
| Evolution of nicotine addiction assessed by a visual analog scale |  | measured 6 times up to 16 weeks | 
| Comparison of MPSS(Craving or C), MPSS(Physical symptoms or P), and MPSS total scores (corresponding to the sum of MPSS(M), MPSS(C) and MPSS(M) scores) | daily comparison between week 2 and 4 (first 2 weeks of tobacco abstinence) and week 12 and 14 (first 2 weeks after the end of NRT), and weekly for the other weeks. The scores will be also compared in time within groups, using the baseline ratings as covariates. For weekly comparisons, an average of daily scores will be done for the respective weeks | MPSS will be self-administered daily during 16 weeks | 
| Correlation between CO levels in exhaled air and salivary cotinine levels |  | measured 6 times up to 16 weeks |