Sympathovagal Balance in Smoking Cessation

Study Overview
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Brief Summary
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This study has the following primary aim: - the main objective of this study is to investigate the effects of smoking cessation during quit attempts on sympathovagal balance. These effects will be observed in smokers quitting smoking with pharmacological support or without. Secondary aims of this study are also: the definition of MSNA in smokers and non-smokers the investigation of other parameters concerning the autonomic nervous system, like baroreflex-sensitivity, heart rate-variability before and during the quit attempt. the definition of withdrawal symptoms and craving before, during and after the quit attempt. the investigation of effects of smoking cues on craving and sympathovagal balance the investigation of relapse rates after smoking cessation in correlation with the parameters mentioned above.

Official Title
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Alterations in the Autonomic Nervous System During Smoking Quit Attempts- Possible Effects of Pharmacological Interventions

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: Varenicline
* Drug: Placebo
* Drug: Nicorette TX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and Women at the age of 25 to 60 years. Group A-D: Smokers willing to quit smoking and a FTNA-result >5. Group E: Never-smokers. Signed consent after information. Exclusion Criteria: formerly known hypersensitivity against one of the used pharmacological interventions or structurally similar drugs or against one of the ingredients. participation in another study during this study or within 4 weeks prior to this study. Addiction or other circumstances that prevent the patient from estimating the study and the consequences. Pregnancy and breast-feeding women with childbearing potential, except women that fulfill the following criteria: post menopause postoperative (6 weeks after both-sides ovariectomy with or without hysterectomy) regular and correct use of prevention methods (error-rate <1% a year), e.g. implants, depot injections, oral contraceptives, IUP) sexual abstinence signs that predict a possible non-compliance of the patient exclusion because of nicorette tx: psoriasis, dermatitis, urticaria exclusion because of varenicline creatinine-clearance < 30ml/min epilepsy psychiatric diseases (schizophrenia, bipolar disorders, depression). Exclusion because of methods Diseases that increase the sympathetic level (Heart insufficiency, high blood pressure (arteria /pulmonary), obstructive sleeping apnoea, COPD) cardiac rhythm disturbances myocardial infarction within the last 8 weeks polyneuropathy diseases that come along with damages of peripheral nerves severe or life-threatening diseases (e.g. cancer with life-expectancy < 5 years, terminal kidney-insufficiency) treatment with antihypertensive drugs or sympathomimetic substances (e.g.theophyllin) or smoking cessation medication (NRT, Varenicline) Other reasons, that make a patient not suitable for the study (estimation of primary investigator)

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: varenicline placebo<br> | Drug: Placebo<br>* 1-2 tablets per day, oral use<br>|
| Active Comparator: varenicline<br> | Drug: Varenicline<br>* 0.5-2 mg per day, oral use<br>|
| Active Comparator: Nicorette TX<br> | Drug: Nicorette TX<br>* 10-15 mg per day, transdermal use (patches)<br>|
| Active Comparator: Nicorette TX optional<br> | Drug: Nicorette TX<br>* 10-15 mg per day, transdermal use (patches)<br>|
| No Intervention: control group smokers<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of muscular sympathic nervous activity (MSNA) in bursts / 100 heart beats before and while smoking cessation. | Patients present 7 weeks before their personal smoking-stop-day and participate in the study until week 26 after their personal smoking-stop-day. During that time, MSNA is recorded. | 33 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the basal sympathetic nerve activity in smokers compared to never-smokers | first MSNA is carried out 4 weeks before smoking-stop-day (respectively 6 weeks for group D). second and last MSNA is carried out two days after smoking-stop-day (respectively 2 weeks before smoking-stop-day for group D) | 33 weeks | 
| Assessment of craving and withdrawal symptoms during smoking cessation | withdrawal symptoms data is collected by phone calls 3,2,1 days before smoking-stop-day, the day itself and 1 day and 11 (12 for group C and D) weeks after smoking-stop-day. Also the withdrawal symptoms date is collected during each personal examination (means - Pre-Examination, Baseline, Follow I to III). The data will be collected by reliable questionnaires | 33 weeks | 
| Assessment of smoking cues on craving and sympathovagal balance | smoking cues will be presented on the first follow-up-measurement to members of group A-D. | 33 weeks | 
| Assessment of smoking relapse rate | All relapses will be registered to correlate them with the obtained parameters (baroreflex-sensitivity, heartrate-variabilty, MSNA, questionnaires) | 33 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smoking cessation, varenicline, sympathovagal balance, quit attempts, MSNA