Combined Bio- and Neuro- Feedback vs. Varenicline Use for Smoking Cessation

Study Overview
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Brief Summary
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This study will develop and experimentally test the efficiency of a neurofeedback training protocol vs. varenicline use for smoking cessation.

Detailed Description
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This study will develop and experimentally test the efficiency of a neurofeedback(NF) training protocol for smoking cessation. As non-pharmacological, non-invasive and painless brainwave technique, NF contributes to teach individuals how they can take the control of their mind through operant conditioning. NF regulates brain function in natural way. Studies have reported an 80% rate of reducing or eliminating the need for traditional medication14. Therefore, other nicotine substitutes (such as varenicline) which may carry their own toxicity risk factor may become redundant. The protocol will include 5 bio- and 25 Neuro-feedback sessions, lasting approximately 36 months. The electrophysiological evaluation of the efficacy of the intervention will include EEG resting state and a multifeature Mismatch Negativity (MMN) evoked response measurements before and after the participation of human volunteers. These data will be analyzed in terms of cortical activation patterns and cortical connectivity. Questionnaires will be used to collect behavioral and psychometric data regarding smoking related behaviors. Additionally, a clinical evaluation including spirometry, exhaled carbon monoxide, total antioxidant capacity, vitamine E, and cotinine will be conducted. The data will be collected prior, during, after the completion of the study and after a one-year follow up. The Neurofeedback intervention will be compared to a different group of participants that will follow an intervention based on varenicline use for approximately 3 months. The electrophysiological evaluation of the efficacy of the intervention will include EEG resting state and a sleep polysomnography measurement. Questionnaires and clinical evaluation include the same measurements as the neurofeedback intervention but only in 3 time points: prior, during, after the completion of the study.

Official Title
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Multidisciplinary Tools for Improving the Efficacy of Public Prevention Measures Against Smoking

Conditions
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Asthma, Chronic Obstructive Pulmonary Disease (COPD), Smoking

Intervention / Treatment
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* Other: Biofeedback and Neurofeedback Training
* Drug: Varenicline use for smoking cessation
* Other: Sham Neurofeedback
* Other: Passive Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Being continuous tobacco smokers (>10 cigarettes per day) for at least 6 months Being unemployed for at least 3 months Being diagnosed with Asthma Being diagnosed with C.O.P.D. Age < 35, for the group of Young Unemployed Age >35 years, for the groups of Asthma and C.O.P.D. patients Exclusion Criteria: Diagnosed neurological, mental or psychiatric illness Drug-resistance epilepsy

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COPD Patients<br>C.O.P.D. patients: Presence of a post-bronchodilator forced expiratory volume at one second (FEV1) / forced vital capacity (FVC) < 0.70 with symptoms as dyspnea, chronic cough, chronic sputum production Biofeedback and Neurofeedback Training Varenicline use for smoking cessation Passive Control | Other: Biofeedback and Neurofeedback Training<br>* The protocol will consist of 5 sessions of skin temperature biofeedback and 20 sessions of a neurofeedback training protocol that will consist of Alpha-Theta ratio up-training. The aim of the training is to reach a crossover state, were initially Alpha activity will increase and then in a deeper state, the Theta activity will take over. This state is associated with a reverie and disidentification with problems, stress or traumatic experiences. Therefore, the subjects will learn how to increase their Theta/Alpha ratio.<br>* Other names: Neurofeedback;Drug: Varenicline use for smoking cessation<br>* The protocol will consist 1 mg varenicline use twice daily following a 1-week titration for 3 months.<br>* Other names: Varenicline;Other: Passive Control<br>* Subjects will not receive any intervention, but they will be measured via a clinical and psychometric evaluation with a time-difference of 3 months. This is equal to the intervention time. Hence, the subjects in this intervention type will serve as a control group for the analysis and design of the study.<br>|
| Experimental: Asthma Patients<br>Asthma patients: Presence of 2 or more of symptoms of airflow obstruction (cough, wheezing, dyspnea). Airflow obstruction at least partially reversible demonstrated by spirometry with FEV1 increased by >12% following b2 agonist inhalation) or evidence of bronchial hyperresponsiveness by metacholine provocation test (demonstrated by provocative concentration causing a 20% fall (PC20) <8 mg or mannitol provocation test (with FEV1 decrease of 15%) Biofeedback and Neurofeedback Training Varenicline use for smoking cessation Passive Control | Other: Biofeedback and Neurofeedback Training<br>* The protocol will consist of 5 sessions of skin temperature biofeedback and 20 sessions of a neurofeedback training protocol that will consist of Alpha-Theta ratio up-training. The aim of the training is to reach a crossover state, were initially Alpha activity will increase and then in a deeper state, the Theta activity will take over. This state is associated with a reverie and disidentification with problems, stress or traumatic experiences. Therefore, the subjects will learn how to increase their Theta/Alpha ratio.<br>* Other names: Neurofeedback;Drug: Varenicline use for smoking cessation<br>* The protocol will consist 1 mg varenicline use twice daily following a 1-week titration for 3 months.<br>* Other names: Varenicline;Other: Passive Control<br>* Subjects will not receive any intervention, but they will be measured via a clinical and psychometric evaluation with a time-difference of 3 months. This is equal to the intervention time. Hence, the subjects in this intervention type will serve as a control group for the analysis and design of the study.<br>|
| Experimental: Smokers<br>Smokers will consist of a group of patients that are under the age of 35, unemployed and healthy according to a standard clinical evaluation. Biofeedback and Neurofeedback Training Varenicline use for smoking cessation Sham Neurofeedback Passive Control | Other: Biofeedback and Neurofeedback Training<br>* The protocol will consist of 5 sessions of skin temperature biofeedback and 20 sessions of a neurofeedback training protocol that will consist of Alpha-Theta ratio up-training. The aim of the training is to reach a crossover state, were initially Alpha activity will increase and then in a deeper state, the Theta activity will take over. This state is associated with a reverie and disidentification with problems, stress or traumatic experiences. Therefore, the subjects will learn how to increase their Theta/Alpha ratio.<br>* Other names: Neurofeedback;Drug: Varenicline use for smoking cessation<br>* The protocol will consist 1 mg varenicline use twice daily following a 1-week titration for 3 months.<br>* Other names: Varenicline;Other: Sham Neurofeedback<br>* Subjects will receive equal sessions of sham neurofeedback, and thus serve as a control group for the analysis and design of the study.<br>* Other names: Active Control;Other: Passive Control<br>* Subjects will not receive any intervention, but they will be measured via a clinical and psychometric evaluation with a time-difference of 3 months. This is equal to the intervention time. Hence, the subjects in this intervention type will serve as a control group for the analysis and design of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurofeedback vs. Varenicline efficacy for smoking cessation | The outcome measure is the effect size of each intervention measured in standardized percentage of participants that give up smoking. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness in changing quality of life as measured by EuroQL-5D | The outcome measure is the change from baseline in the scoring of the a questionnaire evaluating quality of life (EuroQL-5D), after the completion of the intervention. | 2 years | 
| General health | The outcome measure is the change from baseline in the scoring of the General Health Questionnaire which is evaluating general health, after the completion of the intervention. | 2 years | 
| Depression | The outcome measure is the change from baseline in the scoring of the Beck's Depression Inventory, which is evaluating depression, after the completion of the intervention. | 2 years | 
| Anxiety | The outcome measure is the change from baseline in the scoring of the Spielberger's State -Trait Anxiety Inventory , which is evaluating anxiety, after the completion of the intervention. | 2 years | 
| Neuroplastic effects of combined bio- and neuro- feedback training in the resting state cortical activity | The outcome measure is the change from baseline in the activation of the resting state cortical network after the completion of the intervention. | 2 years | 
| Neuroplastic effects of combined bio- and neuro- feedback training in the mismatch negativity response | The outcome measure is the change from baseline in the activation of the Mismatch Negativity response of the auditory cortex after the completion of the intervention. | 2 years | 
| Sleep quality during varenicline use | The outcome measure is the change from baseline in the scoring in psychometric tests evaluating sleep quality. | 2 years |