<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02991781</url>
  </required_header>
  <id_info>
    <org_study_id>SEP-210254111</org_study_id>
    <nct_id>NCT02991781</nct_id>
  </id_info>
  <brief_title>Combined Bio- and Neuro- Feedback vs. Varenicline Use for Smoking Cessation</brief_title>
  <official_title>Multidisciplinary Tools for Improving the Efficacy of Public Prevention Measures Against Smoking</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aristotle University Of Thessaloniki</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AAI Scientific Cultural Services Ltd (AAISCS)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>NATIONAL ASSOCIATION OF GENERAL PRACTITIONERS IN BULGARIA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Aristotle University Of Thessaloniki</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will develop and experimentally test the efficiency of a neurofeedback training&#xD;
      protocol vs. varenicline use for smoking cessation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will develop and experimentally test the efficiency of a neurofeedback(NF)&#xD;
      training protocol for smoking cessation. As non-pharmacological, non-invasive and painless&#xD;
      brainwave technique, NF contributes to teach individuals how they can take the control of&#xD;
      their mind through operant conditioning. NF regulates brain function in natural way. Studies&#xD;
      have reported an 80% rate of reducing or eliminating the need for traditional medication14.&#xD;
      Therefore, other nicotine substitutes (such as varenicline) which may carry their own&#xD;
      toxicity risk factor may become redundant. The protocol will include 5 bio- and 25&#xD;
      Neuro-feedback sessions, lasting approximately 36 months.&#xD;
&#xD;
      The electrophysiological evaluation of the efficacy of the intervention will include EEG&#xD;
      resting state and a multifeature Mismatch Negativity (MMN) evoked response measurements&#xD;
      before and after the participation of human volunteers. These data will be analyzed in terms&#xD;
      of cortical activation patterns and cortical connectivity. Questionnaires will be used to&#xD;
      collect behavioral and psychometric data regarding smoking related behaviors. Additionally, a&#xD;
      clinical evaluation including spirometry, exhaled carbon monoxide, total antioxidant&#xD;
      capacity, vitamine E, and cotinine will be conducted. The data will be collected prior,&#xD;
      during, after the completion of the study and after a one-year follow up.&#xD;
&#xD;
      The Neurofeedback intervention will be compared to a different group of participants that&#xD;
      will follow an intervention based on varenicline use for approximately 3 months. The&#xD;
      electrophysiological evaluation of the efficacy of the intervention will include EEG resting&#xD;
      state and a sleep polysomnography measurement. Questionnaires and clinical evaluation include&#xD;
      the same measurements as the neurofeedback intervention but only in 3 time points: prior,&#xD;
      during, after the completion of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2017</start_date>
  <completion_date type="Actual">June 2019</completion_date>
  <primary_completion_date type="Actual">June 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Neurofeedback vs. Varenicline efficacy for smoking cessation</measure>
    <time_frame>2 years</time_frame>
    <description>The outcome measure is the effect size of each intervention measured in standardized percentage of participants that give up smoking.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effectiveness in changing quality of life as measured by EuroQL-5D</measure>
    <time_frame>2 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>General health</measure>
    <time_frame>2 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depression</measure>
    <time_frame>2 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anxiety</measure>
    <time_frame>2 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuroplastic effects of combined bio- and neuro- feedback training in the resting state cortical activity</measure>
    <time_frame>2 years</time_frame>
    <description>The outcome measure is the change from baseline in the activation of the resting state cortical network after the completion of the intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuroplastic effects of combined bio- and neuro- feedback training in the mismatch negativity response</measure>
    <time_frame>2 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep quality during varenicline use</measure>
    <time_frame>2 years</time_frame>
    <description>The outcome measure is the change from baseline in the scoring in psychometric tests evaluating sleep quality.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">106</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease (COPD)</condition>
  <condition>Asthma</condition>
  <condition>Smoking</condition>
  <arm_group>
    <arm_group_label>COPD Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>C.O.P.D. patients: Presence of a post-bronchodilator forced expiratory volume at one second (FEV1) / forced vital capacity (FVC) &lt; 0.70 with symptoms as dyspnea, chronic cough, chronic sputum production&#xD;
Biofeedback and Neurofeedback Training&#xD;
Varenicline use for smoking cessation&#xD;
Passive Control</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Asthma Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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 &gt;12% following b2 agonist inhalation) or evidence of bronchial hyperresponsiveness by metacholine provocation test (demonstrated by provocative concentration causing a 20% fall (PC20) &lt;8 mg or mannitol provocation test (with FEV1 decrease of 15%)&#xD;
Biofeedback and Neurofeedback Training&#xD;
Varenicline use for smoking cessation&#xD;
Passive Control</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Smokers</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Smokers will consist of a group of patients that are under the age of 35, unemployed and healthy according to a standard clinical evaluation.&#xD;
Biofeedback and Neurofeedback Training&#xD;
Varenicline use for smoking cessation&#xD;
Sham Neurofeedback&#xD;
Passive Control</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Biofeedback and Neurofeedback Training</intervention_name>
    <description>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.</description>
    <arm_group_label>Asthma Patients</arm_group_label>
    <arm_group_label>COPD Patients</arm_group_label>
    <arm_group_label>Smokers</arm_group_label>
    <other_name>Neurofeedback</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Varenicline use for smoking cessation</intervention_name>
    <description>The protocol will consist 1 mg varenicline use twice daily following a 1-week titration for 3 months.</description>
    <arm_group_label>Asthma Patients</arm_group_label>
    <arm_group_label>COPD Patients</arm_group_label>
    <arm_group_label>Smokers</arm_group_label>
    <other_name>Varenicline</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sham Neurofeedback</intervention_name>
    <description>Subjects will receive equal sessions of sham neurofeedback, and thus serve as a control group for the analysis and design of the study.</description>
    <arm_group_label>Smokers</arm_group_label>
    <other_name>Active Control</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Passive Control</intervention_name>
    <description>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.</description>
    <arm_group_label>Asthma Patients</arm_group_label>
    <arm_group_label>COPD Patients</arm_group_label>
    <arm_group_label>Smokers</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Being continuous tobacco smokers (&gt;10 cigarettes per day) for at least 6 months&#xD;
&#xD;
          -  Being unemployed for at least 3 months&#xD;
&#xD;
          -  Being diagnosed with Asthma&#xD;
&#xD;
          -  Being diagnosed with C.O.P.D.&#xD;
&#xD;
          -  Age &lt; 35, for the group of Young Unemployed&#xD;
&#xD;
          -  Age &gt;35 years, for the groups of Asthma and C.O.P.D. patients&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosed neurological, mental or psychiatric illness&#xD;
&#xD;
          -  Drug-resistance epilepsy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Panos Bamidis, Ass. Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical School, Aristotle University of Thessaloniki</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Association of General Practitioners in Bulgaria</name>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AAI Scientific Cultural Services Ltd (AAISCS)</name>
      <address>
        <city>Nicosia</city>
        <zip>1065</zip>
        <country>Cyprus</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laboratory of Medical Physics, AUTH</name>
      <address>
        <city>Thessaloniki</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Cyprus</country>
    <country>Greece</country>
  </location_countries>
  <link>
    <url>http://smokefreebrain.eu/</url>
    <description>SmokeFreeBrain Project web-site</description>
  </link>
  <reference>
    <citation>Bamidis PD, Paraskevopoulos E, Konstantinidis E, Spachos D, Billis A. Multimodal e-Health Services for Smoking Cessation and Public Health: The SmokeFreeBrain Project Approach. Stud Health Technol Inform. 2017;245:5-9.</citation>
    <PMID>29295041</PMID>
  </reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>May 5, 2015</study_first_submitted>
  <study_first_submitted_qc>December 9, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 14, 2016</study_first_posted>
  <last_update_submitted>February 13, 2020</last_update_submitted>
  <last_update_submitted_qc>February 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Aristotle University Of Thessaloniki</investigator_affiliation>
    <investigator_full_name>Panos Bamidis</investigator_full_name>
    <investigator_title>Dr. Panagiotis Bamidis</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Varenicline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual Patient Data (IPD) will be shared after obtaining the consent of the participants. The consent form will inform the participants for this attribute of the data.&#xD;
The repository will be based on popular open source software (CKAN) and it'll be accessible through a portal (endpoint) at the following address:&#xD;
ckan.smokefreebrain.eu CKAN is a powerful data management system that makes data accessible - by providing tools to streamline publishing, sharing, finding and using data. CKAN is aimed at data publishers (national and regional governments, companies and organizations) wanting to make their data open and available.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>Upon completion of the study</ipd_time_frame>
    <ipd_access_criteria>Following communication with the Principal Investigator</ipd_access_criteria>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_id>neurofeedback-auth</doc_id>
      <doc_type>Individual Participant Data Set</doc_type>
      <doc_url>http://ckan.smokefreebrain.eu/</doc_url>
    </study_doc>
  </study_docs>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02991781
org study id: SEP-210254111
nct id: NCT02991781
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
This study will develop and experimentally test the efficiency of a neurofeedback training
      protocol vs. varenicline use for smoking cessation.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Health Services Research
masking: None (Open Label)
measure: Neurofeedback vs. Varenicline efficacy for smoking cessation
time frame: 2 years
description: The outcome measure is the effect size of each intervention measured in standardized percentage of participants that give up smoking.
measure: Effectiveness in changing quality of life as measured by EuroQL-5D
time frame: 2 years
description: 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.
measure: General health
time frame: 2 years
description: 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.
measure: Depression
time frame: 2 years
description: 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.
measure: Anxiety
time frame: 2 years
description: 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.
measure: Neuroplastic effects of combined bio- and neuro- feedback training in the resting state cortical activity
time frame: 2 years
description: The outcome measure is the change from baseline in the activation of the resting state cortical network after the completion of the intervention.
measure: Neuroplastic effects of combined bio- and neuro- feedback training in the mismatch negativity response
time frame: 2 years
description: 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.
measure: Sleep quality during varenicline use
time frame: 2 years
description: The outcome measure is the change from baseline in the scoring in psychometric tests evaluating sleep quality.
arm group label: COPD Patients
arm group type: Experimental
description: 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
arm group label: Asthma Patients
arm group type: Experimental
description: 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
arm group label: Smokers
arm group type: Experimental
description: 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
intervention type: Other
intervention name: Biofeedback and Neurofeedback Training
description: 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.
arm group label: Asthma Patients
arm group label: COPD Patients
arm group label: Smokers
other name: Neurofeedback
intervention type: Drug
intervention name: Varenicline use for smoking cessation
description: The protocol will consist 1 mg varenicline use twice daily following a 1-week titration for 3 months.
arm group label: Asthma Patients
arm group label: COPD Patients
arm group label: Smokers
other name: Varenicline
intervention type: Other
intervention name: Sham Neurofeedback
description: Subjects will receive equal sessions of sham neurofeedback, and thus serve as a control group for the analysis and design of the study.
arm group label: Smokers
other name: Active Control
intervention type: Other
intervention name: Passive Control
description: 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.
arm group label: Asthma Patients
arm group label: COPD Patients
arm group label: Smokers
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Panos Bamidis, Ass. Prof
role: Principal Investigator
affiliation: Medical School, Aristotle University of Thessaloniki
facility: 
facility: 
facility: 
country: Bulgaria
country: Cyprus
country: Greece
url: http://smokefreebrain.eu/
description: SmokeFreeBrain Project web-site
citation: Bamidis PD, Paraskevopoulos E, Konstantinidis E, Spachos D, Billis A. Multimodal e-Health Services for Smoking Cessation and Public Health: The SmokeFreeBrain Project Approach. Stud Health Technol Inform. 2017;245:5-9.
PMID: 29295041
responsible party type: Principal Investigator
investigator affiliation: Aristotle University Of Thessaloniki
investigator full name: Panos Bamidis
investigator title: Dr. Panagiotis Bamidis
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Varenicline
sharing ipd: Yes
ipd description: Individual Patient Data (IPD) will be shared after obtaining the consent of the participants. The consent form will inform the participants for this attribute of the data.
The repository will be based on popular open source software (CKAN) and it'll be accessible through a portal (endpoint) at the following address:
ckan.smokefreebrain.eu CKAN is a powerful data management system that makes data accessible - by providing tools to streamline publishing, sharing, finding and using data. CKAN is aimed at data publishers (national and regional governments, companies and organizations) wanting to make their data open and available.
ipd info type: Study Protocol
ipd time frame: Upon completion of the study
ipd access criteria: Following communication with the Principal Investigator
study doc: 