xml: <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/NCT06019910</url>
    </required_header>
    <id_info>
      <org_study_id>snus2023</org_study_id>
      <nct_id>NCT06019910</nct_id>
    </id_info>
    <brief_title>Snus and Home Blood Pressure</brief_title>
    <official_title>The Effects of Snus on Home Blood Pressure and Metabolism</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital, Linkoeping</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Hospital, Linkoeping</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Snus is a type of snuff that is administered sublabially, that has not been studied regarding&#xD;
        the effects on home blood pressure and metabolism on a longer time frame. The primary aim of&#xD;
        this study is to evaluate the effect of snus on home BP within weeks to months in former snus&#xD;
        users who continue to not use snus or relapse in daily snus use, respectively. The secondary&#xD;
        aim is to evaluate the effects on metabolic measurements. The hypothesis is that BP will&#xD;
        increase amongst the participants that resume snus intake.&#xD;
  &#xD;
        28 healthy volunteers with a pre-existing daily use of snus will be recruited and followed&#xD;
        during snus cessation. Home blood pressure, lipid and metabolic markers will be measured&#xD;
        before and after snus cessation, as well as after snus relapse if such a relapse occurs.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Both elevated blood pressure (BP) and cigarette smoking increases the risk of cardiovascular&#xD;
        disease. Nicotine, through effects on the nervous system and catecholamine release, increases&#xD;
        BP and heart rate, peaking 5-10 minutes after exposure, after which tolerance to nicotine&#xD;
        reduces its hemodynamic effects. Smoking also increases energy expenditure, but studies on&#xD;
        smoking and long-term metabolism have shown conflicting results.&#xD;
  &#xD;
        Snus is a type of snuff that is administered sublabially, that has not been studied regarding&#xD;
        the effects on home blood pressure and metabolism on a longer time frame. The primary aim of&#xD;
        this study is to evaluate the effect of snus on home BP within weeks to months in former snus&#xD;
        users who continue to not use snus or relapse in daily snus use, respectively. The secondary&#xD;
        aim is to evaluate the effects on metabolic measurements. The hypothesis is that BP will&#xD;
        increase amongst the participants that resume snus intake.&#xD;
  &#xD;
        28 healthy volunteers with a pre-existing daily use of snus will be recruited and followed&#xD;
        during snus cessation for 3 months. Home blood pressure, lipid and metabolic markers will be&#xD;
        measured before and after snus cessation. Furthermore, for participants which relapse in snus&#xD;
        use, the same measurements will be followed for an additional 3 months. Home blood pressure&#xD;
        will be measured daily, and participants will also report the amount of snus use each day. At&#xD;
        week 0, 4 and 12 of snus cessation and snus relapse, the following measurements will also be&#xD;
        made: body weight as well as plasma glucose, blood glycated hemoglobin (HbA1c), serum&#xD;
        insulin, plasma lipid profile (total cholesterol, low-density lipoprotein, high-density&#xD;
        lipoprotein, and triglycerides), plasma hsCRP, plasma creatinine, plasma sodium, and plasma&#xD;
        potassium.&#xD;
  &#xD;
        As reimbursement, participants will receive (at least) 1000 Swedish krona (Approx 94 US&#xD;
        dollar) for the drawing of blood tests. All participants will give written, informed consent&#xD;
        prior to participation. The study will comply with the declaration of Helsinki and be&#xD;
        approved by the Swedish Ethical Review Authority. Prior to commencement, the study will be&#xD;
        registered at ClinicalTrials.gov.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 18, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">June 30, 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_model_description>At baseline, all participants use snus, and will be asked to quit their usage. They will then be followed for up to 12 weeks. If and when they relapse in snus use, another 12 weeks will commence, during which the same measurements will repeated but for a second period of up to 12 weeks.</intervention_model_description>
      <primary_purpose>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Home blood pressure during snus cessation</measure>
      <time_frame>4-12 weeks</time_frame>
      <description>Change in home blood pressure from baseline until week 4 and week 12 respectively</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Home blood pressure during snus relapse</measure>
      <time_frame>4-12 weeks</time_frame>
      <description>Change in home blood pressure from week 0 of snus relapse until week 4 and week 12 respectively</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Body weight during snus cessation</measure>
      <time_frame>4-12 weeks</time_frame>
      <description>Change in body weight from baseline until week 4 and week 12 respectively</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of plasma lipids during snus cessation</measure>
      <time_frame>4-12 weeks</time_frame>
      <description>Change in plasma lipids from baseline until week 4 and week 12 respectively</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of fasting plasma glucose during snus cessation</measure>
      <time_frame>4-12 weeks</time_frame>
      <description>Change in fasting plasma glucose from baseline until week 4 and week 12 respectively</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of fasting plasma insulin during snus cessation</measure>
      <time_frame>4-12 weeks</time_frame>
      <description>Change in fasting plasma insulin from baseline until week 4 and week 12 respectively</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of blood HbA1c during snus cessation</measure>
      <time_frame>4-12 weeks</time_frame>
      <description>Change in blood HbA1c from baseline until week 4 and week 12 respectively</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Body weight during snus relapse</measure>
      <time_frame>4-12 weeks</time_frame>
      <description>Change in body weight from week 0 of snus relapse until week 4 and week 12 respectively</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of plasma lipids during snus relapse</measure>
      <time_frame>4-12 weeks</time_frame>
      <description>Change in plasma lipids from week 0 of snus relapse until week 4 and week 12 respectively</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of fasting plasma glucose during snus relapse</measure>
      <time_frame>4-12 weeks</time_frame>
      <description>Change in fasting plasma glucose from week 0 of snus relapse until week 4 and week 12 respectively</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of fasting plasma insulin during snus relapse</measure>
      <time_frame>4-12 weeks</time_frame>
      <description>Change in fasting plasma insulin from week 0 of snus relapse until week 4 and week 12 respectively</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of blood HbA1c during snus relapse</measure>
      <time_frame>4-12 weeks</time_frame>
      <description>Change in blood HbA1c from week 0 of snus relapse until week 4 and week 12 respectively</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">28</enrollment>
    <condition>Blood Pressure</condition>
    <condition>Dyslipidemias</condition>
    <condition>Dysglycemia</condition>
    <condition>Obesity</condition>
    <arm_group>
      <arm_group_label>Snus with or without tobacco</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Snus cessation followed by potential snus relapse</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Snus with or without tobacco</intervention_name>
      <description>At baseline, participants have used the intervention daily for at least 30 days. They will then cease usage of the intervention abruptly. After 3 weeks, they may continue to abstain from the intervention or relapse at their own discretion.</description>
      <arm_group_label>Snus with or without tobacco</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  daily use (defined as at least once daily for at least 1 month) o snus&#xD;
  &#xD;
            -  the ability to use online questionnaires written and answered in Swedish&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  simultaneous use of any other nicotine or tobacco product (including cigarette&#xD;
               smoking, e-cigarettes, and nicotine replacement therapy)&#xD;
  &#xD;
            -  drug use (including cannabis)&#xD;
  &#xD;
            -  alcohol dependence&#xD;
  &#xD;
            -  known cardiovascular disease (including hypertension, previous myocardial infarction,&#xD;
               stroke, peripheral arterial disease, or angina pectoris), kidney disease, hormonal&#xD;
               disease (including diabetes mellitus) or eating disorder&#xD;
  &#xD;
            -  current or planned pregnancy.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>50 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Fredrik H Nyström, PhD, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Linkoeping University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Peder af Geijerstam, MD</last_name>
      <phone>+460739597426</phone>
      <email>peder.af.geijerstam@liu.se</email>
    </overall_contact>
    <reference>
      <citation>Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I; Authors/Task Force Members:. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018 Oct;36(10):1953-2041. doi: 10.1097/HJH.0000000000001940. Erratum In: J Hypertens. 2019 Jan;37(1):226.</citation>
      <PMID>30234752</PMID>
    </reference>
    <reference>
      <citation>Benowitz NL, Pipe A, West R, Hays JT, Tonstad S, McRae T, Lawrence D, St Aubin L, Anthenelli RM. Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers: A Randomized Clinical Trial. JAMA Intern Med. 2018 May 1;178(5):622-631. doi: 10.1001/jamainternmed.2018.0397.</citation>
      <PMID>29630702</PMID>
    </reference>
    <reference>
      <citation>Middlekauff HR, Park J, Moheimani RS. Adverse effects of cigarette and noncigarette smoke exposure on the autonomic nervous system: mechanisms and implications for cardiovascular risk. J Am Coll Cardiol. 2014 Oct 21;64(16):1740-50. doi: 10.1016/j.jacc.2014.06.1201.</citation>
      <PMID>25323263</PMID>
    </reference>
    <reference>
      <citation>Martinez-Morata I, Sanchez TR, Shimbo D, Navas-Acien A. Electronic Cigarette Use and Blood Pressure Endpoints: a Systematic Review. Curr Hypertens Rep. 2020 Nov 23;23(1):2. doi: 10.1007/s11906-020-01119-0.</citation>
      <PMID>33230755</PMID>
    </reference>
    <reference>
      <citation>Audrain-McGovern J, Benowitz NL. Cigarette smoking, nicotine, and body weight. Clin Pharmacol Ther. 2011 Jul;90(1):164-8. doi: 10.1038/clpt.2011.105. Epub 2011 Jun 1. No abstract available.</citation>
      <PMID>21633341</PMID>
    </reference>
    <reference>
      <citation>Chiolero A, Faeh D, Paccaud F, Cornuz J. Consequences of smoking for body weight, body fat distribution, and insulin resistance. Am J Clin Nutr. 2008 Apr;87(4):801-9. doi: 10.1093/ajcn/87.4.801.</citation>
      <PMID>18400700</PMID>
    </reference>
    <reference>
      <citation>Hofstetter A, Schutz Y, Jequier E, Wahren J. Increased 24-hour energy expenditure in cigarette smokers. N Engl J Med. 1986 Jan 9;314(2):79-82. doi: 10.1056/NEJM198601093140204.</citation>
      <PMID>3941694</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 30, 2023</study_first_submitted>
    <study_first_submitted_qc>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 31, 2023</study_first_posted>
    <last_update_submitted>September 2, 2023</last_update_submitted>
    <last_update_submitted_qc>September 2, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University Hospital, Linkoeping</investigator_affiliation>
      <investigator_full_name>Fredrik H Nystrom</investigator_full_name>
      <investigator_title>Professor of internal medicine and endocrinology</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Dyslipidemias</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06019910
  org study id: snus2023
  nct id: NCT06019910
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Snus is a type of snuff that is administered sublabially, that has not been studied regarding
        the effects on home blood pressure and metabolism on a longer time frame. The primary aim of
        this study is to evaluate the effect of snus on home BP within weeks to months in former snus
        users who continue to not use snus or relapse in daily snus use, respectively. The secondary
        aim is to evaluate the effects on metabolic measurements. The hypothesis is that BP will
        increase amongst the participants that resume snus intake.
  
        28 healthy volunteers with a pre-existing daily use of snus will be recruited and followed
        during snus cessation. Home blood pressure, lipid and metabolic markers will be measured
        before and after snus cessation, as well as after snus relapse if such a relapse occurs.
  Both elevated blood pressure (BP) and cigarette smoking increases the risk of cardiovascular
        disease. Nicotine, through effects on the nervous system and catecholamine release, increases
        BP and heart rate, peaking 5-10 minutes after exposure, after which tolerance to nicotine
        reduces its hemodynamic effects. Smoking also increases energy expenditure, but studies on
        smoking and long-term metabolism have shown conflicting results.
  
        Snus is a type of snuff that is administered sublabially, that has not been studied regarding
        the effects on home blood pressure and metabolism on a longer time frame. The primary aim of
        this study is to evaluate the effect of snus on home BP within weeks to months in former snus
        users who continue to not use snus or relapse in daily snus use, respectively. The secondary
        aim is to evaluate the effects on metabolic measurements. The hypothesis is that BP will
        increase amongst the participants that resume snus intake.
  
        28 healthy volunteers with a pre-existing daily use of snus will be recruited and followed
        during snus cessation for 3 months. Home blood pressure, lipid and metabolic markers will be
        measured before and after snus cessation. Furthermore, for participants which relapse in snus
        use, the same measurements will be followed for an additional 3 months. Home blood pressure
        will be measured daily, and participants will also report the amount of snus use each day. At
        week 0, 4 and 12 of snus cessation and snus relapse, the following measurements will also be
        made: body weight as well as plasma glucose, blood glycated hemoglobin (HbA1c), serum
        insulin, plasma lipid profile (total cholesterol, low-density lipoprotein, high-density
        lipoprotein, and triglycerides), plasma hsCRP, plasma creatinine, plasma sodium, and plasma
        potassium.
  
        As reimbursement, participants will receive (at least) 1000 Swedish krona (Approx 94 US
        dollar) for the drawing of blood tests. All participants will give written, informed consent
        prior to participation. The study will comply with the declaration of Helsinki and be
        approved by the Swedish Ethical Review Authority. Prior to commencement, the study will be
        registered at ClinicalTrials.gov.
  allocation: N/A
  intervention model: Sequential Assignment
  intervention model description: At baseline, all participants use snus, and will be asked to quit their usage. They will then be followed for up to 12 weeks. If and when they relapse in snus use, another 12 weeks will commence, during which the same measurements will repeated but for a second period of up to 12 weeks.
  primary purpose: Prevention
  masking: None (Open Label)
  measure: Home blood pressure during snus cessation
  time frame: 4-12 weeks
  description: Change in home blood pressure from baseline until week 4 and week 12 respectively
  measure: Home blood pressure during snus relapse
  time frame: 4-12 weeks
  description: Change in home blood pressure from week 0 of snus relapse until week 4 and week 12 respectively
  measure: Body weight during snus cessation
  time frame: 4-12 weeks
  description: Change in body weight from baseline until week 4 and week 12 respectively
  measure: Concentration of plasma lipids during snus cessation
  time frame: 4-12 weeks
  description: Change in plasma lipids from baseline until week 4 and week 12 respectively
  measure: Concentration of fasting plasma glucose during snus cessation
  time frame: 4-12 weeks
  description: Change in fasting plasma glucose from baseline until week 4 and week 12 respectively
  measure: Concentration of fasting plasma insulin during snus cessation
  time frame: 4-12 weeks
  description: Change in fasting plasma insulin from baseline until week 4 and week 12 respectively
  measure: Concentration of blood HbA1c during snus cessation
  time frame: 4-12 weeks
  description: Change in blood HbA1c from baseline until week 4 and week 12 respectively
  measure: Body weight during snus relapse
  time frame: 4-12 weeks
  description: Change in body weight from week 0 of snus relapse until week 4 and week 12 respectively
  measure: Concentration of plasma lipids during snus relapse
  time frame: 4-12 weeks
  description: Change in plasma lipids from week 0 of snus relapse until week 4 and week 12 respectively
  measure: Concentration of fasting plasma glucose during snus relapse
  time frame: 4-12 weeks
  description: Change in fasting plasma glucose from week 0 of snus relapse until week 4 and week 12 respectively
  measure: Concentration of fasting plasma insulin during snus relapse
  time frame: 4-12 weeks
  description: Change in fasting plasma insulin from week 0 of snus relapse until week 4 and week 12 respectively
  measure: Concentration of blood HbA1c during snus relapse
  time frame: 4-12 weeks
  description: Change in blood HbA1c from week 0 of snus relapse until week 4 and week 12 respectively
  arm group label: Snus with or without tobacco
  arm group type: Experimental
  description: Snus cessation followed by potential snus relapse
  intervention type: Other
  intervention name: Snus with or without tobacco
  description: At baseline, participants have used the intervention daily for at least 30 days. They will then cease usage of the intervention abruptly. After 3 weeks, they may continue to abstain from the intervention or relapse at their own discretion.
  arm group label: Snus with or without tobacco
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 50 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Fredrik H Nyström, PhD, MD
  role: Principal Investigator
  affiliation: Linkoeping University
  last name: Peder af Geijerstam, MD
  phone: +460739597426
  email: peder.af.geijerstam@liu.se
  citation: Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I; Authors/Task Force Members:. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018 Oct;36(10):1953-2041. doi: 10.1097/HJH.0000000000001940. Erratum In: J Hypertens. 2019 Jan;37(1):226.
  PMID: 30234752
  citation: Benowitz NL, Pipe A, West R, Hays JT, Tonstad S, McRae T, Lawrence D, St Aubin L, Anthenelli RM. Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers: A Randomized Clinical Trial. JAMA Intern Med. 2018 May 1;178(5):622-631. doi: 10.1001/jamainternmed.2018.0397.
  PMID: 29630702
  citation: Middlekauff HR, Park J, Moheimani RS. Adverse effects of cigarette and noncigarette smoke exposure on the autonomic nervous system: mechanisms and implications for cardiovascular risk. J Am Coll Cardiol. 2014 Oct 21;64(16):1740-50. doi: 10.1016/j.jacc.2014.06.1201.
  PMID: 25323263
  citation: Martinez-Morata I, Sanchez TR, Shimbo D, Navas-Acien A. Electronic Cigarette Use and Blood Pressure Endpoints: a Systematic Review. Curr Hypertens Rep. 2020 Nov 23;23(1):2. doi: 10.1007/s11906-020-01119-0.
  PMID: 33230755
  citation: Audrain-McGovern J, Benowitz NL. Cigarette smoking, nicotine, and body weight. Clin Pharmacol Ther. 2011 Jul;90(1):164-8. doi: 10.1038/clpt.2011.105. Epub 2011 Jun 1. No abstract available.
  PMID: 21633341
  citation: Chiolero A, Faeh D, Paccaud F, Cornuz J. Consequences of smoking for body weight, body fat distribution, and insulin resistance. Am J Clin Nutr. 2008 Apr;87(4):801-9. doi: 10.1093/ajcn/87.4.801.
  PMID: 18400700
  citation: Hofstetter A, Schutz Y, Jequier E, Wahren J. Increased 24-hour energy expenditure in cigarette smokers. N Engl J Med. 1986 Jan 9;314(2):79-82. doi: 10.1056/NEJM198601093140204.
  PMID: 3941694
  responsible party type: Principal Investigator
  investigator affiliation: University Hospital, Linkoeping
  investigator full name: Fredrik H Nystrom
  investigator title: Professor of internal medicine and endocrinology
  mesh term: Dyslipidemias