<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/NCT03253653</url>
  </required_header>
  <id_info>
    <org_study_id>R01DA042471-01</org_study_id>
    <nct_id>NCT03253653</nct_id>
  </id_info>
  <brief_title>Assessing Toxicity of Waterpipe Tobacco Smoking</brief_title>
  <official_title>Assessing Toxicity of Waterpipe Tobacco Smoking in Laboratory and Naturalistic Settings</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>San Diego State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>San Diego State University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Waterpipe smoking is a tobacco use method in which smoke passes through a partially-filled&#xD;
      water jar. Burning charcoal heats the waterpipe tobacco which produces the smoke that the&#xD;
      user inhales. Waterpipe smoking was associated with increased risk for coronary heart and&#xD;
      pulmonary diseases. This Waterpipe Study will inform the FDA on regulating waterpipe tobacco&#xD;
      products and reduce the harm of it use. This study will be conducted at homes of hookah&#xD;
      smokers, in natural settings, aimed to determine the effects of waterpipe smoking practices&#xD;
      on physiological injury markers and biomarkers of toxicity of waterpipe tobacco smoking. The&#xD;
      investigators will employ a repeated measures design. The investigators will recruit a sample&#xD;
      of 50 adult male and female exclusive waterpipe smokers and a control sample of 25 male and&#xD;
      female non-smokers via intercept interviews from San Diego County, California communities.&#xD;
      Waterpipe smokers will smoke one waterpipe tobacco head (10g) of Starbuzz during 3 separate&#xD;
      sessions with a 7-day washout period before each session, as follows: Session 1, Smoking&#xD;
      waterpipe tobacco using 1 quick-light charcoal and room temperature water in the waterpipe&#xD;
      jar, Session 2, Smoking waterpipe tobacco using 1 quick-light charcoal and adding ice cubes&#xD;
      to the water in the waterpipe jar, and Session 3, Smoking waterpipe tobacco without charcoal&#xD;
      using a charcoal-free electrically heated waterpipe head to heat the tobacco, and room&#xD;
      temperature water in the waterpipe jar. The following data will be collected: a) Tobacco Use&#xD;
      History, b) 4-week Tobacco Exposure Diary, c) Waterpipe Use Session Form, d) Carbon monoxide&#xD;
      (CO) exposure: Micro+ Smokerlyzer® CO monitor will be used for exhaled CO pre and 2 minutes&#xD;
      post each smoking session, e) Pulmonary function testing and measuring blood pressure, heart&#xD;
      rate and respiratory rate, and f) 6 first morning urine samples: pre and post the 3 sessions&#xD;
      to measure urinary cotinine, a metabolite of nicotine, 4-(methylnitrosamino)-1-&#xD;
      (3-pyridyl)-1-butanol (NNAL) and NNAL-glucuronides (total NNAL), metabolites of the lung&#xD;
      carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 1-hydroxypyrene (1-HOP), a&#xD;
      metabolite of the genotoxic carcinogen pyrene, and S-phenylmercapturic acid (SPMA), a&#xD;
      metabolite of the human hematotoxicant and leukemogen benzene. The investigators will explore&#xD;
      exposure levels to furan, a liver toxicant and carcinogen, among waterpipe smokers via&#xD;
      measuring its urinary metabolite Furan-BDA-NAL.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Globally, 1 in 3 adults or 1.2 billion people smoke. The World Health Organization (WHO)&#xD;
      estimated that tobacco is responsible for the death of 1 in 10 adults worldwide, about 6&#xD;
      million premature deaths each year. In the United States (U.S.), cigarette smoking is&#xD;
      responsible for more than 480,000 deaths per year, including nearly 42,000 deaths resulting&#xD;
      from secondhand smoke exposure. Tobacco use is the single leading most preventable cause of&#xD;
      disease, disability, and mortality in the U.S. Tobacco research tends to focus on cigarettes;&#xD;
      however, the rise in waterpipe (WP) tobacco use globally warrants studying all aspects of its&#xD;
      toxicity. In 2005, the WHO called for a better understanding of WP tobacco smoking. In 2007,&#xD;
      the American Lung Association labeled WP smoking as an emerging deadly trend. WP tobacco use&#xD;
      was associated with increased risk for Chronic obstructive pulmonary disease (COPD), heart&#xD;
      diseases, lung cancers, oral and esophageal cancers.&#xD;
&#xD;
      COPD is a major public health problem leading to airflow obstruction. In the U.S., tobacco&#xD;
      smoke is a key factor in the development of COPD, which was the third leading cause of death&#xD;
      in the U.S. in 2014. WP smoking decreases respiratory quality of life in adults. Studies&#xD;
      found that pulmonary function following WP smoking was impaired as measured by forced&#xD;
      expiratory volume (FEV1), forced vital capacity (FVC), FEV1/FVC, and Forced Expiratory Flow&#xD;
      (FEF25-75%). Studies investigating acute cardiovascular injury markers due to WP smoking&#xD;
      showed significant increases in heart rate, and in systolic and diastolic blood pressure.&#xD;
&#xD;
      In 2014, the U.S. Food and Drug Administration (FDA) initiated regulation WP tobacco. The FDA&#xD;
      proposed that the manufacturers of WP tobacco disclose to the FDA their products' ingredients&#xD;
      and report harmful and potentially harmful constituents (HPHCs). A review study showed that&#xD;
      exposures to HPHCs are 10-100 times higher in WP tobacco smoke than in cigarette smoke. To&#xD;
      inform the FDA on the regulation of WP tobacco products, and reduce the harm of it use, the&#xD;
      investigators propose a Waterpipe Project in a natural setting to determine the differential&#xD;
      effects of WP smoking practices on physiological injury markers, and biomarkers of toxicants&#xD;
      and carcinogens.&#xD;
&#xD;
      Worldwide, the WP is used in Africa, Asia, China, India, and the Middle East. Adolescents and&#xD;
      young adults in the U.S. are experimenting with WP smoking. The 2014 U.S. National College&#xD;
      Health Assessment II found that nearly one third of U.S. undergraduate college students&#xD;
      (38.2% of men and 31.4% of women), reported ever using WP tobacco, and 11.6% of men and 8.3%&#xD;
      of women reported current use (past 30 days). Among high school students, the 2013 U.S.&#xD;
      National Youth Tobacco Survey showed that 15.1% of boys and 13.5% of girls reported ever WP&#xD;
      use.&#xD;
&#xD;
      The WP (hookah) consists of a head, a body, a hose, and a water jar. The tobacco is placed in&#xD;
      the head and covered with a perforated aluminum foil to allow air-flow. Burning charcoal is&#xD;
      placed on top of the aluminum foil. Upon deep inhalation via the WP hose, suction forces hot&#xD;
      air through the head, heating and combusting the tobacco to produce the smoke that is forced&#xD;
      down the WP body, into and out of the water in the airtight jar, and through the hose into&#xD;
      the smoker's mouth and respiratory system. Smokers inhale charcoal toxicant emissions in&#xD;
      addition to those from the WP tobacco. Charcoal combustion contributes greatly to benzene,&#xD;
      carbon monoxide (CO) and carcinogenic yields. CO is a smoke toxicant that reduces the blood's&#xD;
      ability to transport oxygen to various organs, including the brain, and can cause dizziness,&#xD;
      headache, syncope and nausea.&#xD;
&#xD;
      A charcoal-free electrically heated WP head is commercially available. Users were satisfied&#xD;
      with this device because they did not have to deal with charcoal fire hazardous ambers and&#xD;
      ashes, in addition to enjoying the feeling of reduced harm. WP smokers normally use room&#xD;
      temperature water in the WP jar. However, other liquid media are gaining in popularity.&#xD;
      According to anecdotal evidence, &quot;adding ice cubes in the WP jar has an enjoyable cooling&#xD;
      effect to the inhaled smoke&quot;. Smokers practice adding ice cubes at home, and for an extra&#xD;
      charge hookah lounges provide this option for customers. Toxic chemicals in WP tobacco smoke&#xD;
      include cotinine, a metabolite of the addictive drug nicotine;&#xD;
      4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and NNAL-glucuronides (total NNAL);&#xD;
      metabolites of the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK);&#xD;
      1-hydroxypyrene (1-HOP), a metabolite of the genotoxic carcinogen pyrene; and&#xD;
      S-phenylmercapturic acid (SPMA), a metabolite of the human hematotoxicant and leukemogen&#xD;
      benzene; and Furan-BDA-NAL, a metabolite of the carcinogen furan.&#xD;
&#xD;
      METHODS. will compare exhaled CO, pulmonary functions, blood pressure, heart rate and&#xD;
      respiratory rate, and urinary levels of cotinine, NNAL, SPMA, and 1-HOP in first void WP&#xD;
      smoker urine samples the morning of, and the morning after a WP smoking session across 3&#xD;
      smoking practices. The investigators will recruit a sample of 50 adult male and female&#xD;
      exclusive WP smokers and a control sample of 25 male and female non-smokers. Participants&#xD;
      will be recruited and qualified via random intercept screen interviews from San Diego County,&#xD;
      California communities. Over a 3-week study period, WP smokers will smoke one WP tobacco head&#xD;
      (10g) of Starbuzz during 3 separate sessions with a 7-day washout period before each session&#xD;
      in their home in a natural setting: Week 1-Session 1, WP smokers will smoke using 1&#xD;
      quick-light charcoal and room temperature water in the WP jar, Week 2-Session 2, WP smokers&#xD;
      will smoke using 1 quick-light charcoal but adding ice cubes to the water in the WP jar, Week&#xD;
      3-Session 3, WP smokers will smoke WP tobacco without charcoal using the electric WP head and&#xD;
      room temperature water. The investigators will collect the following forms: a) Tobacco Use&#xD;
      History; b) 3-week Tobacco Use and Exposure Diaries; c) WP Smoking Session Day and Exposure&#xD;
      Form; and will measure d) CO exposure: Micro+ Smokerlyzer® CO monitor will be used for&#xD;
      exhaled CO two minutes pre and post each smoking session; e) Pulmonary function testing and&#xD;
      measuring blood pressure, heart rate and respiratory rate pre and post each smoking session;&#xD;
      and f) 6 first morning urine samples: pre and post the 3 sessions to measure urinary&#xD;
      cotinine, NNAL, 1-HOP, SPMA, and Furan-BDA-NAL. Efforts will be made to recruit equal samples&#xD;
      of males and females. Flexible scheduling for study activities where applicable. Proration of&#xD;
      incentives will apply for completed activities.&#xD;
&#xD;
      The 3-Week Study period: comprised of 3 WP smoking sessions with 7-day wash-out periods&#xD;
&#xD;
      WP Smoking Session 1. Day 1 - Office Visit: The Office Visit is expected to take between 60&#xD;
      and 90 minutes where potential participants will be trained on the study activities. Consent&#xD;
      will be obtained, study forms will be completed, and study related materials such as forms&#xD;
      and urine cups will be provided. Scheduling will be arranged for the 3 WP smoking sessions&#xD;
      and corresponding home visits. Saliva Test: Trained by the PI, the RAs will use NicAlert, an&#xD;
      accurate and valid commercial semi-quantitative instant saliva cotinine test, to validate&#xD;
      non-smoking status, which the investigators used successfully in their previous studies. The&#xD;
      following physiological baseline data will be collected: pulmonary functions, blood pressure,&#xD;
      heart rate and respiratory rate. Days 2 - 6: The RAs will contact participants by phone on&#xD;
      the 4th day to confirm adherence to the 7-wash-out period and diaries, and on the 6th day to&#xD;
      remind participants to collect the first morning urine sample on day 7, and to arrange for a&#xD;
      home visit for the first WP smoking session. Day 7: WP smoking session 1. WP smokers will&#xD;
      provide one first morning urine sample and store it in their refrigerator (freezer section).&#xD;
      WP smokers will smoke WP tobacco (10 grams) as they normally do using charcoal and room&#xD;
      temperature water in the water jar. The RAs will collect expired CO levels 2 minutes before&#xD;
      and 2 minutes after concluding smoking, and will measure pulmonary functions, blood pressure,&#xD;
      heart rate and respiratory rate thereafter. Day 8: Participants will provide a first morning&#xD;
      urine sample. The RAs will pick up the 2 urine samples (frozen in a cooler to transfer them&#xD;
      to the research center laboratory), and arrange for the 2nd WP smoking session home visit,&#xD;
      provide forms, urine cups package for week 2 of the study. WP Smoking Session 2. Days 1&#xD;
      through 7 are similar to session 1 with the exception that the RAs will add one tray of ice&#xD;
      cubes and water in the WP jar. The RAs will arrange for a training session to use the&#xD;
      charcoal-free electrically heated WP head. WP Smoking Session 3. Days 1 through 7 are similar&#xD;
      to session 1 using room temperature water in the WP jar, however using the charcoal-free&#xD;
      electrically heated WP head instead of using charcoal. During the last visit, the day after&#xD;
      the 3rd smoking session, the RAs will interview participants to complete the Illnesses and&#xD;
      Health Care History Form, pick up the final urine samples, and thank the participants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 20, 2017</start_date>
  <completion_date type="Actual">September 25, 2018</completion_date>
  <primary_completion_date type="Actual">September 25, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>The investigators will employ a repeated measures design. A sample of 50 adult male and female exclusive WP smokers and a control sample of 25 male and female non-smokers will be recruited. Over a 3-week study, WP smokers will smoke one WP tobacco head during each of 3 separate WP smoking sessions with a 7-day washout period before each session. Session 1, WP smokers will smoke using 1 quick-light charcoal and room temperature water in the WP jar; Session 2, WP smokers will smoke using 1 quick-light charcoal but adding ice cubes to the water in the WP jar; Session 3, WP smokers will smoke WP tobacco without charcoal using an electric WP head and room temperature water. Physiological effects, carbon monoxide exposure and biomarkers of toxicants and carcinogens related to WP tobacco smoking practices will be compared.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in urinary cotinine from pre to post each of three waterpipe tobacco smoking sessions</measure>
    <time_frame>Two days for each of the three smoking sessions. Smokers will provide two first morning spot urine samples, one urine sample on the morning of the day of the smoking session, and one urine sample on the morning of the following day.</time_frame>
    <description>The investigators will assess change in urinary levels of cotinine in ng/ml and ng/mg creatinine, which is the metabolite of the addictive drug nicotine, post each of three waterpipe tobacco smoking sessions. For each of the three smoking sessions, smokers will provide two first morning spot urine samples, the day of the smoking session and the following morning. The three waterpipe tobacco smoking sessions are as follows: 1) using room temperature water in the waterpipe jar, 2) adding ice cubes to the water in the waterpipe jar, and 3) using a charcoal-free electronic waterpipe head to heat the tobacco instead of charcoal.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in urinary NNAL from pre to post each of three waterpipe tobacco smoking sessions</measure>
    <time_frame>Two days for each of the three smoking sessions. Smokers will provide two first morning spot urine samples, one urine sample on the morning of the day of the smoking session, and one urine sample on the morning of the following day.</time_frame>
    <description>The investigators will assess change in urinary levels of NNAL in pg/ml and ng/mg creatinine, which is the metabolite of NNK, a tobacco specific pulmonary carcinogen, post each of three waterpipe tobacco smoking sessions. For each of the three smoking sessions, smokers will provide two first morning spot urine samples, the day of the smoking session and the following morning. The three waterpipe tobacco smoking sessions are as follows: 1) using room temperature water in the waterpipe jar, 2) adding ice cubes to the water in the waterpipe jar, and 3) using a charcoal-free electronic waterpipe head to heat the tobacco instead of charcoal.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in urinary SPMA from pre to post each of three waterpipe tobacco smoking sessions</measure>
    <time_frame>Two days for each of the three smoking sessions. Smokers will provide two first morning spot urine samples, one urine sample on the morning of the day of the smoking session, and one urine sample on the morning of the following day.</time_frame>
    <description>The investigators will assess change in urinary levels of SPMA in pmol/ml and pmol/mg creatinine, which is the metabolite of benzene, the human hematotoxicant and leukemogen, post each of three waterpipe tobacco smoking sessions. For each of the three smoking sessions, smokers will provide two first morning spot urine samples, the day of the smoking session and the following morning. The three waterpipe tobacco smoking sessions are as follows: 1) using room temperature water in the waterpipe jar, 2) adding ice cubes to the water in the waterpipe jar, and 3) using a charcoal-free electronic waterpipe head to heat the tobacco instead of charcoal.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in urinary 1-HOP from pre to post each of three waterpipe tobacco smoking sessions</measure>
    <time_frame>Two days for each of the three smoking sessions. Smokers will provide two first morning spot urine samples, one urine sample on the morning of the day of the smoking session, and one urine sample on the morning of the following day.</time_frame>
    <description>The investigators will assess change in urinary levels of 1-HOP in pmol/ml and pmol/mg creatinine, which is the metabolite of pyrene, a genotoxic carcinogen, post each of three waterpipe tobacco smoking sessions. For each of the three smoking sessions, smokers will provide two first morning spot urine samples, the day of the smoking session and the following morning. The three waterpipe tobacco smoking sessions are as follows: 1) using room temperature water in the waterpipe jar, 2) adding ice cubes to the water in the waterpipe jar, and 3) using a charcoal-free electronic waterpipe head to heat the tobacco instead of charcoal.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in breath Carbon monoxide (CO) levels from pre to post each of three waterpipe tobacco smoking sessions</measure>
    <time_frame>Assessment will be taken immediately before starting to smoke, and immediately at conclusion of each of the 3 smoking sessions.</time_frame>
    <description>The investigators will determine the differential effects of 3 waterpipe smoking practices on carbon monoxide (CO) exposure. We will measure breath CO using a Micro+ Smokerlyzer® CO monitor for exhaled CO before and after each of the 3 WP smoking sessions as follows: 1) using room temperature water in the WP jar, 2) adding ice cubes to the water in the WP jar, and 3) using a charcoal-free electronic WP head to heat the tobacco.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in pulmonary functions (PF) from pre to post each of three waterpipe tobacco smoking sessions.</measure>
    <time_frame>Assessment will be taken immediately before starting to smoke, and immediately at conclusion of each of the 3 smoking sessions.</time_frame>
    <description>The investigators will investigate the differential effects of WP smoking practices on pulmonary function tests and respiratory symptoms by measuring blood oxygen saturation (SO2), and conducting pulmonary functions (PF) testing using a portable spirometer/oximeter to determine the change in forced expiratory volume (FEV1), forced vital capacity (FVC), FEV1/FVC and Forced Expiratory Flow (FEF25-75%) post each of the 3 waterpipe tobacco smoking sessions as follows: 1) using room temperature water in the WP jar, 2) adding ice cubes to the water in the WP jar, and 3) using a charcoal-free electronic WP head to heat the tobacco.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Blood pressure, heart rate and respiratory rate from pre to post each of three waterpipe tobacco smoking sessions.</measure>
    <time_frame>Assessment will be taken immediately before starting to smoke, and immediately at conclusion of each of the 3 smoking sessions.</time_frame>
    <description>The investigators will investigate the differential effects of WP smoking practices on the cardiovascular system by measuring the change in blood pressure in mm/Hg, heart rate in beats/minute, and respiratory rate in number of breaths/minute, after each of the 3 WP smoking sessions as follows: 1) using room temperature water in the WP jar, 2) adding ice cubes to the water in the WP jar, and 3) using a charcoal-free electronic WP head to heat the tobacco.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in urinary Furan-BDA-NAL from pre to post each of three waterpipe tobacco smoking sessions</measure>
    <time_frame>Two days for each of the three smoking sessions. Smokers will provide two first morning spot urine samples, one urine sample on the morning of the day of the smoking session, and one urine sample on the morning of the following day</time_frame>
    <description>The investigators will assess change in urinary levels of Furan-BDA-NAL in pmol/ml and pmol/mg creatinine, which is the metabolite of furan, a liver toxicant and carcinogen, post the first waterpipe tobacco smoking session. Furan-BDA-NAL will be assessed in the provide two first morning spot urine samples, the day of the first smoking session and the day following the first smoking session.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>Waterpipe Smoking</condition>
  <arm_group>
    <arm_group_label>Waterpipe smoking</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In a repeated measures design, 50 adult male and female exclusive WP smokers will smoke WP tobacco weekly over a 3-week study period with 3 WP smoking practices.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>A total of 25 adult make and female nonsmokers will be recruited as a control.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Waterpipe smoking</intervention_name>
    <description>In a repeated measures design, 50 adult male and female exclusive WP tobacco smokers will smoke WP tobacco weekly over a 3-week study period with 3 WP smoking practices as follows: 1) using room temperature water in the WP jar, 2) adding ice cubes to the water in the WP jar, and 3) using a charcoal-free electronic WP head to heat the tobacco. Six Spot first morning urine samples will be provided by participants. Two urine samples per each of the 3 smoking sessions. Urine samples will be provided on the day of the WP tobacco smoking session and the following day. Physiological measures will be taken at Baseline during the office visit and before and after each of the 3 WP tobacco smoking sessions.</description>
    <arm_group_label>Waterpipe smoking</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for a Waterpipe Tobacco Smoker&#xD;
&#xD;
          -  Adult male or female exclusive waterpipe tobacco smoker&#xD;
&#xD;
          -  Smokes at least 1 waterpipe tobacco head per month&#xD;
&#xD;
          -  Smokes waterpipe tobacco at home&#xD;
&#xD;
          -  Age 21 years or older&#xD;
&#xD;
        Inclusion Criteria for a Non-Smoker&#xD;
&#xD;
          -  Adult male or female non-smoker&#xD;
&#xD;
          -  Lived in a 'non-smoker home' at least in the last month&#xD;
&#xD;
          -  Age 21 years or older&#xD;
&#xD;
        Inclusion Criteria for a Non-Smoker Home&#xD;
&#xD;
          -  No smokers have lived in in the past month&#xD;
&#xD;
          -  No visitors had smoked indoors/outdoors in the past month&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Major physical/psychiatric illnesses&#xD;
&#xD;
          -  Daily waterpipe smokers&#xD;
&#xD;
          -  Pregnant women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nada Kassem, DrPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>San Diego State University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Behavioral Epidemiology and Community Health</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>October 27, 2019</last_update_submitted>
  <last_update_submitted_qc>October 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>San Diego State University</investigator_affiliation>
    <investigator_full_name>Nada Kassem</investigator_full_name>
    <investigator_title>PI</investigator_title>
  </responsible_party>
  <keyword>waterpipe</keyword>
  <keyword>hookah</keyword>
  <keyword>NNAL</keyword>
  <keyword>SPMA</keyword>
  <keyword>1-HOP</keyword>
  <keyword>Furan-BDA-NAL</keyword>
  <keyword>Carbon monoxide</keyword>
  <keyword>Pulmonary Function</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03253653
org study id: R01DA042471-01
nct id: NCT03253653
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Waterpipe smoking is a tobacco use method in which smoke passes through a partially-filled
      water jar. Burning charcoal heats the waterpipe tobacco which produces the smoke that the
      user inhales. Waterpipe smoking was associated with increased risk for coronary heart and
      pulmonary diseases. This Waterpipe Study will inform the FDA on regulating waterpipe tobacco
      products and reduce the harm of it use. This study will be conducted at homes of hookah
      smokers, in natural settings, aimed to determine the effects of waterpipe smoking practices
      on physiological injury markers and biomarkers of toxicity of waterpipe tobacco smoking. The
      investigators will employ a repeated measures design. The investigators will recruit a sample
      of 50 adult male and female exclusive waterpipe smokers and a control sample of 25 male and
      female non-smokers via intercept interviews from San Diego County, California communities.
      Waterpipe smokers will smoke one waterpipe tobacco head (10g) of Starbuzz during 3 separate
      sessions with a 7-day washout period before each session, as follows: Session 1, Smoking
      waterpipe tobacco using 1 quick-light charcoal and room temperature water in the waterpipe
      jar, Session 2, Smoking waterpipe tobacco using 1 quick-light charcoal and adding ice cubes
      to the water in the waterpipe jar, and Session 3, Smoking waterpipe tobacco without charcoal
      using a charcoal-free electrically heated waterpipe head to heat the tobacco, and room
      temperature water in the waterpipe jar. The following data will be collected: a) Tobacco Use
      History, b) 4-week Tobacco Exposure Diary, c) Waterpipe Use Session Form, d) Carbon monoxide
      (CO) exposure: Micro+ Smokerlyzer® CO monitor will be used for exhaled CO pre and 2 minutes
      post each smoking session, e) Pulmonary function testing and measuring blood pressure, heart
      rate and respiratory rate, and f) 6 first morning urine samples: pre and post the 3 sessions
      to measure urinary cotinine, a metabolite of nicotine, 4-(methylnitrosamino)-1-
      (3-pyridyl)-1-butanol (NNAL) and NNAL-glucuronides (total NNAL), metabolites of the lung
      carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 1-hydroxypyrene (1-HOP), a
      metabolite of the genotoxic carcinogen pyrene, and S-phenylmercapturic acid (SPMA), a
      metabolite of the human hematotoxicant and leukemogen benzene. The investigators will explore
      exposure levels to furan, a liver toxicant and carcinogen, among waterpipe smokers via
      measuring its urinary metabolite Furan-BDA-NAL.
Globally, 1 in 3 adults or 1.2 billion people smoke. The World Health Organization (WHO)
      estimated that tobacco is responsible for the death of 1 in 10 adults worldwide, about 6
      million premature deaths each year. In the United States (U.S.), cigarette smoking is
      responsible for more than 480,000 deaths per year, including nearly 42,000 deaths resulting
      from secondhand smoke exposure. Tobacco use is the single leading most preventable cause of
      disease, disability, and mortality in the U.S. Tobacco research tends to focus on cigarettes;
      however, the rise in waterpipe (WP) tobacco use globally warrants studying all aspects of its
      toxicity. In 2005, the WHO called for a better understanding of WP tobacco smoking. In 2007,
      the American Lung Association labeled WP smoking as an emerging deadly trend. WP tobacco use
      was associated with increased risk for Chronic obstructive pulmonary disease (COPD), heart
      diseases, lung cancers, oral and esophageal cancers.

      COPD is a major public health problem leading to airflow obstruction. In the U.S., tobacco
      smoke is a key factor in the development of COPD, which was the third leading cause of death
      in the U.S. in 2014. WP smoking decreases respiratory quality of life in adults. Studies
      found that pulmonary function following WP smoking was impaired as measured by forced
      expiratory volume (FEV1), forced vital capacity (FVC), FEV1/FVC, and Forced Expiratory Flow
      (FEF25-75%). Studies investigating acute cardiovascular injury markers due to WP smoking
      showed significant increases in heart rate, and in systolic and diastolic blood pressure.

      In 2014, the U.S. Food and Drug Administration (FDA) initiated regulation WP tobacco. The FDA
      proposed that the manufacturers of WP tobacco disclose to the FDA their products' ingredients
      and report harmful and potentially harmful constituents (HPHCs). A review study showed that
      exposures to HPHCs are 10-100 times higher in WP tobacco smoke than in cigarette smoke. To
      inform the FDA on the regulation of WP tobacco products, and reduce the harm of it use, the
      investigators propose a Waterpipe Project in a natural setting to determine the differential
      effects of WP smoking practices on physiological injury markers, and biomarkers of toxicants
      and carcinogens.

      Worldwide, the WP is used in Africa, Asia, China, India, and the Middle East. Adolescents and
      young adults in the U.S. are experimenting with WP smoking. The 2014 U.S. National College
      Health Assessment II found that nearly one third of U.S. undergraduate college students
      (38.2% of men and 31.4% of women), reported ever using WP tobacco, and 11.6% of men and 8.3%
      of women reported current use (past 30 days). Among high school students, the 2013 U.S.
      National Youth Tobacco Survey showed that 15.1% of boys and 13.5% of girls reported ever WP
      use.

      The WP (hookah) consists of a head, a body, a hose, and a water jar. The tobacco is placed in
      the head and covered with a perforated aluminum foil to allow air-flow. Burning charcoal is
      placed on top of the aluminum foil. Upon deep inhalation via the WP hose, suction forces hot
      air through the head, heating and combusting the tobacco to produce the smoke that is forced
      down the WP body, into and out of the water in the airtight jar, and through the hose into
      the smoker's mouth and respiratory system. Smokers inhale charcoal toxicant emissions in
      addition to those from the WP tobacco. Charcoal combustion contributes greatly to benzene,
      carbon monoxide (CO) and carcinogenic yields. CO is a smoke toxicant that reduces the blood's
      ability to transport oxygen to various organs, including the brain, and can cause dizziness,
      headache, syncope and nausea.

      A charcoal-free electrically heated WP head is commercially available. Users were satisfied
      with this device because they did not have to deal with charcoal fire hazardous ambers and
      ashes, in addition to enjoying the feeling of reduced harm. WP smokers normally use room
      temperature water in the WP jar. However, other liquid media are gaining in popularity.
      According to anecdotal evidence, "adding ice cubes in the WP jar has an enjoyable cooling
      effect to the inhaled smoke". Smokers practice adding ice cubes at home, and for an extra
      charge hookah lounges provide this option for customers. Toxic chemicals in WP tobacco smoke
      include cotinine, a metabolite of the addictive drug nicotine;
      4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and NNAL-glucuronides (total NNAL);
      metabolites of the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK);
      1-hydroxypyrene (1-HOP), a metabolite of the genotoxic carcinogen pyrene; and
      S-phenylmercapturic acid (SPMA), a metabolite of the human hematotoxicant and leukemogen
      benzene; and Furan-BDA-NAL, a metabolite of the carcinogen furan.

      METHODS. will compare exhaled CO, pulmonary functions, blood pressure, heart rate and
      respiratory rate, and urinary levels of cotinine, NNAL, SPMA, and 1-HOP in first void WP
      smoker urine samples the morning of, and the morning after a WP smoking session across 3
      smoking practices. The investigators will recruit a sample of 50 adult male and female
      exclusive WP smokers and a control sample of 25 male and female non-smokers. Participants
      will be recruited and qualified via random intercept screen interviews from San Diego County,
      California communities. Over a 3-week study period, WP smokers will smoke one WP tobacco head
      (10g) of Starbuzz during 3 separate sessions with a 7-day washout period before each session
      in their home in a natural setting: Week 1-Session 1, WP smokers will smoke using 1
      quick-light charcoal and room temperature water in the WP jar, Week 2-Session 2, WP smokers
      will smoke using 1 quick-light charcoal but adding ice cubes to the water in the WP jar, Week
      3-Session 3, WP smokers will smoke WP tobacco without charcoal using the electric WP head and
      room temperature water. The investigators will collect the following forms: a) Tobacco Use
      History; b) 3-week Tobacco Use and Exposure Diaries; c) WP Smoking Session Day and Exposure
      Form; and will measure d) CO exposure: Micro+ Smokerlyzer® CO monitor will be used for
      exhaled CO two minutes pre and post each smoking session; e) Pulmonary function testing and
      measuring blood pressure, heart rate and respiratory rate pre and post each smoking session;
      and f) 6 first morning urine samples: pre and post the 3 sessions to measure urinary
      cotinine, NNAL, 1-HOP, SPMA, and Furan-BDA-NAL. Efforts will be made to recruit equal samples
      of males and females. Flexible scheduling for study activities where applicable. Proration of
      incentives will apply for completed activities.

      The 3-Week Study period: comprised of 3 WP smoking sessions with 7-day wash-out periods

      WP Smoking Session 1. Day 1 - Office Visit: The Office Visit is expected to take between 60
      and 90 minutes where potential participants will be trained on the study activities. Consent
      will be obtained, study forms will be completed, and study related materials such as forms
      and urine cups will be provided. Scheduling will be arranged for the 3 WP smoking sessions
      and corresponding home visits. Saliva Test: Trained by the PI, the RAs will use NicAlert, an
      accurate and valid commercial semi-quantitative instant saliva cotinine test, to validate
      non-smoking status, which the investigators used successfully in their previous studies. The
      following physiological baseline data will be collected: pulmonary functions, blood pressure,
      heart rate and respiratory rate. Days 2 - 6: The RAs will contact participants by phone on
      the 4th day to confirm adherence to the 7-wash-out period and diaries, and on the 6th day to
      remind participants to collect the first morning urine sample on day 7, and to arrange for a
      home visit for the first WP smoking session. Day 7: WP smoking session 1. WP smokers will
      provide one first morning urine sample and store it in their refrigerator (freezer section).
      WP smokers will smoke WP tobacco (10 grams) as they normally do using charcoal and room
      temperature water in the water jar. The RAs will collect expired CO levels 2 minutes before
      and 2 minutes after concluding smoking, and will measure pulmonary functions, blood pressure,
      heart rate and respiratory rate thereafter. Day 8: Participants will provide a first morning
      urine sample. The RAs will pick up the 2 urine samples (frozen in a cooler to transfer them
      to the research center laboratory), and arrange for the 2nd WP smoking session home visit,
      provide forms, urine cups package for week 2 of the study. WP Smoking Session 2. Days 1
      through 7 are similar to session 1 with the exception that the RAs will add one tray of ice
      cubes and water in the WP jar. The RAs will arrange for a training session to use the
      charcoal-free electrically heated WP head. WP Smoking Session 3. Days 1 through 7 are similar
      to session 1 using room temperature water in the WP jar, however using the charcoal-free
      electrically heated WP head instead of using charcoal. During the last visit, the day after
      the 3rd smoking session, the RAs will interview participants to complete the Illnesses and
      Health Care History Form, pick up the final urine samples, and thank the participants.
intervention model: Parallel Assignment
intervention model description: The investigators will employ a repeated measures design. A sample of 50 adult male and female exclusive WP smokers and a control sample of 25 male and female non-smokers will be recruited. Over a 3-week study, WP smokers will smoke one WP tobacco head during each of 3 separate WP smoking sessions with a 7-day washout period before each session. Session 1, WP smokers will smoke using 1 quick-light charcoal and room temperature water in the WP jar; Session 2, WP smokers will smoke using 1 quick-light charcoal but adding ice cubes to the water in the WP jar; Session 3, WP smokers will smoke WP tobacco without charcoal using an electric WP head and room temperature water. Physiological effects, carbon monoxide exposure and biomarkers of toxicants and carcinogens related to WP tobacco smoking practices will be compared.
primary purpose: Other
masking: None (Open Label)
measure: Change in urinary cotinine from pre to post each of three waterpipe tobacco smoking sessions
time frame: Two days for each of the three smoking sessions. Smokers will provide two first morning spot urine samples, one urine sample on the morning of the day of the smoking session, and one urine sample on the morning of the following day.
description: The investigators will assess change in urinary levels of cotinine in ng/ml and ng/mg creatinine, which is the metabolite of the addictive drug nicotine, post each of three waterpipe tobacco smoking sessions. For each of the three smoking sessions, smokers will provide two first morning spot urine samples, the day of the smoking session and the following morning. The three waterpipe tobacco smoking sessions are as follows: 1) using room temperature water in the waterpipe jar, 2) adding ice cubes to the water in the waterpipe jar, and 3) using a charcoal-free electronic waterpipe head to heat the tobacco instead of charcoal.
measure: Change in urinary NNAL from pre to post each of three waterpipe tobacco smoking sessions
time frame: Two days for each of the three smoking sessions. Smokers will provide two first morning spot urine samples, one urine sample on the morning of the day of the smoking session, and one urine sample on the morning of the following day.
description: The investigators will assess change in urinary levels of NNAL in pg/ml and ng/mg creatinine, which is the metabolite of NNK, a tobacco specific pulmonary carcinogen, post each of three waterpipe tobacco smoking sessions. For each of the three smoking sessions, smokers will provide two first morning spot urine samples, the day of the smoking session and the following morning. The three waterpipe tobacco smoking sessions are as follows: 1) using room temperature water in the waterpipe jar, 2) adding ice cubes to the water in the waterpipe jar, and 3) using a charcoal-free electronic waterpipe head to heat the tobacco instead of charcoal.
measure: Change in urinary SPMA from pre to post each of three waterpipe tobacco smoking sessions
time frame: Two days for each of the three smoking sessions. Smokers will provide two first morning spot urine samples, one urine sample on the morning of the day of the smoking session, and one urine sample on the morning of the following day.
description: The investigators will assess change in urinary levels of SPMA in pmol/ml and pmol/mg creatinine, which is the metabolite of benzene, the human hematotoxicant and leukemogen, post each of three waterpipe tobacco smoking sessions. For each of the three smoking sessions, smokers will provide two first morning spot urine samples, the day of the smoking session and the following morning. The three waterpipe tobacco smoking sessions are as follows: 1) using room temperature water in the waterpipe jar, 2) adding ice cubes to the water in the waterpipe jar, and 3) using a charcoal-free electronic waterpipe head to heat the tobacco instead of charcoal.
measure: Change in urinary 1-HOP from pre to post each of three waterpipe tobacco smoking sessions
time frame: Two days for each of the three smoking sessions. Smokers will provide two first morning spot urine samples, one urine sample on the morning of the day of the smoking session, and one urine sample on the morning of the following day.
description: The investigators will assess change in urinary levels of 1-HOP in pmol/ml and pmol/mg creatinine, which is the metabolite of pyrene, a genotoxic carcinogen, post each of three waterpipe tobacco smoking sessions. For each of the three smoking sessions, smokers will provide two first morning spot urine samples, the day of the smoking session and the following morning. The three waterpipe tobacco smoking sessions are as follows: 1) using room temperature water in the waterpipe jar, 2) adding ice cubes to the water in the waterpipe jar, and 3) using a charcoal-free electronic waterpipe head to heat the tobacco instead of charcoal.
measure: Change in breath Carbon monoxide (CO) levels from pre to post each of three waterpipe tobacco smoking sessions
time frame: Assessment will be taken immediately before starting to smoke, and immediately at conclusion of each of the 3 smoking sessions.
description: The investigators will determine the differential effects of 3 waterpipe smoking practices on carbon monoxide (CO) exposure. We will measure breath CO using a Micro+ Smokerlyzer® CO monitor for exhaled CO before and after each of the 3 WP smoking sessions as follows: 1) using room temperature water in the WP jar, 2) adding ice cubes to the water in the WP jar, and 3) using a charcoal-free electronic WP head to heat the tobacco.
measure: Change in pulmonary functions (PF) from pre to post each of three waterpipe tobacco smoking sessions.
time frame: Assessment will be taken immediately before starting to smoke, and immediately at conclusion of each of the 3 smoking sessions.
description: The investigators will investigate the differential effects of WP smoking practices on pulmonary function tests and respiratory symptoms by measuring blood oxygen saturation (SO2), and conducting pulmonary functions (PF) testing using a portable spirometer/oximeter to determine the change in forced expiratory volume (FEV1), forced vital capacity (FVC), FEV1/FVC and Forced Expiratory Flow (FEF25-75%) post each of the 3 waterpipe tobacco smoking sessions as follows: 1) using room temperature water in the WP jar, 2) adding ice cubes to the water in the WP jar, and 3) using a charcoal-free electronic WP head to heat the tobacco.
measure: Change in Blood pressure, heart rate and respiratory rate from pre to post each of three waterpipe tobacco smoking sessions.
time frame: Assessment will be taken immediately before starting to smoke, and immediately at conclusion of each of the 3 smoking sessions.
description: The investigators will investigate the differential effects of WP smoking practices on the cardiovascular system by measuring the change in blood pressure in mm/Hg, heart rate in beats/minute, and respiratory rate in number of breaths/minute, after each of the 3 WP smoking sessions as follows: 1) using room temperature water in the WP jar, 2) adding ice cubes to the water in the WP jar, and 3) using a charcoal-free electronic WP head to heat the tobacco.
measure: Change in urinary Furan-BDA-NAL from pre to post each of three waterpipe tobacco smoking sessions
time frame: Two days for each of the three smoking sessions. Smokers will provide two first morning spot urine samples, one urine sample on the morning of the day of the smoking session, and one urine sample on the morning of the following day
description: The investigators will assess change in urinary levels of Furan-BDA-NAL in pmol/ml and pmol/mg creatinine, which is the metabolite of furan, a liver toxicant and carcinogen, post the first waterpipe tobacco smoking session. Furan-BDA-NAL will be assessed in the provide two first morning spot urine samples, the day of the first smoking session and the day following the first smoking session.
arm group label: Waterpipe smoking
arm group type: Experimental
description: In a repeated measures design, 50 adult male and female exclusive WP smokers will smoke WP tobacco weekly over a 3-week study period with 3 WP smoking practices.
arm group label: Control
arm group type: No Intervention
description: A total of 25 adult make and female nonsmokers will be recruited as a control.
intervention type: Device
intervention name: Waterpipe smoking
description: In a repeated measures design, 50 adult male and female exclusive WP tobacco smokers will smoke WP tobacco weekly over a 3-week study period with 3 WP smoking practices as follows: 1) using room temperature water in the WP jar, 2) adding ice cubes to the water in the WP jar, and 3) using a charcoal-free electronic WP head to heat the tobacco. Six Spot first morning urine samples will be provided by participants. Two urine samples per each of the 3 smoking sessions. Urine samples will be provided on the day of the WP tobacco smoking session and the following day. Physiological measures will be taken at Baseline during the office visit and before and after each of the 3 WP tobacco smoking sessions.
arm group label: Waterpipe smoking
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Nada Kassem, DrPH
role: Principal Investigator
affiliation: San Diego State University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: San Diego State University
investigator full name: Nada Kassem
investigator title: PI
sharing ipd: No