<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/NCT02990455</url>
  </required_header>
  <id_info>
    <org_study_id>BMI-202181</org_study_id>
    <nct_id>NCT02990455</nct_id>
  </id_info>
  <brief_title>Reduced Nicotine Cigarettes in Smokers With and Without Alcohol Use Disorder</brief_title>
  <acronym>RedNic</acronym>
  <official_title>Reduced Nicotine Cigarettes in Smokers With and Without Alcohol Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Battelle Memorial Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Battelle Memorial Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The proposed research will investigate whether smokers with vs. without current at-risk&#xD;
      alcohol drinking (ARD) respond to reduced nicotine cigarettes by increasing their alcohol&#xD;
      consumption or smoke exposure, thereby diminishing the hypothesized public health benefit of&#xD;
      these new products.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The current proposal examines response to two RNCs, one with low nicotine content (RNC Low;&#xD;
      0.03mg) and one with moderate nicotine content (RNC Moderate; 0.8mg) in daily smokers with&#xD;
      and without ARD. Participants (N = 70) will attend a total of five visits to the laboratory.&#xD;
      The first visit will be to classify participants as either ARD (n = 35) or Non ARD (n = 35)&#xD;
      and gather baseline data. Participants will be assigned to undergo two experimental&#xD;
      conditions (i.e., exclusive smoking of RNC Low or Moderate in their home environment for 7&#xD;
      days) in a double-blind, randomized, crossover design. The two experimental conditions will&#xD;
      be separated by a 7-day period of return to smoking of participants' own brand of cigarette.&#xD;
      On the first and last day of each of the two experimental conditions, participants will smoke&#xD;
      the assigned RNC in the laboratory, and data on toxicant exposure (i.e., boost in exhaled&#xD;
      carbon monoxide and plasma nicotine and cotinine; solanesol from smoked cigarette butts),&#xD;
      subjective acceptability (i.e., subjective response; risk perceptions; relative reinforcing&#xD;
      efficacy); and smoking compensation (i.e., smoking topography measures) related to the smoked&#xD;
      RNC will be collected. During each 7-day period of exposure to the RNCs, participants will&#xD;
      provide daily data on alcohol and nicotine use, nicotine withdrawal, smoking urge, and&#xD;
      alcohol urge via telephone-based Interactive Voice Response technology. The strength of our&#xD;
      study design is that we can evaluate both between-group (i.e., ARD vs. Non ARD) and&#xD;
      within-person (i.e., RNC Low vs. Moderate) differences in response to RNCs and, furthermore,&#xD;
      can examine whether increased nicotine withdrawal, smoking urge, and alcohol urge mediate the&#xD;
      relation between decreased nicotine exposure and alcohol consumption. Results from this study&#xD;
      will show what mechanisms underlying drinking and smoking may need to be addressed in future&#xD;
      integrated interventions for both problems and will immediately inform the practical&#xD;
      implementation of market-wide reductions in cigarette nicotine content among smokers with&#xD;
      ARD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 14, 2017</start_date>
  <completion_date type="Actual">April 21, 2021</completion_date>
  <primary_completion_date type="Actual">April 21, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Alcohol drinks per day</measure>
    <time_frame>7 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Toxicant exposure</measure>
    <time_frame>7 days</time_frame>
    <description>(1) boost in (a) exhaled carbon monoxide, (b) plasma nicotine, and (c) plasma cotinine, and (2) solanesol after laboratory smoking</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective acceptability</measure>
    <time_frame>7 days</time_frame>
    <description>subjective response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Smoking compensation</measure>
    <time_frame>7 days</time_frame>
    <description>number of cigarettes per day during each 7-day period</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Alcohol Drinking</condition>
  <condition>Cigarette Smoking Toxicity</condition>
  <arm_group>
    <arm_group_label>Reduced Nicotine Cigarette - Moderate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nicotine Research Cigarette Drug Supply Program Category Codes NRC600 and NRC601 (menthol); each cigarette contains 0.8mg nicotine; participants will be instructed to smoke these cigarettes according to their usual smoking patterns</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Reduced Nicotine Cigarette - Low</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nicotine Research Cigarette Drug Supply Program Category Codes NRC102 and NRC103 (menthol); each cigarette contains 0.03mg nicotine; participants will be instructed to smoke these cigarettes according to their usual smoking patterns</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Reduced nicotine cigarettes</intervention_name>
    <description>Participants will be assigned to undergo two experimental conditions (i.e., exclusive smoking of RNC Low or Moderate in their home environment for 7 days) in a double-blind, randomized, crossover design. The two experimental conditions will be separated by a 7-day period of return to smoking of participants' own brand of cigarette.</description>
    <arm_group_label>Reduced Nicotine Cigarette - Low</arm_group_label>
    <arm_group_label>Reduced Nicotine Cigarette - Moderate</arm_group_label>
    <other_name>Nicotine research cigarettes</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ages 21-65;&#xD;
&#xD;
          -  Smokes ≥ 10 cigarettes/day for ≥ 2 years;&#xD;
&#xD;
          -  Has no immediate plans to quit drinking or smoking; and&#xD;
&#xD;
          -  Sufficient understanding of informed consent form and study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has or is at-risk of serious alcohol-related consequences, defined as any of the&#xD;
             following:&#xD;
&#xD;
               1. Meets DSM-5 criteria for current alcohol use disorder with the presence of 6 or&#xD;
                  more symptoms (i.e., current severity of severe)&#xD;
&#xD;
               2. Has a Clinical Institute Withdrawal Assessment scale score of ≥8,&#xD;
&#xD;
               3. Self-report of history of seizures, delirium, or hallucinations during alcohol&#xD;
                  withdrawal;&#xD;
&#xD;
               4. Self-report of drinking to avoid withdrawal symptoms, or&#xD;
&#xD;
               5. Self-report of a history of alcohol withdrawal treatment.&#xD;
&#xD;
          -  Women if pregnant, lactating, or not using a reliable form of birth control;&#xD;
&#xD;
          -  Has current serious psychiatric disorder;&#xD;
&#xD;
          -  Has DSM-5 current severe substance use disorder, other than nicotine;&#xD;
&#xD;
          -  Has current use of smokeless tobacco, pipes, cigars, e-cigarettes, or nicotine&#xD;
             replacement products;&#xD;
&#xD;
          -  Displays clinically evident intoxication on any study visit, confirmed by breathalyzer&#xD;
             test (breath alcohol level (BAL)&gt;0.02 mg%);&#xD;
&#xD;
          -  Has difficulties with blood draws or poor venous access; or&#xD;
&#xD;
          -  Has significant smoking-related disease (by history).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Battelle Memorial Institute</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>December 7, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 13, 2016</study_first_posted>
  <last_update_submitted>September 27, 2021</last_update_submitted>
  <last_update_submitted_qc>September 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>alcohol</keyword>
  <keyword>drinking</keyword>
  <keyword>smoking</keyword>
  <keyword>cigarette</keyword>
  <keyword>nicotine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Alcohol Drinking</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nicotine</mesh_term>
  </intervention_browse>
  <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/NCT02990455
org study id: BMI-202181
nct id: NCT02990455
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The proposed research will investigate whether smokers with vs. without current at-risk
      alcohol drinking (ARD) respond to reduced nicotine cigarettes by increasing their alcohol
      consumption or smoke exposure, thereby diminishing the hypothesized public health benefit of
      these new products.
The current proposal examines response to two RNCs, one with low nicotine content (RNC Low;
      0.03mg) and one with moderate nicotine content (RNC Moderate; 0.8mg) in daily smokers with
      and without ARD. Participants (N = 70) will attend a total of five visits to the laboratory.
      The first visit will be to classify participants as either ARD (n = 35) or Non ARD (n = 35)
      and gather baseline data. Participants will be assigned to undergo two experimental
      conditions (i.e., exclusive smoking of RNC Low or Moderate in their home environment for 7
      days) in a double-blind, randomized, crossover design. The two experimental conditions will
      be separated by a 7-day period of return to smoking of participants' own brand of cigarette.
      On the first and last day of each of the two experimental conditions, participants will smoke
      the assigned RNC in the laboratory, and data on toxicant exposure (i.e., boost in exhaled
      carbon monoxide and plasma nicotine and cotinine; solanesol from smoked cigarette butts),
      subjective acceptability (i.e., subjective response; risk perceptions; relative reinforcing
      efficacy); and smoking compensation (i.e., smoking topography measures) related to the smoked
      RNC will be collected. During each 7-day period of exposure to the RNCs, participants will
      provide daily data on alcohol and nicotine use, nicotine withdrawal, smoking urge, and
      alcohol urge via telephone-based Interactive Voice Response technology. The strength of our
      study design is that we can evaluate both between-group (i.e., ARD vs. Non ARD) and
      within-person (i.e., RNC Low vs. Moderate) differences in response to RNCs and, furthermore,
      can examine whether increased nicotine withdrawal, smoking urge, and alcohol urge mediate the
      relation between decreased nicotine exposure and alcohol consumption. Results from this study
      will show what mechanisms underlying drinking and smoking may need to be addressed in future
      integrated interventions for both problems and will immediately inform the practical
      implementation of market-wide reductions in cigarette nicotine content among smokers with
      ARD.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Alcohol drinks per day
time frame: 7 days
measure: Toxicant exposure
time frame: 7 days
description: (1) boost in (a) exhaled carbon monoxide, (b) plasma nicotine, and (c) plasma cotinine, and (2) solanesol after laboratory smoking
measure: Subjective acceptability
time frame: 7 days
description: subjective response
measure: Smoking compensation
time frame: 7 days
description: number of cigarettes per day during each 7-day period
arm group label: Reduced Nicotine Cigarette - Moderate
arm group type: Experimental
description: Nicotine Research Cigarette Drug Supply Program Category Codes NRC600 and NRC601 (menthol); each cigarette contains 0.8mg nicotine; participants will be instructed to smoke these cigarettes according to their usual smoking patterns
arm group label: Reduced Nicotine Cigarette - Low
arm group type: Experimental
description: Nicotine Research Cigarette Drug Supply Program Category Codes NRC102 and NRC103 (menthol); each cigarette contains 0.03mg nicotine; participants will be instructed to smoke these cigarettes according to their usual smoking patterns
intervention type: Drug
intervention name: Reduced nicotine cigarettes
description: Participants will be assigned to undergo two experimental conditions (i.e., exclusive smoking of RNC Low or Moderate in their home environment for 7 days) in a double-blind, randomized, crossover design. The two experimental conditions will be separated by a 7-day period of return to smoking of participants' own brand of cigarette.
arm group label: Reduced Nicotine Cigarette - Low
arm group label: Reduced Nicotine Cigarette - Moderate
other name: Nicotine research cigarettes
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alcoholism
mesh term: Alcohol Drinking
mesh term: Nicotine
sharing ipd: No