<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/NCT01669538</url>
  </required_header>
  <id_info>
    <org_study_id>815789</org_study_id>
    <secondary_id>UPCC15912</secondary_id>
    <secondary_id>K23DA035295</secondary_id>
    <nct_id>NCT01669538</nct_id>
    <nct_alias>NCT01845961</nct_alias>
  </id_info>
  <brief_title>Effect of Galantamine on Short-term Abstinence</brief_title>
  <acronym>GAL-K</acronym>
  <official_title>Repurposing Cholinesterase Inhibitors for Smoking Cessation.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Center for Research Resources (NCRR)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, double-blind, placebo-controlled study to test whether a medication&#xD;
      called galantamine (Brand Name: Razadyne) will help smokers quit and whether it reduces&#xD;
      cognitive problems that smokers experience during a quit attempt.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Galantamine, an FDA-approved treatment for Alzheimer's disease, is used to treat cognitive&#xD;
      impairment by enhancing acetylcholine through inhibition of the enzyme, acetylcholinesterase.&#xD;
      We propose randomized double-blind placebo-controlled study of short-term (23 days) treatment&#xD;
      with galantamine.&#xD;
&#xD;
      Eighty chronic smokers will complete a validated procedure for screening new medications. An&#xD;
      equal number of subjects will be assigned to one of two groups: galantamine-ER or placebo.&#xD;
      Participants in both groups will take one capsule each day and follow the same procedures.&#xD;
      This is not a cross-over trial.&#xD;
&#xD;
      For participants in the galantamine group, following an initial 1-week drug run-up phase (8mg&#xD;
      daily of galantamine-ER), the medication dose will be increased to 16mg daily of&#xD;
      galantamine-ER for the remainder of the study (up to Day 23).&#xD;
&#xD;
      On Day 15, smokers will begin a mandatory 24-hour abstinence period, which will be followed&#xD;
      by a programmed smoking lapse on Day 16. Smokers will then be instructed to abstain for the&#xD;
      following 7 days (observed abstinence). Following completion of the study, participants will&#xD;
      be offered standard smoking cessation treatment.&#xD;
&#xD;
      On Days 0 (Baseline), 14, and 16, subjects will perform the following computer tasks: a&#xD;
      working memory task (Visual/Spatial N-Back), sustained attention tasks (Penn Continuous&#xD;
      Performance Task [PCPT-nl] and XO Reaction Time Task), a recall memory task (Word&#xD;
      Recognition), an interference control task (Stroop test), and a response inhibition task&#xD;
      (Stop Signal Task).&#xD;
&#xD;
      The primary outcome is to identify changes in behavioral performance and subjective symptoms&#xD;
      following two weeks treatment of galantamine and after 24 hours of abstinence, compared to&#xD;
      baseline.&#xD;
&#xD;
      This study will provide information about the role of the cholinergic system during brief&#xD;
      abstinence and whether enhancing acetylcholine reduces abstinence-induced cognitive symptoms&#xD;
      that promote smoking relapse. Information obtained in this study may further establish&#xD;
      cognitive performance measures as endophenotypes for nicotine dependence.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">November 2017</completion_date>
  <primary_completion_date type="Actual">November 2017</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total Number of Smoke-free Days (Biochemically Verified) During a 7-day Quit Attempt.</measure>
    <time_frame>Days 17-23</time_frame>
    <description>Day 17 will be the beginning of a 7-day quit attempt, during which the total number of days of abstinence will be assessed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cognitive Performance</measure>
    <time_frame>Baseline (Day 0), Day 14 (day before start of 24-hour abstinence period), Day 16 (after 24-hour abstinence period ends)</time_frame>
    <description>Participants will complete neurocognitive tests designed to test working memory and attention. These tests are similar to computer games, in that participants will push a button in response to the pictures they see.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective Symptoms</measure>
    <time_frame>Baseline (day 0), Days 7, 14, 16, 17, 19, 21, and 23</time_frame>
    <description>Smoking urges [Questionnaire of Smoking Urges-Brief; QSU-B; 10-items rated on a 7-point scale (1=strongly disagree, 7=strongly agree) and summed for total score (range: 10-70). Higher scores=greater urge to smoke.] Negative mood [Negative Affect scale (10 items) from the Positive and Negative Affect Schedule; PANAS; 20-item Likert-format measure; The subscale was summed to create a summary score (range: 10-50); Lower negative affect indicates better outcomes.] Nicotine withdrawal [Minnesota Nicotine Withdrawal Scale-Revised; MNWS-R; 15 symptoms are rated on intensity with the following scale: 0=none, 1=slight, 2=mild, 3=moderate, 4=severe. The first 9 items are summed for total score (range: 0-36); higher scores=more severe withdrawal.].&#xD;
Measures assessed at the following visits: Baseline; Day 7 (monitoring visit); Day 14 (Day before 24-hour abstinence period), Day 16 (after 24-hour abstinence period), and Days 17-23 (7-day quit attempt).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Common Side Effects of Galantamine Check List</measure>
    <time_frame>Baseline (day 0), Days 7, 14, 16, 17, 19, 21, and 23</time_frame>
    <description>Subjects completed a side effect checklist at every in-person study visit over the course of the treatment period. Subjects rated the severity of 37 common side effects of galantamine on the following scale: 0=none, 1=mild, 2=moderate, 3=severe. The average of all items was used to create a summary side effect score (range for total summary score 0-3). Higher scores indicate greater severity of side effects.&#xD;
Side effects of galantamine were assessed at the following in-person sessions: Baseline session; Day 7 (brief monitoring visit); Day 14 (Day before 24-hour abstinence period), Day 16 (after 24-hour abstinence period), and Days 17-23 (during the 7-day quit attempt).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">98</enrollment>
  <condition>Tobacco Use Disorder</condition>
  <arm_group>
    <arm_group_label>Galantamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Galantamine hydrobromide-ER (extended release) is currently marketed for the treatment of Alzheimer's disease. The dosing regimen follows the FDA-approved guidelines. For the first week of study treatment, participants will take 8mg daily of galantamine-ER, preferably with food. 8mg is the lowest dose and this period is designed to introduce the medication into their system. After the initial week, participants will increase their daily dose to 16mg. They will remain on 16mg daily until the end of the treatment period for a total of 23 days on active study medication.&#xD;
Galantamine will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants assigned to the placebo (sugar pill) arm will take one capsule daily, preferably with food, for a total of 23 days. They will follow the same instructions and complete the same procedures as those in the active treatment.&#xD;
Placebo ingredients (sucrose filler and gel capsules) will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Galantamine</intervention_name>
    <arm_group_label>Galantamine</arm_group_label>
    <other_name>Galantamine hydrobromide ER</other_name>
    <other_name>Razadyne ER</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Sugar pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Smokers who are between 18 and 60 years of age who self-report smoking at least 10&#xD;
             cigarettes (menthol and non-menthol) per day for at least the last 6 months.&#xD;
&#xD;
          2. Interest in quitting smoking in the next 2 to 6 months.&#xD;
&#xD;
          3. Healthy as determined by the Study Physician, based on a medical evaluation including&#xD;
             medical history and physical examination, and psychiatric evaluation.&#xD;
&#xD;
          4. Capable of giving written informed consent, which includes compliance with the&#xD;
             requirements and restrictions listed in the combined consent and HIPAA form.&#xD;
&#xD;
          5. Women of childbearing potential must consent to use a medically accepted method of&#xD;
             birth control while participating in the study (e.g., condoms and spermicide, oral&#xD;
             contraceptive, Depo-provera injection, contraceptive patch, tubal ligation).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Smoking behavior&#xD;
&#xD;
               1. Use of chewing tobacco, snuff, and/or snus.&#xD;
&#xD;
               2. Current enrollment in a smoking cessation program, or use of other smoking&#xD;
                  cessation medications in the last month or plans to do either in the next 2&#xD;
                  months.&#xD;
&#xD;
               3. Provide a carbon monoxide (CO) breath sample reading less than 10 parts per&#xD;
                  million (ppm) at either the Intake or Baseline visits.&#xD;
&#xD;
          2. Alcohol/Drugs&#xD;
&#xD;
               1. Lifetime history of substance abuse (other than nicotine) and/or currently&#xD;
                  receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine,&#xD;
                  stimulants, PCP, benzodiazepines, or study-prohibited medications/recreational&#xD;
                  drugs) as determined by self-report during the phone screen and/or through the&#xD;
                  MINI during the Intake visit.&#xD;
&#xD;
               2. Current alcohol consumption that exceeds 25 standard drinks/week over the past 6&#xD;
                  months.&#xD;
&#xD;
               3. Providing a breath alcohol concentration (BrAC) reading of greater than or equal&#xD;
                  to 0.01 at the Intake, Baseline, or Testing Days.&#xD;
&#xD;
               4. A positive urine drug screen for cocaine, amphetamines, methamphetamines,&#xD;
                  benzodiazepines, PCP, methadone, barbiturates, and opiates at the Intake visit,&#xD;
                  Baseline visit, or the Testing days.&#xD;
&#xD;
          3. Medical&#xD;
&#xD;
               1. Women who are pregnant, planning a pregnancy in the next 3 months, or lactating;&#xD;
                  all female subjects shall undergo a urine pregnancy test at the Intake visit and&#xD;
                  must agree in writing to use an approved method of contraception. Following&#xD;
                  enrollment, pregnancy tests will be conducted at the Baseline visit and Testing&#xD;
                  days for all female subjects of child-bearing potential.&#xD;
&#xD;
               2. Diagnosis of Alzheimer's Disease or dementia.&#xD;
&#xD;
               3. Current treatment of cancer or diagnosed with cancer (except basal cell&#xD;
                  carcinoma) in the past 6 months.&#xD;
&#xD;
               4. Liver/kidney failure, peptic ulcer disease, benign prostate hypertrophy.&#xD;
&#xD;
               5. Asthma or chronic obstructive pulmonary disease (COPD).&#xD;
&#xD;
               6. History (last 6 months) of abnormal heart rhythms, tachycardia and/or&#xD;
                  cardiovascular disease (stroke, angina, heart attack). These conditions will be&#xD;
                  evaluated on a case by case basis by the Study Physician/Health Care Provider.&#xD;
&#xD;
               7. Serious or unstable disease within the past 6 months, as determined by the Study&#xD;
                  Physician/Health Care Provider.&#xD;
&#xD;
               8. Clinically significant abnormalities within physical examination and vital signs&#xD;
                  at Medical Screen. Abnormalities will be assessed by the Study Physician/Health&#xD;
                  Care Provider and eligibility will be determined on a case-by-case basis.&#xD;
&#xD;
               9. Any impairment (physical and/or neurological) including visual or other&#xD;
                  impairment preventing cognitive task performance.&#xD;
&#xD;
              10. Uncontrolled high blood pressure (Systolic BP greater than 160 and/or Diastolic&#xD;
                  BP greater than 100).&#xD;
&#xD;
              11. Hearing impairment, significant hearing loss (more than 20% in either ear),&#xD;
                  cochlear implants, or bi-lateral hearing aids.&#xD;
&#xD;
              12. History of brain injury.&#xD;
&#xD;
              13. History of epilepsy or a seizure disorder.&#xD;
&#xD;
              14. Color Blindness.&#xD;
&#xD;
              15. Low or borderline intellectual functioning - determined by receiving a score of&#xD;
                  less than 90 on the Shipley Institute of Living Scale (SILS) which correlates&#xD;
                  with the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Estimated IQ Test&#xD;
                  (administered at the Intake visit).&#xD;
&#xD;
          4. Psychiatric Exclusions (determined by self-report on phone screen and/or through the&#xD;
             MINI during the Intake visit)&#xD;
&#xD;
               1. Current diagnosis of major depression. Persons with a history of major&#xD;
                  depression, in remission for 6 months or longer, are eligible, provided they are&#xD;
                  not excluded based on medications (below).&#xD;
&#xD;
               2. Suicide risk score on MINI greater than 0.&#xD;
&#xD;
               3. History or current diagnosis of schizophrenia, psychosis, and/or bipolar&#xD;
                  disorder.&#xD;
&#xD;
               4. Current or past hypomanic/manic episode.&#xD;
&#xD;
               5. Current or history of a diagnosis of Attention-Deficit/Hyperactivity Disorder&#xD;
                  (ADHD).&#xD;
&#xD;
          5. Medication&#xD;
&#xD;
               1. Current use, recent discontinuation (within the last month) of any form of&#xD;
                  smoking cessation medications (i.e., Zyban, Wellbutrin, Wellbutrin SR, Chantix,&#xD;
                  nicotine replacement therapy).&#xD;
&#xD;
               2. Current use or recent discontinuation (within the last 60 days) of any of the&#xD;
                  following:&#xD;
&#xD;
                    -  Anti-anxiety or panic disorder medications.&#xD;
&#xD;
                    -  Anti-psychotic medications.&#xD;
&#xD;
                    -  Mood-stabilizers (e.g., Lithium, Lamictal/lamotrigine, Neurontin/gabapentin,&#xD;
                       Topamax/topiramate, valproic acid, Tegretol/carbamazepine).&#xD;
&#xD;
                    -  Anti-depressants (e.g., Wellbutrin, MAOIs, SSRIs, tricyclic&#xD;
                       antidepressants).&#xD;
&#xD;
                    -  Prescription stimulants (e.g., Provigil, Ritalin, Adderall).&#xD;
&#xD;
                    -  Systemic Steroids (e.g., Prednisone).&#xD;
&#xD;
                    -  Alzheimer's disease medications (e.g., Acetylcholinesterase inhibitors&#xD;
                       (ACIs), Aricept/donepezil, Exelon/rivastigmine, Tacrine, or memantine).&#xD;
&#xD;
                    -  Parkinson's disease medications(e.g., Cogentin/benztropine).&#xD;
&#xD;
                    -  Irritable bowel syndrome medication (e.g., Dicylomine/Bentyl).&#xD;
&#xD;
                    -  Heart medications (e.g., quinidine or Procardia/nifedipine).&#xD;
&#xD;
                    -  Peptic ulcer disease medication (e.g, Zantac/ranitidine).&#xD;
&#xD;
                    -  Muscle relaxants (e.g., Soma/carisoprodol, Anectine/succinylcholine).&#xD;
&#xD;
                    -  Anti-fungal medication (e.g., Nizoral/ketoconazole).&#xD;
&#xD;
                    -  Anti-seizure medications (e.g., Ativan, Banzel, Carbatrol, Dilantin,&#xD;
                       Lamictal, Gabitril, Lyrica, Neurontin, Tegretol, Topamax).&#xD;
&#xD;
                    -  COPD medication (e.g., Atrovent/Ipratropium Bromide).&#xD;
&#xD;
                    -  Urinary retention medications (e.g., Duvoid/bethanechol,&#xD;
                       Proscar/finasteride, Avodart/dutasteride, Dibenzyline/phenoxybenzamine,&#xD;
                       Regitine/phentolamine).&#xD;
&#xD;
                    -  Eye medication (e.g., Atropine).&#xD;
&#xD;
               3. Daily use of any of the following:&#xD;
&#xD;
                    -  Opiate-containing medications for chronic pain (Duragesic/fentanyl patches,&#xD;
                       Percocet, Oxycontin).&#xD;
&#xD;
                    -  Medication for asthma (albuterol, Serevent, Combivent, Advair, Flovent,&#xD;
                       Azmacort, Symbicort).&#xD;
&#xD;
               4. Known drug allergy to the study medication.&#xD;
&#xD;
             Subjects will be instructed to refrain from using any study prohibited&#xD;
             drugs/medications (both recreational and prescription) throughout their participation&#xD;
             in the study. After final eligibility is confirmed, subjects who report taking&#xD;
             contraindicated medication(s) over the course of the study period may only remain&#xD;
             eligible if the Study Physician and/or Principal Investigator determines that the&#xD;
             contraindicated medication(s) do/did not impact the study design, data quality, and/or&#xD;
             subject safety/welfare. Subjects are permitted to take necessary prescription&#xD;
             medications not included within the exclusion list during the study.&#xD;
&#xD;
          6. General exclusions&#xD;
&#xD;
               1. Current, anticipated, or pending enrollment in another research program over the&#xD;
                  next 2-3 months that could potentially affect subject safety and/or the study&#xD;
                  data/design as determined by the Principal Investigator and/or Study Physician.&#xD;
&#xD;
               2. Not planning to live in the area for the next two months.&#xD;
&#xD;
               3. Any medical condition, illness, disorder, or concomitant medication that could&#xD;
                  compromise participant safety or treatment, as determined by the Principal&#xD;
                  Investigator and/or Study Physician.&#xD;
&#xD;
               4. Inability to provide informed consent or complete any of the study tasks as&#xD;
                  determined by the Principal Investigator.&#xD;
&#xD;
               5. Completion of neurocognitive assessments and/or use of study medication(s) at the&#xD;
                  CIRNA in the past 6-months that could influence performance on study tasks as&#xD;
                  determined by the Principal Investigator.&#xD;
&#xD;
               6. Not able to effectively communicate in English (reading, writing, speaking).&#xD;
&#xD;
               7. Missing 2 or more consecutive sessions, or 3 or more sessions during the&#xD;
                  medication period.&#xD;
&#xD;
               8. Missing 2 or more consecutive doses during the medication period.&#xD;
&#xD;
               9. Missing 3 or more doses throughout the medication period.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rebecca Ashare, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>August 16, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2012</study_first_posted>
  <results_first_submitted>December 11, 2018</results_first_submitted>
  <results_first_submitted_qc>January 22, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">February 15, 2019</results_first_posted>
  <last_update_submitted>January 22, 2019</last_update_submitted>
  <last_update_submitted_qc>January 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Galantamine</keyword>
  <keyword>Nicotine Bitartrate</keyword>
  <keyword>Nicotine Tartrate</keyword>
  <keyword>Nicotine dependence</keyword>
  <keyword>Tobacco Dependence</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tobacco Use Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Galantamine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 23, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/38/NCT01669538/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Of the 98 subjects who enrolled in the study, 16 were deemed ineligible to participate and therefore not assigned to a treatment arm (i.e., did not Start the study). Thus, 82 subjects Started the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Galantamine</title>
          <description>Galantamine hydrobromide-ER (extended release) is currently marketed for the treatment of Alzheimer's disease. The dosing regimen follows the FDA-approved guidelines. For the first week of study treatment, participants will take 8mg daily of galantamine-ER, preferably with food. 8mg is the lowest dose and this period is designed to introduce the medication into their system. After the initial week, participants will increase their daily dose to 16mg. They will remain on 16mg daily until the end of the treatment period for a total of 23 days on active study medication.&#xD;
Galantamine will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Galantamine</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants assigned to the placebo (sugar pill) arm will take one capsule daily, preferably with food, for a total of 23 days. They will follow the same instructions and complete the same procedures as those in the active treatment.&#xD;
Placebo ingredients (sucrose filler and gel capsules) will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Galantamine</title>
          <description>Galantamine hydrobromide-ER (extended release) is currently marketed for the treatment of Alzheimer's disease. The dosing regimen follows the FDA-approved guidelines. For the first week of study treatment, participants will take 8mg daily of galantamine-ER, preferably with food. 8mg is the lowest dose and this period is designed to introduce the medication into their system. After the initial week, participants will increase their daily dose to 16mg. They will remain on 16mg daily until the end of the treatment period for a total of 23 days on active study medication.&#xD;
Galantamine will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Galantamine</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants assigned to the placebo (sugar pill) arm will take one capsule daily, preferably with food, for a total of 23 days. They will follow the same instructions and complete the same procedures as those in the active treatment.&#xD;
Placebo ingredients (sucrose filler and gel capsules) will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Placebo</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="40"/>
            <count group_id="B2" value="42"/>
            <count group_id="B3" value="82"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="42.9" spread="11.3"/>
                    <measurement group_id="B2" value="42.8" spread="10.9"/>
                    <measurement group_id="B3" value="42.8" spread="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="78"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Nicotine Dependence</title>
          <description>Self-report measure of nicotine dependence on a scale from 0 to 10 with 0 being not at all dependent and 10 being highly dependent.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.1" spread="1.5"/>
                    <measurement group_id="B2" value="5.4" spread="1.8"/>
                    <measurement group_id="B3" value="5.2" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cigarettes per day</title>
          <units>cigarettes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15.2" spread="4.7"/>
                    <measurement group_id="B2" value="15.5" spread="6.9"/>
                    <measurement group_id="B3" value="15.4" spread="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Total Number of Smoke-free Days (Biochemically Verified) During a 7-day Quit Attempt.</title>
        <description>Day 17 will be the beginning of a 7-day quit attempt, during which the total number of days of abstinence will be assessed.</description>
        <time_frame>Days 17-23</time_frame>
        <population>Number of subjects who completed the study in each arm</population>
        <group_list>
          <group group_id="O1">
            <title>Galantamine</title>
            <description>Galantamine hydrobromide-ER (extended release) is currently marketed for the treatment of Alzheimer's disease. The dosing regimen follows the FDA-approved guidelines. For the first week of study treatment, participants will take 8mg daily of galantamine-ER, preferably with food. 8mg is the lowest dose and this period is designed to introduce the medication into their system. After the initial week, participants will increase their daily dose to 16mg. They will remain on 16mg daily until the end of the treatment period for a total of 23 days on active study medication.&#xD;
Galantamine will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Galantamine</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to the placebo (sugar pill) arm will take one capsule daily, preferably with food, for a total of 23 days. They will follow the same instructions and complete the same procedures as those in the active treatment.&#xD;
Placebo ingredients (sucrose filler and gel capsules) will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of Smoke-free Days (Biochemically Verified) During a 7-day Quit Attempt.</title>
          <description>Day 17 will be the beginning of a 7-day quit attempt, during which the total number of days of abstinence will be assessed.</description>
          <population>Number of subjects who completed the study in each arm</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6" spread="2.3"/>
                    <measurement group_id="O2" value="3.7" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Performance</title>
        <description>Participants will complete neurocognitive tests designed to test working memory and attention. These tests are similar to computer games, in that participants will push a button in response to the pictures they see.</description>
        <time_frame>Baseline (Day 0), Day 14 (day before start of 24-hour abstinence period), Day 16 (after 24-hour abstinence period ends)</time_frame>
        <population>Number of subjects who completed the study in each arm</population>
        <group_list>
          <group group_id="O1">
            <title>Galantamine</title>
            <description>Galantamine hydrobromide-ER (extended release) is currently marketed for the treatment of Alzheimer's disease. The dosing regimen follows the FDA-approved guidelines. For the first week of study treatment, participants will take 8mg daily of galantamine-ER, preferably with food. 8mg is the lowest dose and this period is designed to introduce the medication into their system. After the initial week, participants will increase their daily dose to 16mg. They will remain on 16mg daily until the end of the treatment period for a total of 23 days on active study medication.&#xD;
Galantamine will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Galantamine</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to the placebo (sugar pill) arm will take one capsule daily, preferably with food, for a total of 23 days. They will follow the same instructions and complete the same procedures as those in the active treatment.&#xD;
Placebo ingredients (sucrose filler and gel capsules) will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Performance</title>
          <description>Participants will complete neurocognitive tests designed to test working memory and attention. These tests are similar to computer games, in that participants will push a button in response to the pictures they see.</description>
          <population>Number of subjects who completed the study in each arm</population>
          <units>number of correct responses</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Working memory (Baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.3" spread="5.0"/>
                    <measurement group_id="O2" value="46.6" spread="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Working memory (Day 14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.0" spread="4.6"/>
                    <measurement group_id="O2" value="48.4" spread="5.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Working memory (Day 16)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.3" spread="7.0"/>
                    <measurement group_id="O2" value="47.1" spread="6.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Attention (Baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="111.3" spread="8.9"/>
                    <measurement group_id="O2" value="103.4" spread="20.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Attention (Day 14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="113.9" spread="8.3"/>
                    <measurement group_id="O2" value="110.5" spread="11.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Attention (Day 16)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="115.2" spread="6.4"/>
                    <measurement group_id="O2" value="111.0" spread="11.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Subjective Symptoms</title>
        <description>Smoking urges [Questionnaire of Smoking Urges-Brief; QSU-B; 10-items rated on a 7-point scale (1=strongly disagree, 7=strongly agree) and summed for total score (range: 10-70). Higher scores=greater urge to smoke.] Negative mood [Negative Affect scale (10 items) from the Positive and Negative Affect Schedule; PANAS; 20-item Likert-format measure; The subscale was summed to create a summary score (range: 10-50); Lower negative affect indicates better outcomes.] Nicotine withdrawal [Minnesota Nicotine Withdrawal Scale-Revised; MNWS-R; 15 symptoms are rated on intensity with the following scale: 0=none, 1=slight, 2=mild, 3=moderate, 4=severe. The first 9 items are summed for total score (range: 0-36); higher scores=more severe withdrawal.].&#xD;
Measures assessed at the following visits: Baseline; Day 7 (monitoring visit); Day 14 (Day before 24-hour abstinence period), Day 16 (after 24-hour abstinence period), and Days 17-23 (7-day quit attempt).</description>
        <time_frame>Baseline (day 0), Days 7, 14, 16, 17, 19, 21, and 23</time_frame>
        <population>Number of subjects who completed the study in each arm</population>
        <group_list>
          <group group_id="O1">
            <title>Galantamine</title>
            <description>Galantamine hydrobromide-ER (extended release) is currently marketed for the treatment of Alzheimer's disease. The dosing regimen follows the FDA-approved guidelines. For the first week of study treatment, participants will take 8mg daily of galantamine-ER, preferably with food. 8mg is the lowest dose and this period is designed to introduce the medication into their system. After the initial week, participants will increase their daily dose to 16mg. They will remain on 16mg daily until the end of the treatment period for a total of 23 days on active study medication.&#xD;
Galantamine will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Galantamine</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to the placebo (sugar pill) arm will take one capsule daily, preferably with food, for a total of 23 days. They will follow the same instructions and complete the same procedures as those in the active treatment.&#xD;
Placebo ingredients (sucrose filler and gel capsules) will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Subjective Symptoms</title>
          <description>Smoking urges [Questionnaire of Smoking Urges-Brief; QSU-B; 10-items rated on a 7-point scale (1=strongly disagree, 7=strongly agree) and summed for total score (range: 10-70). Higher scores=greater urge to smoke.] Negative mood [Negative Affect scale (10 items) from the Positive and Negative Affect Schedule; PANAS; 20-item Likert-format measure; The subscale was summed to create a summary score (range: 10-50); Lower negative affect indicates better outcomes.] Nicotine withdrawal [Minnesota Nicotine Withdrawal Scale-Revised; MNWS-R; 15 symptoms are rated on intensity with the following scale: 0=none, 1=slight, 2=mild, 3=moderate, 4=severe. The first 9 items are summed for total score (range: 0-36); higher scores=more severe withdrawal.].&#xD;
Measures assessed at the following visits: Baseline; Day 7 (monitoring visit); Day 14 (Day before 24-hour abstinence period), Day 16 (after 24-hour abstinence period), and Days 17-23 (7-day quit attempt).</description>
          <population>Number of subjects who completed the study in each arm</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Smoking urges (baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.4" spread="13"/>
                    <measurement group_id="O2" value="30.2" spread="14.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smoking urges (day 7)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.6" spread="9.8"/>
                    <measurement group_id="O2" value="25.9" spread="15.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smoking urges (day 14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.1" spread="13.2"/>
                    <measurement group_id="O2" value="24.1" spread="12.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smoking urges (day 16)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33" spread="15.6"/>
                    <measurement group_id="O2" value="36" spread="17.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smoking urges (day 17)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.7" spread="9.9"/>
                    <measurement group_id="O2" value="29.7" spread="17.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smoking urges (day 19)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.7" spread="11.8"/>
                    <measurement group_id="O2" value="25.2" spread="14.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smoking urges (day 21)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.8" spread="9.6"/>
                    <measurement group_id="O2" value="22.2" spread="12.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Smoking urges (day 23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.8" spread="8.6"/>
                    <measurement group_id="O2" value="23.2" spread="14.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative Mood (baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.2" spread="2.9"/>
                    <measurement group_id="O2" value="12.7" spread="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative Mood (day 7)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.2" spread="2.6"/>
                    <measurement group_id="O2" value="12.0" spread="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative Mood (day 14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.8" spread="3.5"/>
                    <measurement group_id="O2" value="11.9" spread="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative Mood (day 16)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.7" spread="5.7"/>
                    <measurement group_id="O2" value="13.9" spread="4.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative Mood (day 17)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" spread="3.5"/>
                    <measurement group_id="O2" value="11.7" spread="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative Mood (day 19)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" spread="2.9"/>
                    <measurement group_id="O2" value="12.0" spread="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative Mood (day 21)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.0" spread="3.6"/>
                    <measurement group_id="O2" value="11.8" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative Mood (day 23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.1" spread="2.5"/>
                    <measurement group_id="O2" value="12.0" spread="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Withdrawal (baseline)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" spread="2.8"/>
                    <measurement group_id="O2" value="5.6" spread="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Withdrawal (day 7)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="2.3"/>
                    <measurement group_id="O2" value="5.4" spread="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Withdrawal (day 14)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" spread="3.8"/>
                    <measurement group_id="O2" value="3.9" spread="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Withdrawal (day 16)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.6" spread="6.2"/>
                    <measurement group_id="O2" value="7.7" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Withdrawal (day 17)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="4.4"/>
                    <measurement group_id="O2" value="4.6" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Withdrawal (day 19)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" spread="4"/>
                    <measurement group_id="O2" value="4.6" spread="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Withdrawal (day 21)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" spread="3.5"/>
                    <measurement group_id="O2" value="4.8" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Withdrawal (day 23)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.2" spread="3.5"/>
                    <measurement group_id="O2" value="4.1" spread="5.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Common Side Effects of Galantamine Check List</title>
        <description>Subjects completed a side effect checklist at every in-person study visit over the course of the treatment period. Subjects rated the severity of 37 common side effects of galantamine on the following scale: 0=none, 1=mild, 2=moderate, 3=severe. The average of all items was used to create a summary side effect score (range for total summary score 0-3). Higher scores indicate greater severity of side effects.&#xD;
Side effects of galantamine were assessed at the following in-person sessions: Baseline session; Day 7 (brief monitoring visit); Day 14 (Day before 24-hour abstinence period), Day 16 (after 24-hour abstinence period), and Days 17-23 (during the 7-day quit attempt).</description>
        <time_frame>Baseline (day 0), Days 7, 14, 16, 17, 19, 21, and 23</time_frame>
        <population>Number of subjects who completed the study in each arm</population>
        <group_list>
          <group group_id="O1">
            <title>Galantamine</title>
            <description>Galantamine hydrobromide-ER (extended release) is currently marketed for the treatment of Alzheimer's disease. The dosing regimen follows the FDA-approved guidelines. For the first week of study treatment, participants will take 8mg daily of galantamine-ER, preferably with food. 8mg is the lowest dose and this period is designed to introduce the medication into their system. After the initial week, participants will increase their daily dose to 16mg. They will remain on 16mg daily until the end of the treatment period for a total of 23 days on active study medication.&#xD;
Galantamine will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Galantamine</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to the placebo (sugar pill) arm will take one capsule daily, preferably with food, for a total of 23 days. They will follow the same instructions and complete the same procedures as those in the active treatment.&#xD;
Placebo ingredients (sucrose filler and gel capsules) will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Common Side Effects of Galantamine Check List</title>
          <description>Subjects completed a side effect checklist at every in-person study visit over the course of the treatment period. Subjects rated the severity of 37 common side effects of galantamine on the following scale: 0=none, 1=mild, 2=moderate, 3=severe. The average of all items was used to create a summary side effect score (range for total summary score 0-3). Higher scores indicate greater severity of side effects.&#xD;
Side effects of galantamine were assessed at the following in-person sessions: Baseline session; Day 7 (brief monitoring visit); Day 14 (Day before 24-hour abstinence period), Day 16 (after 24-hour abstinence period), and Days 17-23 (during the 7-day quit attempt).</description>
          <population>Number of subjects who completed the study in each arm</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".03" spread=".06"/>
                    <measurement group_id="O2" value=".04" spread=".07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".09" spread=".09"/>
                    <measurement group_id="O2" value=".07" spread=".08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".1" spread=".15"/>
                    <measurement group_id="O2" value=".06" spread=".11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 16</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".1" spread=".12"/>
                    <measurement group_id="O2" value=".08" spread=".1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 17</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".08" spread=".12"/>
                    <measurement group_id="O2" value=".05" spread=".08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 19</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".07" spread=".09"/>
                    <measurement group_id="O2" value=".05" spread=".09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".06" spread=".08"/>
                    <measurement group_id="O2" value=".05" spread=".08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 23</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".05" spread=".06"/>
                    <measurement group_id="O2" value=".05" spread=".08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>23 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Galantamine</title>
          <description>Galantamine hydrobromide-ER (extended release) is currently marketed for the treatment of Alzheimer's disease. The dosing regimen follows the FDA-approved guidelines. For the first week of study treatment, participants will take 8mg daily of galantamine-ER, preferably with food. 8mg is the lowest dose and this period is designed to introduce the medication into their system. After the initial week, participants will increase their daily dose to 16mg. They will remain on 16mg daily until the end of the treatment period for a total of 23 days on active study medication.&#xD;
Galantamine will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Galantamine</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants assigned to the placebo (sugar pill) arm will take one capsule daily, preferably with food, for a total of 23 days. They will follow the same instructions and complete the same procedures as those in the active treatment.&#xD;
Placebo ingredients (sucrose filler and gel capsules) will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.&#xD;
Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Difficulty sleeping</sub_title>
                <counts group_id="E1" events="10" subjects_affected="4" subjects_at_risk="40"/>
                <counts group_id="E2" events="6" subjects_affected="3" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Rebecca Ashare</name_or_title>
      <organization>University of Pennsylvania</organization>
      <phone>2157465789</phone>
      <email>rlashare@pennmedicine.upenn.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01669538
org study id: 815789
secondary id: UPCC15912
secondary id: K23DA035295
nct id: NCT01669538
nct alias: NCT01845961
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
This is a randomized, double-blind, placebo-controlled study to test whether a medication
      called galantamine (Brand Name: Razadyne) will help smokers quit and whether it reduces
      cognitive problems that smokers experience during a quit attempt.
Galantamine, an FDA-approved treatment for Alzheimer's disease, is used to treat cognitive
      impairment by enhancing acetylcholine through inhibition of the enzyme, acetylcholinesterase.
      We propose randomized double-blind placebo-controlled study of short-term (23 days) treatment
      with galantamine.

      Eighty chronic smokers will complete a validated procedure for screening new medications. An
      equal number of subjects will be assigned to one of two groups: galantamine-ER or placebo.
      Participants in both groups will take one capsule each day and follow the same procedures.
      This is not a cross-over trial.

      For participants in the galantamine group, following an initial 1-week drug run-up phase (8mg
      daily of galantamine-ER), the medication dose will be increased to 16mg daily of
      galantamine-ER for the remainder of the study (up to Day 23).

      On Day 15, smokers will begin a mandatory 24-hour abstinence period, which will be followed
      by a programmed smoking lapse on Day 16. Smokers will then be instructed to abstain for the
      following 7 days (observed abstinence). Following completion of the study, participants will
      be offered standard smoking cessation treatment.

      On Days 0 (Baseline), 14, and 16, subjects will perform the following computer tasks: a
      working memory task (Visual/Spatial N-Back), sustained attention tasks (Penn Continuous
      Performance Task [PCPT-nl] and XO Reaction Time Task), a recall memory task (Word
      Recognition), an interference control task (Stroop test), and a response inhibition task
      (Stop Signal Task).

      The primary outcome is to identify changes in behavioral performance and subjective symptoms
      following two weeks treatment of galantamine and after 24 hours of abstinence, compared to
      baseline.

      This study will provide information about the role of the cholinergic system during brief
      abstinence and whether enhancing acetylcholine reduces abstinence-induced cognitive symptoms
      that promote smoking relapse. Information obtained in this study may further establish
      cognitive performance measures as endophenotypes for nicotine dependence.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Total Number of Smoke-free Days (Biochemically Verified) During a 7-day Quit Attempt.
time frame: Days 17-23
description: Day 17 will be the beginning of a 7-day quit attempt, during which the total number of days of abstinence will be assessed.
measure: Cognitive Performance
time frame: Baseline (Day 0), Day 14 (day before start of 24-hour abstinence period), Day 16 (after 24-hour abstinence period ends)
description: Participants will complete neurocognitive tests designed to test working memory and attention. These tests are similar to computer games, in that participants will push a button in response to the pictures they see.
measure: Subjective Symptoms
time frame: Baseline (day 0), Days 7, 14, 16, 17, 19, 21, and 23
description: Smoking urges [Questionnaire of Smoking Urges-Brief; QSU-B; 10-items rated on a 7-point scale (1=strongly disagree, 7=strongly agree) and summed for total score (range: 10-70). Higher scores=greater urge to smoke.] Negative mood [Negative Affect scale (10 items) from the Positive and Negative Affect Schedule; PANAS; 20-item Likert-format measure; The subscale was summed to create a summary score (range: 10-50); Lower negative affect indicates better outcomes.] Nicotine withdrawal [Minnesota Nicotine Withdrawal Scale-Revised; MNWS-R; 15 symptoms are rated on intensity with the following scale: 0=none, 1=slight, 2=mild, 3=moderate, 4=severe. The first 9 items are summed for total score (range: 0-36); higher scores=more severe withdrawal.].
Measures assessed at the following visits: Baseline; Day 7 (monitoring visit); Day 14 (Day before 24-hour abstinence period), Day 16 (after 24-hour abstinence period), and Days 17-23 (7-day quit attempt).
measure: Common Side Effects of Galantamine Check List
time frame: Baseline (day 0), Days 7, 14, 16, 17, 19, 21, and 23
description: Subjects completed a side effect checklist at every in-person study visit over the course of the treatment period. Subjects rated the severity of 37 common side effects of galantamine on the following scale: 0=none, 1=mild, 2=moderate, 3=severe. The average of all items was used to create a summary side effect score (range for total summary score 0-3). Higher scores indicate greater severity of side effects.
Side effects of galantamine were assessed at the following in-person sessions: Baseline session; Day 7 (brief monitoring visit); Day 14 (Day before 24-hour abstinence period), Day 16 (after 24-hour abstinence period), and Days 17-23 (during the 7-day quit attempt).
arm group label: Galantamine
arm group type: Experimental
description: Galantamine hydrobromide-ER (extended release) is currently marketed for the treatment of Alzheimer's disease. The dosing regimen follows the FDA-approved guidelines. For the first week of study treatment, participants will take 8mg daily of galantamine-ER, preferably with food. 8mg is the lowest dose and this period is designed to introduce the medication into their system. After the initial week, participants will increase their daily dose to 16mg. They will remain on 16mg daily until the end of the treatment period for a total of 23 days on active study medication.
Galantamine will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants assigned to the placebo (sugar pill) arm will take one capsule daily, preferably with food, for a total of 23 days. They will follow the same instructions and complete the same procedures as those in the active treatment.
Placebo ingredients (sucrose filler and gel capsules) will be purchased, encapsulated, and packaged into blister packs by the Investigational Drug Service at the University of Pennsylvania. Both active medication and placebo will look identical.
intervention type: Drug
intervention name: Galantamine
arm group label: Galantamine
other name: Galantamine hydrobromide ER
other name: Razadyne ER
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
other name: Sugar pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Rebecca Ashare, Ph.D.
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tobacco Use Disorder
mesh term: Galantamine
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 