<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/NCT03774810</url>
  </required_header>
  <id_info>
    <org_study_id>831801</org_study_id>
    <secondary_id>R01AG054521-01A1</secondary_id>
    <nct_id>NCT03774810</nct_id>
  </id_info>
  <brief_title>Partial Reinforcement II: Three Approaches to Maintenance Therapy for Chronic Insomnia</brief_title>
  <acronym>R01</acronym>
  <official_title>Three Approaches to Maintenance Therapy for Chronic Insomnia in Older Adults</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 Institute on Aging (NIA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is a three phase sequential study of the medical treatment of insomnia with&#xD;
      zolpidem. All participating subjects will receive one month of standard nightly treatment. If&#xD;
      the subject has a positive treatment response they continue in the study and are randomized&#xD;
      to one of four conditions: intermittent dosing (3-5 pills week, full dose), or one of three&#xD;
      variable dose conditions (nightly pill use where any given pill is a variable dose). Standard&#xD;
      treatment will last for 4 weeks. The experimental phase will extend over two periods. The&#xD;
      first period will last for 12 weeks. The second period will last for 36 weeks. Both periods&#xD;
      include:&#xD;
&#xD;
      • Taking a pill 30 minutes prior to bedtime.&#xD;
&#xD;
      In one case, this will involve taking 3-5 pills per week. In the remaining condition pills&#xD;
      will be taken on each and every night. Depending on the specific group that the subject is&#xD;
      assigned to, they will either receive 10mg or 5mg of zolpidem (variable by age and sex) or a&#xD;
      variable dose of zolpidem on a nightly basis (range from 0 mg to 10 mg per night).&#xD;
&#xD;
        -  Completing a sleep diary each day;&#xD;
&#xD;
        -  Completing 6 to 7 questionnaires each week;&#xD;
&#xD;
        -  A monthly visit to Penn to return your medication foil packs and to receive a new foil&#xD;
           pack with the next month of medication.&#xD;
&#xD;
      During Phases 3&amp;4, the subject will be asked to undergo quarter annual physicals so that we&#xD;
      can optimally track their health and wellbeing. The physicals will involve standard vitals&#xD;
      measures (e.g., temperature, blood pressure, height and weight, etc.) and, based on the&#xD;
      judgement of the research clinician, may involve an EKG and blood and urine chemistries.&#xD;
&#xD;
      If the subject does not experience a treatment response or (following a treatment response)&#xD;
      experiences a relapse of insomnia, they will not continue in the study but will be given the&#xD;
      opportunity to be treated with Cognitive Behavioral Therapy for Insomnia (CBT-I) at no cost.&#xD;
      Assessments of the subjects clinical status will be based on your daily sleep diaries and&#xD;
      weekly questionnaires.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phase-1: Initial Evaluation.&#xD;
&#xD;
      This evaluation occurs at the offices of the Behavioral Sleep Medicine Program (Suite 670,&#xD;
      3535 Market Street Philadelphia, PA 19104) and lasts about 1 to 2 hours. Procedures include:&#xD;
&#xD;
        -  Completing forms asking questions about your sleep, mood, alcohol use, medical history,&#xD;
           your current medications, and background questions about your age, race, and education.&#xD;
&#xD;
        -  The provision of your consent to contact your primary care provider to gain their assent&#xD;
           (agreement) that you may participate in the trial safely.&#xD;
&#xD;
      The information obtained during the initial assessment will be used to see if you are&#xD;
      eligible to participate in this study. If you are determined ineligible, you will not be able&#xD;
      to continue in the study but will be provided with a referral if appropriate.&#xD;
&#xD;
      NOTE: This study will be using an Internet Data Portal (IDP) system to collect most&#xD;
      questionnaire data. The IDP is a Research Electronic Data Capture and is a secure web&#xD;
      application. It is a password protected site located on Penn's servers in which the data will&#xD;
      live in a database online where only qualified research personnel can access it. During the&#xD;
      initial evaluation you will be introduced to this system and provided with a username and&#xD;
      password. The study staff will assist you in filling out the questionnaires using this IDP&#xD;
      system.&#xD;
&#xD;
      Phase-2: Baseline Period.&#xD;
&#xD;
      This phase lasts 14 days. Your participation includes:&#xD;
&#xD;
        -  Completing daily sleep diaries at home. The online diary form requires about 5 minutes&#xD;
           each day to complete.&#xD;
&#xD;
        -  Completing 6 to 7 forms asking questions about your medical symptoms, and sleep each&#xD;
           week of the baseline period. These online questionnaires require about 15 minutes to&#xD;
           complete.&#xD;
&#xD;
        -  Abstaining from the use of any medication or over the counter product that is used&#xD;
           expressly for the purpose of helping you fall or stay asleep (e.g. trazadone/Desyrel,&#xD;
           melatonin, Nyquil, Tylenol PM, Benadryl, etc.). If you choose to discontinue your&#xD;
           current sleep medication to participate in our study, please do this in consultation&#xD;
           with the clinician that prescribed your sleep medication. Please note that&#xD;
           discontinuation of your current sleep medication will make it necessary to extend the&#xD;
           baseline component of our study by at least two weeks. Should the sleep diaries indicate&#xD;
           that your insomnia is not of the type, severity, or frequency required for the study,&#xD;
           you will not be able to continue in the study but will be provided with a referral. This&#xD;
           referral will be for the Penn Sleep Disorder Center. If you or study personnel deem your&#xD;
           two weeks to be unusual, you may be offered the chance to repeat the baseline period.&#xD;
&#xD;
      Phase-3: Sleep Lab Study (polysomnography) or Home Sleep Apnea Test (HSAT). You will undergo&#xD;
      a polysomnography study or an HSAT to determine if you are eligible to continue in the study.&#xD;
      During the pandemic all sleep tests will be administered at home. After the pandemic, the&#xD;
      study investigators will decide which type of study you will receive. Both sleep assessments&#xD;
      will last for 1 night.&#xD;
&#xD;
      The HSAT equipment will be shipped to your house. A member of the study team will contact you&#xD;
      to go over proper use instructions. On the night of the test, you can go to bed at your&#xD;
      regular bedtime. Prior to bedtime, you will attach the sensor(s) as instructed and start the&#xD;
      test. Upon waking up, you will stop the test and remove the sensor(s). On the day immediately&#xD;
      following the sleep test, you will ship the device back in the prepaid shipping envelope&#xD;
      Procedures for the polysomnography study are: you will be asked to arrive at the sleep lab&#xD;
      located at the Hospital of the University of Pennsylvania (HUP) at the cross streets of 34th&#xD;
      and Spruce by 7 P.M. for a polysomnographic study (PSG). Upon arrival, to ensure for accurate&#xD;
      laboratory measurements, urine toxicology screens may be performed to rule out illegal&#xD;
      substance use. These data are acquired to explain abnormal findings on the PSG. Following the&#xD;
      sleep study, it will be determined whether a repeat study is necessary based on the findings&#xD;
      both from the clinical chemistries and the polysomnography. If a repeat study is necessary,&#xD;
      one of the project investigators will discuss the issue of substance use with you to: (1)&#xD;
      determine if the clinical chemistries' finding was an error (for example poppy seeds led to a&#xD;
      positive screen) or (2) gain your willingness to refrain from substance use for the second&#xD;
      PSG and for the remainder of the study. If you screen positive a second time, your&#xD;
      participation will be discontinued.&#xD;
&#xD;
      The specific procedure for a PSG requires that you have a set of sensors placed on your face,&#xD;
      scalp, and body by a technician. All the sensors are attached with surgical tape, paste and&#xD;
      glue. The sensors on your face are attached on your left and right temple, cheek bone and&#xD;
      under your nose. The sensors on the temple and cheek bone measure eye movements associated&#xD;
      with falling asleep and dreaming. The sensors under your nose measure airflow through your&#xD;
      mouth and nose. The sensors on your scalp measure brain waves during sleep. The sensors on&#xD;
      the body are placed above the collar bones and over the calf muscles. The sensors over the&#xD;
      collar bones measure heart muscle activity. The sensors over the calf muscles measure muscle&#xD;
      activity from the legs. In addition, a strap will be placed around your chest and abdomen to&#xD;
      measure respiration.&#xD;
&#xD;
      After you have been connected to the equipment, you are expected to stay in bed until final&#xD;
      wake time the next morning, except for bathroom breaks. You will be visually monitored by the&#xD;
      lab technicians by remote video. In the morning, you will be awakened by the technician (if&#xD;
      needed), be unhooked from the equipment, and then allowed to shower, dress, and eat before&#xD;
      leaving. You will be free to go about your normal schedule for the rest of the day.&#xD;
&#xD;
      If the in-lab PSG sleep or HSAT study finds evidence of a sleep disorder other than insomnia,&#xD;
      such as sleep apnea, you will not be able to continue in the study but will be provided with&#xD;
      a referral.&#xD;
&#xD;
      Phase-4: Standard Treatment. All participating subjects will receive one month of standard&#xD;
      nightly treatment. If you have a positive treatment response you will remain in the study and&#xD;
      be randomized to one of the following treatment conditions: nightly dosing, intermittent&#xD;
      dosing (1-3 pills week, full dose), or one of two variable dose conditions (nightly pill use&#xD;
      where any given pill is a variable dose). The assignment of condition will be accomplished by&#xD;
      a process that is the same as the flip of a coin and neither you nor the study personnel will&#xD;
      know which condition you have been assigned to (this is referred to as a &quot;double blind&quot;&#xD;
      study). You will have an equal chance of being randomized to each of the 4 study arms. In the&#xD;
      case of an emergency, the blind will be broken and the study doctor and clinicians associated&#xD;
      with your care will be informed of which dosing condition you were assigned to.&#xD;
&#xD;
      Standard treatment will last for 4 weeks. The experimental phase will extend over two&#xD;
      periods. The first period will last for 12 weeks. The second period will last for 36 weeks.&#xD;
&#xD;
      Both periods include:&#xD;
&#xD;
        -  Taking a pill 30 minutes prior to bedtime. In one case, this will involve taking 1-3&#xD;
           pills per week. In the remaining conditions, pills will be taken on each and every&#xD;
           night. Depending on the specific group you are assigned to, you will either receive 10mg&#xD;
           or 5mg of zolpidem (variable by age and sex) or a variable dose of zolpidem on a nightly&#xD;
           basis (range from 0 mg to 10 mg per night). Please note that the effect of zolpidem may&#xD;
           be slowed if taken with or immediately after a meal.&#xD;
&#xD;
        -  Completing a sleep diary each day;&#xD;
&#xD;
        -  Completing 6 to 7 questionnaires each week;&#xD;
&#xD;
        -  A monthly visit to Penn to return your medication foil packs and to receive a new foil&#xD;
           pack with the next month of medication.&#xD;
&#xD;
      If you do not experience a treatment response or (following a treatment response) you&#xD;
      experience a relapse of insomnia, you will not be able to continue in the study but will be&#xD;
      given the opportunity to be treated with Cognitive Behavioral Therapy for Insomnia (CBT-I) at&#xD;
      no cost. Assessments of your clinical status (how your insomnia is responding to treatment)&#xD;
      will be based on your daily sleep diaries and weekly questionnaires.&#xD;
&#xD;
      During Phase-4, you will be asked to undergo quarter annual physicals so that we can&#xD;
      optimally track your health and wellbeing. The physicals will involve standard vital measures&#xD;
      (e.g., temperature, blood pressure, height and weight, etc.) and, based on the judgement of&#xD;
      the research clinician, may involve an EKG and/or blood and urine chemistries.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 15, 2019</start_date>
  <completion_date type="Actual">June 30, 2023</completion_date>
  <primary_completion_date type="Actual">June 30, 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double Blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Insomnia Relapse</measure>
    <time_frame>1 year</time_frame>
    <description>Tracking Relapse via assessing daily sleep diary responses.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sleep Continuity</measure>
    <time_frame>1 year</time_frame>
    <description>Assess sleep continuity by assessing daily sleep diary responses.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">198</enrollment>
  <condition>Insomnia</condition>
  <condition>Insomnia Chronic</condition>
  <arm_group>
    <arm_group_label>Continuous</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nightly active dose (QHS). The intervention is zolpidem tartrate 5 mg or 10 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Partial Reinforcement 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 active dose per week with 6 placebos interspersed between the active dose. The intervention is zolpidem tartrate 5 mg or 10 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Partial Reinforcement 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 active doses per week with 4 placebos interspersed between the active doses. The intervention is zolpidem tartrate 5 mg or 10 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Frequency Intermittent Dosing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 to 3 active doses per week PRN. The intervention is zolpidem tartrate 5 mg or 10 mg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zolpidem tartrate</intervention_name>
    <description>Zolpidem Tartrate, 5mg for men older than 60 and women of all ages. 10 mg for men younger than 60.</description>
    <arm_group_label>Continuous</arm_group_label>
    <arm_group_label>Low Frequency Intermittent Dosing</arm_group_label>
    <arm_group_label>Partial Reinforcement 1</arm_group_label>
    <arm_group_label>Partial Reinforcement 3</arm_group_label>
    <other_name>zolpidem</other_name>
    <other_name>ambien</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with chronic insomnia will meet DSM-5 criteria for Insomnia Disorder, ICSD-3,&#xD;
             and RDC criteria for Psychophysiologic Insomnia. In addition, all subjects will have a&#xD;
             sleep initiation and/or a sleep maintenance complaint (&gt; 30 min. to fall asleep and/or&#xD;
             &gt; 30 min. of wakefulness during the night) with a problem frequency &gt; 3 nights/wk and&#xD;
             problem duration &gt; 3 mo. This profile must be evident at both intake (based on&#xD;
             retrospective reports) and as an average profile from the two weeks of baseline&#xD;
             diaries (prospective sampling).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  currently in treatment for insomnia, unstable medical or psychiatric illness, a&#xD;
             history of treatment failure with zolpidem, discontinuation of zolpidem owing to side&#xD;
             effects, and/or current experience, or history, of parasomnias (within the last 5&#xD;
             years).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael L Perlis, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>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>
  <link>
    <url>http://www.sleeplessinphilly.com</url>
    <description>Click here to learn about our available studies</description>
  </link>
  <link>
    <url>http://www.med.upenn.edu/bsm/</url>
    <description>Click here to learn more about our sleep research laboratory</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 13, 2018</study_first_posted>
  <last_update_submitted>July 18, 2023</last_update_submitted>
  <last_update_submitted_qc>July 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>insomnia</keyword>
  <keyword>sleep</keyword>
  <keyword>chronic insomnia</keyword>
  <keyword>zolpidem</keyword>
  <keyword>ambien</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Initiation and Maintenance Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Zolpidem</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 1, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/10/NCT03774810/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 1, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/10/NCT03774810/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03774810
org study id: 831801
secondary id: R01AG054521-01A1
nct id: NCT03774810
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The study is a three phase sequential study of the medical treatment of insomnia with
      zolpidem. All participating subjects will receive one month of standard nightly treatment. If
      the subject has a positive treatment response they continue in the study and are randomized
      to one of four conditions: intermittent dosing (3-5 pills week, full dose), or one of three
      variable dose conditions (nightly pill use where any given pill is a variable dose). Standard
      treatment will last for 4 weeks. The experimental phase will extend over two periods. The
      first period will last for 12 weeks. The second period will last for 36 weeks. Both periods
      include:

      • Taking a pill 30 minutes prior to bedtime.

      In one case, this will involve taking 3-5 pills per week. In the remaining condition pills
      will be taken on each and every night. Depending on the specific group that the subject is
      assigned to, they will either receive 10mg or 5mg of zolpidem (variable by age and sex) or a
      variable dose of zolpidem on a nightly basis (range from 0 mg to 10 mg per night).

        -  Completing a sleep diary each day;

        -  Completing 6 to 7 questionnaires each week;

        -  A monthly visit to Penn to return your medication foil packs and to receive a new foil
           pack with the next month of medication.

      During Phases 3&4, the subject will be asked to undergo quarter annual physicals so that we
      can optimally track their health and wellbeing. The physicals will involve standard vitals
      measures (e.g., temperature, blood pressure, height and weight, etc.) and, based on the
      judgement of the research clinician, may involve an EKG and blood and urine chemistries.

      If the subject does not experience a treatment response or (following a treatment response)
      experiences a relapse of insomnia, they will not continue in the study but will be given the
      opportunity to be treated with Cognitive Behavioral Therapy for Insomnia (CBT-I) at no cost.
      Assessments of the subjects clinical status will be based on your daily sleep diaries and
      weekly questionnaires.
Phase-1: Initial Evaluation.

      This evaluation occurs at the offices of the Behavioral Sleep Medicine Program (Suite 670,
      3535 Market Street Philadelphia, PA 19104) and lasts about 1 to 2 hours. Procedures include:

        -  Completing forms asking questions about your sleep, mood, alcohol use, medical history,
           your current medications, and background questions about your age, race, and education.

        -  The provision of your consent to contact your primary care provider to gain their assent
           (agreement) that you may participate in the trial safely.

      The information obtained during the initial assessment will be used to see if you are
      eligible to participate in this study. If you are determined ineligible, you will not be able
      to continue in the study but will be provided with a referral if appropriate.

      NOTE: This study will be using an Internet Data Portal (IDP) system to collect most
      questionnaire data. The IDP is a Research Electronic Data Capture and is a secure web
      application. It is a password protected site located on Penn's servers in which the data will
      live in a database online where only qualified research personnel can access it. During the
      initial evaluation you will be introduced to this system and provided with a username and
      password. The study staff will assist you in filling out the questionnaires using this IDP
      system.

      Phase-2: Baseline Period.

      This phase lasts 14 days. Your participation includes:

        -  Completing daily sleep diaries at home. The online diary form requires about 5 minutes
           each day to complete.

        -  Completing 6 to 7 forms asking questions about your medical symptoms, and sleep each
           week of the baseline period. These online questionnaires require about 15 minutes to
           complete.

        -  Abstaining from the use of any medication or over the counter product that is used
           expressly for the purpose of helping you fall or stay asleep (e.g. trazadone/Desyrel,
           melatonin, Nyquil, Tylenol PM, Benadryl, etc.). If you choose to discontinue your
           current sleep medication to participate in our study, please do this in consultation
           with the clinician that prescribed your sleep medication. Please note that
           discontinuation of your current sleep medication will make it necessary to extend the
           baseline component of our study by at least two weeks. Should the sleep diaries indicate
           that your insomnia is not of the type, severity, or frequency required for the study,
           you will not be able to continue in the study but will be provided with a referral. This
           referral will be for the Penn Sleep Disorder Center. If you or study personnel deem your
           two weeks to be unusual, you may be offered the chance to repeat the baseline period.

      Phase-3: Sleep Lab Study (polysomnography) or Home Sleep Apnea Test (HSAT). You will undergo
      a polysomnography study or an HSAT to determine if you are eligible to continue in the study.
      During the pandemic all sleep tests will be administered at home. After the pandemic, the
      study investigators will decide which type of study you will receive. Both sleep assessments
      will last for 1 night.

      The HSAT equipment will be shipped to your house. A member of the study team will contact you
      to go over proper use instructions. On the night of the test, you can go to bed at your
      regular bedtime. Prior to bedtime, you will attach the sensor(s) as instructed and start the
      test. Upon waking up, you will stop the test and remove the sensor(s). On the day immediately
      following the sleep test, you will ship the device back in the prepaid shipping envelope
      Procedures for the polysomnography study are: you will be asked to arrive at the sleep lab
      located at the Hospital of the University of Pennsylvania (HUP) at the cross streets of 34th
      and Spruce by 7 P.M. for a polysomnographic study (PSG). Upon arrival, to ensure for accurate
      laboratory measurements, urine toxicology screens may be performed to rule out illegal
      substance use. These data are acquired to explain abnormal findings on the PSG. Following the
      sleep study, it will be determined whether a repeat study is necessary based on the findings
      both from the clinical chemistries and the polysomnography. If a repeat study is necessary,
      one of the project investigators will discuss the issue of substance use with you to: (1)
      determine if the clinical chemistries' finding was an error (for example poppy seeds led to a
      positive screen) or (2) gain your willingness to refrain from substance use for the second
      PSG and for the remainder of the study. If you screen positive a second time, your
      participation will be discontinued.

      The specific procedure for a PSG requires that you have a set of sensors placed on your face,
      scalp, and body by a technician. All the sensors are attached with surgical tape, paste and
      glue. The sensors on your face are attached on your left and right temple, cheek bone and
      under your nose. The sensors on the temple and cheek bone measure eye movements associated
      with falling asleep and dreaming. The sensors under your nose measure airflow through your
      mouth and nose. The sensors on your scalp measure brain waves during sleep. The sensors on
      the body are placed above the collar bones and over the calf muscles. The sensors over the
      collar bones measure heart muscle activity. The sensors over the calf muscles measure muscle
      activity from the legs. In addition, a strap will be placed around your chest and abdomen to
      measure respiration.

      After you have been connected to the equipment, you are expected to stay in bed until final
      wake time the next morning, except for bathroom breaks. You will be visually monitored by the
      lab technicians by remote video. In the morning, you will be awakened by the technician (if
      needed), be unhooked from the equipment, and then allowed to shower, dress, and eat before
      leaving. You will be free to go about your normal schedule for the rest of the day.

      If the in-lab PSG sleep or HSAT study finds evidence of a sleep disorder other than insomnia,
      such as sleep apnea, you will not be able to continue in the study but will be provided with
      a referral.

      Phase-4: Standard Treatment. All participating subjects will receive one month of standard
      nightly treatment. If you have a positive treatment response you will remain in the study and
      be randomized to one of the following treatment conditions: nightly dosing, intermittent
      dosing (1-3 pills week, full dose), or one of two variable dose conditions (nightly pill use
      where any given pill is a variable dose). The assignment of condition will be accomplished by
      a process that is the same as the flip of a coin and neither you nor the study personnel will
      know which condition you have been assigned to (this is referred to as a "double blind"
      study). You will have an equal chance of being randomized to each of the 4 study arms. In the
      case of an emergency, the blind will be broken and the study doctor and clinicians associated
      with your care will be informed of which dosing condition you were assigned to.

      Standard treatment will last for 4 weeks. The experimental phase will extend over two
      periods. The first period will last for 12 weeks. The second period will last for 36 weeks.

      Both periods include:

        -  Taking a pill 30 minutes prior to bedtime. In one case, this will involve taking 1-3
           pills per week. In the remaining conditions, pills will be taken on each and every
           night. Depending on the specific group you are assigned to, you will either receive 10mg
           or 5mg of zolpidem (variable by age and sex) or a variable dose of zolpidem on a nightly
           basis (range from 0 mg to 10 mg per night). Please note that the effect of zolpidem may
           be slowed if taken with or immediately after a meal.

        -  Completing a sleep diary each day;

        -  Completing 6 to 7 questionnaires each week;

        -  A monthly visit to Penn to return your medication foil packs and to receive a new foil
           pack with the next month of medication.

      If you do not experience a treatment response or (following a treatment response) you
      experience a relapse of insomnia, you will not be able to continue in the study but will be
      given the opportunity to be treated with Cognitive Behavioral Therapy for Insomnia (CBT-I) at
      no cost. Assessments of your clinical status (how your insomnia is responding to treatment)
      will be based on your daily sleep diaries and weekly questionnaires.

      During Phase-4, you will be asked to undergo quarter annual physicals so that we can
      optimally track your health and wellbeing. The physicals will involve standard vital measures
      (e.g., temperature, blood pressure, height and weight, etc.) and, based on the judgement of
      the research clinician, may involve an EKG and/or blood and urine chemistries.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double Blinded
measure: Insomnia Relapse
time frame: 1 year
description: Tracking Relapse via assessing daily sleep diary responses.
measure: Sleep Continuity
time frame: 1 year
description: Assess sleep continuity by assessing daily sleep diary responses.
arm group label: Continuous
arm group type: Experimental
description: Nightly active dose (QHS). The intervention is zolpidem tartrate 5 mg or 10 mg.
arm group label: Partial Reinforcement 1
arm group type: Experimental
description: 1 active dose per week with 6 placebos interspersed between the active dose. The intervention is zolpidem tartrate 5 mg or 10 mg.
arm group label: Partial Reinforcement 3
arm group type: Experimental
description: 3 active doses per week with 4 placebos interspersed between the active doses. The intervention is zolpidem tartrate 5 mg or 10 mg.
arm group label: Low Frequency Intermittent Dosing
arm group type: Experimental
description: 1 to 3 active doses per week PRN. The intervention is zolpidem tartrate 5 mg or 10 mg.
intervention type: Drug
intervention name: Zolpidem tartrate
description: Zolpidem Tartrate, 5mg for men older than 60 and women of all ages. 10 mg for men younger than 60.
arm group label: Continuous
arm group label: Low Frequency Intermittent Dosing
arm group label: Partial Reinforcement 1
arm group label: Partial Reinforcement 3
other name: zolpidem
other name: ambien
criteria: 
gender: All
minimum age: 40 Years
maximum age: 85 Years
healthy volunteers: No
last name: Michael L Perlis, PhD
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
url: http://www.sleeplessinphilly.com
description: Click here to learn about our available studies
url: http://www.med.upenn.edu/bsm/
description: Click here to learn more about our sleep research laboratory
responsible party type: Sponsor
mesh term: Sleep Initiation and Maintenance Disorders
mesh term: Zolpidem
sharing ipd: No
provided document: 
provided document: 