<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/NCT04429347</url>
  </required_header>
  <id_info>
    <org_study_id>191167</org_study_id>
    <secondary_id>UL1TR000100</secondary_id>
    <nct_id>NCT04429347</nct_id>
  </id_info>
  <brief_title>Gabapentin and Tizanidine for Insomnia in Chronic Pain</brief_title>
  <official_title>Effect of Gabapentin and Tizanidine on Insomnia in Chronic Pain Patients: A Randomized, Double-blind, Placebo-controlled Crossover Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Center for Advancing Translational Sciences (NCATS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Diego</source>
  <oversight_info>
    <has_dmc>No</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>
      This is a double-blind, placebo-controlled, randomized, crossover trial aimed at assessing&#xD;
      the effect of gabapentin and tizanidine, two pain medications, on insomnia in chronic pain&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic pain and insomnia are highly prevalent conditions affecting 10-25% and 6-10% of the&#xD;
      general population, respectively. Importantly, these two conditions frequently co-occur, with&#xD;
      50-80% of chronic pain patients reporting sleep disturbances. Identifying medication that&#xD;
      alleviates pain and insomnia simultaneously may help reduce risks associated with&#xD;
      polypharmacy, including drug-drug interactions.&#xD;
&#xD;
      In this double-blind, placebo-controlled, randomized, crossover trial, gabapentin and&#xD;
      tizanidine, two drugs which are respectively commonly used to treat neuropathic and&#xD;
      musculoskeletal pain, will be compared to each other and to placebo in their ability to&#xD;
      alleviate insomnia in chronic pain patients.&#xD;
&#xD;
      In each week, patients will receive 3-night (Friday-Sunday) trials each of placebo,&#xD;
      gabapentin or tizanidine in a randomized, double-blind order and will monitor their insomnia&#xD;
      using the Athens Insomnia Scale (AIS) questionnaire (adapted to fit the time frame of this&#xD;
      trial). The primary outcome consists of the difference in mean AIS scores between the 3&#xD;
      treatments at the primary time point, which is Monday of each week (after 3 nights of drug&#xD;
      intake).&#xD;
&#xD;
      Patients will also monitor their sleepiness, pain relief and overall improvement as secondary&#xD;
      variants using the Stanford Sleepiness Scale (SSS), Visual Analog Scale (VAS), and Patient's&#xD;
      Global Impression of Change (PGIC) questionnaires respectively.&#xD;
&#xD;
      Scores on the Monday preceding the first treatment will serve as baseline and the period&#xD;
      between treatments (i.e. Monday-Thursday nights) will serve as a 4-day washout period between&#xD;
      treatments.&#xD;
&#xD;
      Our hypothesis is that gabapentin and tizanidine will both be more effective than placebo in&#xD;
      alleviating insomnia in chronic pain patients but will not be different from one another.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">July 29, 2020</start_date>
  <completion_date type="Anticipated">July 29, 2024</completion_date>
  <primary_completion_date type="Anticipated">July 29, 2023</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>Crossover Assignment</intervention_model>
    <intervention_model_description>Randomized, Double-bind, Placebo-controlled, Crossover Trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Each participant will have an identification number and randomization of drug sequence allocation will be performed a priori using a random number generator by the study pharmacist. The 3 treatments will be identically encapsulated by the study pharmacist. The study pharmacist will place the drug capsules in identical sealed plastic bags labeled &quot;Treatment 1&quot; through &quot;Treatment 3&quot;.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Sleep quality</measure>
    <time_frame>Monday after 3 nights of drug intake</time_frame>
    <description>Comparison of group means for Athens Insomnia Scale scores between the 3 treatment groups placebo, gabapentin and tizanidine.&#xD;
Total Athens Insomnia Scale score ranges from 0 to 24. The higher the score, the more severe the insomnia symptoms experienced by the patient.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain Intensity</measure>
    <time_frame>Monday after 3 nights of drug intake</time_frame>
    <description>Comparison of group means for Visual Analog Scale scores between the 3 treatment groups placebo, gabapentin and tizanidine.&#xD;
Visual Analog Scale score ranges from 0 to 10. The higher the score, the worse the pain experienced by the patient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alertness</measure>
    <time_frame>Monday after 3 nights of drug intake</time_frame>
    <description>Comparison of group means for Stanford Sleepiness Scale scores between the 3 treatment groups placebo, gabapentin and tizanidine.&#xD;
Stanford Sleepiness Scale score ranges from 1 to 7. The higher the score, the more sleepy and less alert the patient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall improvement</measure>
    <time_frame>Monday after 3 nights of drug intake</time_frame>
    <description>Comparison of group means for Patient Global Impression of Change scores between the 3 treatment groups placebo, gabapentin and tizanidine.&#xD;
Patient Global Impression of Change score ranges from 1 to 7. The higher the score, the more improvement reported by the patient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Categorical assessment of insomnia improvement</measure>
    <time_frame>Monday after 3 nights of drug intake</time_frame>
    <description>Percentage of patients with a 30% improvement from baseline in individual Athens Insomnia Scale scores for each of the 3 treatments placebo, gabapentin and tizanidine.&#xD;
Total Athens Insomnia Scale score ranges from 0 to 24. The higher the scores, the more severe the insomnia symptoms experienced by the patient.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Insomnia Due to Medical Condition</condition>
  <condition>Chronic Pain</condition>
  <arm_group>
    <arm_group_label>Tizanidine 2mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Friday night: 1 capsule Saturday night: 2 capsules Sunday night: Subject chooses 1-2 capsules</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gabapentin 300mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Friday night: 1 capsule Saturday night: 2 capsules Sunday night: Subject chooses 1-2 capsules</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Friday night: 1 capsule Saturday night: 2 capsules Sunday night: Subject chooses 1-2 capsules</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gabapentin</intervention_name>
    <description>Friday night: 1 capsule of 300 mg, Saturday night: 2 capsule of 300 mg (total 600 mg), Sunday night: choice of 1 or 2 capsule of 300 mg (total of 300 or 600 mg)</description>
    <arm_group_label>Gabapentin 300mg</arm_group_label>
    <other_name>Neurontin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Friday night: 1 capsule, Saturday night: 2 capsule, Sunday night: choice of 1 or 2 capsules</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Sham</other_name>
    <other_name>Sugar Pill</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tizanidine</intervention_name>
    <description>Friday night: 1 capsule of 2 mg, Saturday night: 2 capsule of 2 mg (total 4 mg), Sunday night: choice of 1 or 2 capsules of 2 mg (total of 2 or 4 mg)</description>
    <arm_group_label>Tizanidine 2mg</arm_group_label>
    <other_name>Zanaflex</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  BMI ≤ 35&#xD;
&#xD;
          -  Any ethnicity&#xD;
&#xD;
          -  Must be able to communicate in English&#xD;
&#xD;
          -  Must have access to email and be able to respond to REDCap questionnaires in English&#xD;
&#xD;
          -  Has a chronic pain condition (≥ 3 months of pain)&#xD;
&#xD;
          -  Reports sleep disturbance and scores ≥ 6 on AIS questionnaire&#xD;
&#xD;
          -  Ability to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Breastfeeding&#xD;
&#xD;
          -  Has diagnosis of chronic kidney disease&#xD;
&#xD;
          -  Has known QT prolongation &gt;500 msec on prior EKG&#xD;
&#xD;
          -  Inability to complete daily questionnaires&#xD;
&#xD;
          -  Allergy to, or intolerance of, any of tizanidine or gabapentin&#xD;
&#xD;
          -  Shift workers&#xD;
&#xD;
          -  Anticipated travel across multiple time zones (jetlag) during the duration of the&#xD;
             trial&#xD;
&#xD;
          -  Circadian misalignment&#xD;
&#xD;
          -  Prior syncope experience and/or fear of blood/needles (if a blood draw is required)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nathaniel Schuster, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UC San Diego</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Pain Medicine, UC San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>September 8, 2022</last_update_submitted>
  <last_update_submitted_qc>September 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Diego</investigator_affiliation>
    <investigator_full_name>Nathaniel Schuster</investigator_full_name>
    <investigator_title>Assistant Profesor</investigator_title>
  </responsible_party>
  <keyword>Insomnia</keyword>
  <keyword>Chronic Pain</keyword>
  <keyword>Gabapentin</keyword>
  <keyword>Tizanidine</keyword>
  <keyword>Placebo</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Initiation and Maintenance Disorders</mesh_term>
    <mesh_term>Chronic Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gabapentin</mesh_term>
    <mesh_term>Tizanidine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Deidentified data will be shared in a manner TBD based on funding availability and journal requirements.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Beginning 12 months and ending 3 years following article publication.</ipd_time_frame>
    <ipd_access_criteria>Researchers who provide a methodologically sound proposal. Proposals should be sent to nmschuster@health.ucsd.edu.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04429347
org study id: 191167
secondary id: UL1TR000100
nct id: NCT04429347
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a double-blind, placebo-controlled, randomized, crossover trial aimed at assessing
      the effect of gabapentin and tizanidine, two pain medications, on insomnia in chronic pain
      patients.
Chronic pain and insomnia are highly prevalent conditions affecting 10-25% and 6-10% of the
      general population, respectively. Importantly, these two conditions frequently co-occur, with
      50-80% of chronic pain patients reporting sleep disturbances. Identifying medication that
      alleviates pain and insomnia simultaneously may help reduce risks associated with
      polypharmacy, including drug-drug interactions.

      In this double-blind, placebo-controlled, randomized, crossover trial, gabapentin and
      tizanidine, two drugs which are respectively commonly used to treat neuropathic and
      musculoskeletal pain, will be compared to each other and to placebo in their ability to
      alleviate insomnia in chronic pain patients.

      In each week, patients will receive 3-night (Friday-Sunday) trials each of placebo,
      gabapentin or tizanidine in a randomized, double-blind order and will monitor their insomnia
      using the Athens Insomnia Scale (AIS) questionnaire (adapted to fit the time frame of this
      trial). The primary outcome consists of the difference in mean AIS scores between the 3
      treatments at the primary time point, which is Monday of each week (after 3 nights of drug
      intake).

      Patients will also monitor their sleepiness, pain relief and overall improvement as secondary
      variants using the Stanford Sleepiness Scale (SSS), Visual Analog Scale (VAS), and Patient's
      Global Impression of Change (PGIC) questionnaires respectively.

      Scores on the Monday preceding the first treatment will serve as baseline and the period
      between treatments (i.e. Monday-Thursday nights) will serve as a 4-day washout period between
      treatments.

      Our hypothesis is that gabapentin and tizanidine will both be more effective than placebo in
      alleviating insomnia in chronic pain patients but will not be different from one another.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Randomized, Double-bind, Placebo-controlled, Crossover Trial
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Each participant will have an identification number and randomization of drug sequence allocation will be performed a priori using a random number generator by the study pharmacist. The 3 treatments will be identically encapsulated by the study pharmacist. The study pharmacist will place the drug capsules in identical sealed plastic bags labeled "Treatment 1" through "Treatment 3".
measure: Sleep quality
time frame: Monday after 3 nights of drug intake
description: Comparison of group means for Athens Insomnia Scale scores between the 3 treatment groups placebo, gabapentin and tizanidine.
Total Athens Insomnia Scale score ranges from 0 to 24. The higher the score, the more severe the insomnia symptoms experienced by the patient.
measure: Pain Intensity
time frame: Monday after 3 nights of drug intake
description: Comparison of group means for Visual Analog Scale scores between the 3 treatment groups placebo, gabapentin and tizanidine.
Visual Analog Scale score ranges from 0 to 10. The higher the score, the worse the pain experienced by the patient.
measure: Alertness
time frame: Monday after 3 nights of drug intake
description: Comparison of group means for Stanford Sleepiness Scale scores between the 3 treatment groups placebo, gabapentin and tizanidine.
Stanford Sleepiness Scale score ranges from 1 to 7. The higher the score, the more sleepy and less alert the patient.
measure: Overall improvement
time frame: Monday after 3 nights of drug intake
description: Comparison of group means for Patient Global Impression of Change scores between the 3 treatment groups placebo, gabapentin and tizanidine.
Patient Global Impression of Change score ranges from 1 to 7. The higher the score, the more improvement reported by the patient.
measure: Categorical assessment of insomnia improvement
time frame: Monday after 3 nights of drug intake
description: Percentage of patients with a 30% improvement from baseline in individual Athens Insomnia Scale scores for each of the 3 treatments placebo, gabapentin and tizanidine.
Total Athens Insomnia Scale score ranges from 0 to 24. The higher the scores, the more severe the insomnia symptoms experienced by the patient.
arm group label: Tizanidine 2mg
arm group type: Experimental
description: Friday night: 1 capsule Saturday night: 2 capsules Sunday night: Subject chooses 1-2 capsules
arm group label: Gabapentin 300mg
arm group type: Experimental
description: Friday night: 1 capsule Saturday night: 2 capsules Sunday night: Subject chooses 1-2 capsules
arm group label: Placebo
arm group type: Placebo Comparator
description: Friday night: 1 capsule Saturday night: 2 capsules Sunday night: Subject chooses 1-2 capsules
intervention type: Drug
intervention name: Gabapentin
description: Friday night: 1 capsule of 300 mg, Saturday night: 2 capsule of 300 mg (total 600 mg), Sunday night: choice of 1 or 2 capsule of 300 mg (total of 300 or 600 mg)
arm group label: Gabapentin 300mg
other name: Neurontin
intervention type: Drug
intervention name: Placebo
description: Friday night: 1 capsule, Saturday night: 2 capsule, Sunday night: choice of 1 or 2 capsules
arm group label: Placebo
other name: Sham
other name: Sugar Pill
intervention type: Drug
intervention name: Tizanidine
description: Friday night: 1 capsule of 2 mg, Saturday night: 2 capsule of 2 mg (total 4 mg), Sunday night: choice of 1 or 2 capsules of 2 mg (total of 2 or 4 mg)
arm group label: Tizanidine 2mg
other name: Zanaflex
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Nathaniel Schuster, MD
role: Principal Investigator
affiliation: UC San Diego
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, San Diego
investigator full name: Nathaniel Schuster
investigator title: Assistant Profesor
mesh term: Sleep Initiation and Maintenance Disorders
mesh term: Chronic Pain
mesh term: Gabapentin
mesh term: Tizanidine
sharing ipd: Yes
ipd description: Deidentified data will be shared in a manner TBD based on funding availability and journal requirements.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Beginning 12 months and ending 3 years following article publication.
ipd access criteria: Researchers who provide a methodologically sound proposal. Proposals should be sent to nmschuster@health.ucsd.edu.