<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/NCT03772314</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00108167</org_study_id>
    <nct_id>NCT03772314</nct_id>
  </id_info>
  <brief_title>Modafinil Versus Amphetamines for the Treatment of Narcolepsy Type 2 and Idiopathic Hypersomnia</brief_title>
  <official_title>Informing Treatment Decisions in the Central Disorders of Hypersomnolence: A Pragmatic Clinical Trial of Modafinil Versus Amphetamines</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>American Academy of Sleep Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      For diseases that cause excessive daytime sleepiness (such as narcolepsy and idiopathic&#xD;
      hypersomnia), there are several medications that can be used to treat sleepiness. However, it&#xD;
      can be difficult to decide which medication to use for a particular individual for several&#xD;
      reasons: 1) there are very few studies that directly compare two medications to see which&#xD;
      works best; 2) there are very few studies that include people with a disorder of sleepiness&#xD;
      called idiopathic hypersomnia.&#xD;
&#xD;
      To address this gap in knowledge, the researchers propose a randomized clinical trial&#xD;
      comparing modafinil and amphetamine salts in patients with narcolepsy type 2 or idiopathic&#xD;
      hypersomnia. All participants will either receive modafinil or amphetamine salts -- no&#xD;
      participant will receive placebo.&#xD;
&#xD;
      This study will evaluate which medication works better to improve sleepiness. The researchers&#xD;
      will also see which medication is better for other symptoms including difficulty waking up&#xD;
      and difficulty thinking, as well as seeing which medication causes fewer side. Finally, this&#xD;
      study will see if any information about patients (such as age or sleep study features)&#xD;
      predicts responding better to one medication or the other.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Currently, there are insufficient data to guide clinical practice regarding the use of&#xD;
      amphetamines for the treatment of narcolepsy. This may be particularly important in the case&#xD;
      of narcolepsy type 2, for which randomized, controlled trial data show that other treatments&#xD;
      are less beneficial than they are for participants with narcolepsy type 1. For the closely&#xD;
      related disorder of idiopathic hypersomnia, clinical trial data to guide treatment&#xD;
      decision-making are even more limited, with only three published controlled trials ever&#xD;
      performed.&#xD;
&#xD;
      To address these evidence gaps, the researchers propose a randomized, active-treatment&#xD;
      controlled trial comparing modafinil and amphetamine salts for the treatment of narcolepsy&#xD;
      type 2 and idiopathic hypersomnia. The primary outcome will be reduction in excessive daytime&#xD;
      sleepiness, as measured by change in Epworth Sleepiness Scale scores from baseline to week 12&#xD;
      on treatment. Other important patient-reported outcomes will be considered as secondary&#xD;
      outcomes, including Patient Global Impression of Change for overall severity, sleep inertia,&#xD;
      cognitive dysfunction, and sleepiness, as well as other symptom questionnaires.&#xD;
&#xD;
      In addition to directly comparing the efficacy of these two medications for hypersomnolent&#xD;
      patients, this study will also evaluate for relatively safety in this population. Further,&#xD;
      this study will assess clinical predictors of treatment response. All three of these aims&#xD;
      will be complementary in informing shared decision-making about whether to treat with&#xD;
      modafinil or amphetamine salts.&#xD;
&#xD;
      Forty-four adult patients seeking evaluation at the Emory Sleep Center for narcolepsy type 2&#xD;
      or idiopathic hypersomnia will be invited to participate and will be randomized to one of the&#xD;
      treatment arms upon consent. Participants will receive study treatment for 12 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 15, 2019</start_date>
  <completion_date type="Actual">April 3, 2023</completion_date>
  <primary_completion_date type="Actual">April 3, 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Epworth Sleepiness Scale (ESS) Score</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The Epworth Sleepiness Scale (ESS) asks respondents to indicate how likely they are to doze off or fall asleep during daytime situations such as reading or talking to someone. There are 8 items which are answered on a scale of 0 to 4 where 0 = would never doze and 4 = high chance of dozing. Total score can range from 0 to 24, with higher scores indicating more sleepiness. A score of 0 to 5 can be interpreted as &quot;lower normal daytime sleepiness&quot;, a score of 6 to 10 is &quot;higher normal daytime sleepiness&quot;, score between 11 to 12 are &quot;mild excessive daytime sleepiness, scores of 13 to 15 are &quot;moderate excessive daytime sleepiness&quot; and scores of 16 to 24 indicate &quot;severe excessive daytime sleepiness&quot;.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Patient Global Impression of Change (PGIc) for Sleepiness Score</measure>
    <time_frame>Weeks 4, 8, 12</time_frame>
    <description>The PGIc for Sleepiness asks respondents to rate their sleepiness compared to baseline. Responses are indicated on a scale of 1 to 7 where 1 = very much improved and 7 = very much worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Patient Global Impression of Change (PGIc) for Sleep Inertia Score</measure>
    <time_frame>Weeks 4, 8, 12</time_frame>
    <description>The PGIc for Sleep Inertia asks respondents to rate their sleep interia compared to baseline. Sleep inertia is defined for participants as &quot;difficulty waking up and getting out of bed in the morning because of sleepiness&quot;. Responses are indicated on a scale of 1 to 7 where 1 = very much improved and 7 = very much worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Patient Global Impression of Change (PGIc) for Cognitive Dysfunction Score</measure>
    <time_frame>Weeks 4, 8, 12</time_frame>
    <description>The PGIc for Cognitive Dysfunction asks respondents to rate their cognitive dysfunction compared to baseline. Cognitive dysfunction is defined for participants as &quot;difficulty with thinking, problems with attention or concentration, and/or brain fog&quot;. Responses are indicated on a scale of 1 to 7 where 1 = very much improved and 7 = very much worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Patient Global Impression of Change (PGIc) for Overall Disease Severity Score</measure>
    <time_frame>Weeks 4, 8, 12</time_frame>
    <description>The PGIc for Overall Severity asks respondents to rate their overall disease compared to baseline. Responses are indicated on a scale of 1 to 7 where 1 = very much improved and 7 = very much worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Hypersomnia Severity Index (HSI) from Baseline</measure>
    <time_frame>Baseline, Weeks 4, 8, 12</time_frame>
    <description>The HSI is a 9-item instrument assessing the severity of excessive sleepiness (hypersomnolence). Items are scored on a Likert scale where 0 = not at all and 4 = very much. Total scores range from 0 to 36 and higher scores indicate greater severity of symptoms of hypersomnia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Sleep Inertia Questionnaire (SIQ) from Baseline</measure>
    <time_frame>Baseline, Weeks 4, 8, 12</time_frame>
    <description>The SIQ is an instrument with 21 items with responses on a 5-point scale where 1 = &quot;not at all&quot; and 5 = &quot;all the time&quot;. Two additional questions relate to how much time it takes for the respondent to wake up in the morning. Total scores range from 21 to 105 and higher scores indicate increased difficulty from tiredness.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Idiopathic Hypersomnia</condition>
  <condition>Narcolepsy Without Cataplexy</condition>
  <arm_group>
    <arm_group_label>Modafinil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in this study arm will take modafinil.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Amphetamine-dextroamphetamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this study arm will take amphetamine-dextroamphetamine (amphetamine salts).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Modafinil</intervention_name>
    <description>Participants will received 100-400 milligrams (mg) per day of modafinil for 12 weeks.</description>
    <arm_group_label>Modafinil</arm_group_label>
    <other_name>Provigil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amphetamine-Dextroamphetamine</intervention_name>
    <description>Participants will receive 10-40 mg/day of oral amphetamine salts for 12 weeks.</description>
    <arm_group_label>Amphetamine-dextroamphetamine</arm_group_label>
    <other_name>Adderall</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  narcolepsy type 2 or idiopathic hypersomnia&#xD;
&#xD;
          -  ability to give informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  contraindication to modafinil or amphetamine salts (history of left ventricular&#xD;
             hypertrophy, mitral valve prolapse, other cardiac structural abnormalities, severe&#xD;
             cardiovascular disease, unstable angina, myocardial infarction, cardiomyopathy, severe&#xD;
             arrhythmias, uncontrolled hypertension, severe hepatic impairment, substance abuse&#xD;
             history, psychosis, glaucoma, Tourette's syndrome, and epilepsy)&#xD;
&#xD;
          -  obstructive sleep apnea (Apnea-Hypopnea Index (AHI) &gt; 15)&#xD;
&#xD;
          -  severe periodic limb movements of sleep with arousals (periodic limb movements (PLM)&#xD;
             arousal index &gt; 30)&#xD;
&#xD;
          -  allergy to either of the study drugs&#xD;
&#xD;
          -  pregnancy or breastfeeding&#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>Lynn Marie Trotti, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory Sleep Center</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30329</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>April 13, 2023</last_update_submitted>
  <last_update_submitted_qc>April 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Lynn Marie Trotti</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Narcolepsy</mesh_term>
    <mesh_term>Disorders of Excessive Somnolence</mesh_term>
    <mesh_term>Cataplexy</mesh_term>
    <mesh_term>Idiopathic Hypersomnia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Modafinil</mesh_term>
    <mesh_term>Amphetamine</mesh_term>
    <mesh_term>Adderall</mesh_term>
    <mesh_term>Dextroamphetamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03772314
org study id: IRB00108167
nct id: NCT03772314
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
For diseases that cause excessive daytime sleepiness (such as narcolepsy and idiopathic
      hypersomnia), there are several medications that can be used to treat sleepiness. However, it
      can be difficult to decide which medication to use for a particular individual for several
      reasons: 1) there are very few studies that directly compare two medications to see which
      works best; 2) there are very few studies that include people with a disorder of sleepiness
      called idiopathic hypersomnia.

      To address this gap in knowledge, the researchers propose a randomized clinical trial
      comparing modafinil and amphetamine salts in patients with narcolepsy type 2 or idiopathic
      hypersomnia. All participants will either receive modafinil or amphetamine salts -- no
      participant will receive placebo.

      This study will evaluate which medication works better to improve sleepiness. The researchers
      will also see which medication is better for other symptoms including difficulty waking up
      and difficulty thinking, as well as seeing which medication causes fewer side. Finally, this
      study will see if any information about patients (such as age or sleep study features)
      predicts responding better to one medication or the other.
Currently, there are insufficient data to guide clinical practice regarding the use of
      amphetamines for the treatment of narcolepsy. This may be particularly important in the case
      of narcolepsy type 2, for which randomized, controlled trial data show that other treatments
      are less beneficial than they are for participants with narcolepsy type 1. For the closely
      related disorder of idiopathic hypersomnia, clinical trial data to guide treatment
      decision-making are even more limited, with only three published controlled trials ever
      performed.

      To address these evidence gaps, the researchers propose a randomized, active-treatment
      controlled trial comparing modafinil and amphetamine salts for the treatment of narcolepsy
      type 2 and idiopathic hypersomnia. The primary outcome will be reduction in excessive daytime
      sleepiness, as measured by change in Epworth Sleepiness Scale scores from baseline to week 12
      on treatment. Other important patient-reported outcomes will be considered as secondary
      outcomes, including Patient Global Impression of Change for overall severity, sleep inertia,
      cognitive dysfunction, and sleepiness, as well as other symptom questionnaires.

      In addition to directly comparing the efficacy of these two medications for hypersomnolent
      patients, this study will also evaluate for relatively safety in this population. Further,
      this study will assess clinical predictors of treatment response. All three of these aims
      will be complementary in informing shared decision-making about whether to treat with
      modafinil or amphetamine salts.

      Forty-four adult patients seeking evaluation at the Emory Sleep Center for narcolepsy type 2
      or idiopathic hypersomnia will be invited to participate and will be randomized to one of the
      treatment arms upon consent. Participants will receive study treatment for 12 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Epworth Sleepiness Scale (ESS) Score
time frame: Baseline, Week 12
description: The Epworth Sleepiness Scale (ESS) asks respondents to indicate how likely they are to doze off or fall asleep during daytime situations such as reading or talking to someone. There are 8 items which are answered on a scale of 0 to 4 where 0 = would never doze and 4 = high chance of dozing. Total score can range from 0 to 24, with higher scores indicating more sleepiness. A score of 0 to 5 can be interpreted as "lower normal daytime sleepiness", a score of 6 to 10 is "higher normal daytime sleepiness", score between 11 to 12 are "mild excessive daytime sleepiness, scores of 13 to 15 are "moderate excessive daytime sleepiness" and scores of 16 to 24 indicate "severe excessive daytime sleepiness".
measure: Change in Patient Global Impression of Change (PGIc) for Sleepiness Score
time frame: Weeks 4, 8, 12
description: The PGIc for Sleepiness asks respondents to rate their sleepiness compared to baseline. Responses are indicated on a scale of 1 to 7 where 1 = very much improved and 7 = very much worse.
measure: Change in Patient Global Impression of Change (PGIc) for Sleep Inertia Score
time frame: Weeks 4, 8, 12
description: The PGIc for Sleep Inertia asks respondents to rate their sleep interia compared to baseline. Sleep inertia is defined for participants as "difficulty waking up and getting out of bed in the morning because of sleepiness". Responses are indicated on a scale of 1 to 7 where 1 = very much improved and 7 = very much worse.
measure: Change in Patient Global Impression of Change (PGIc) for Cognitive Dysfunction Score
time frame: Weeks 4, 8, 12
description: The PGIc for Cognitive Dysfunction asks respondents to rate their cognitive dysfunction compared to baseline. Cognitive dysfunction is defined for participants as "difficulty with thinking, problems with attention or concentration, and/or brain fog". Responses are indicated on a scale of 1 to 7 where 1 = very much improved and 7 = very much worse.
measure: Change in Patient Global Impression of Change (PGIc) for Overall Disease Severity Score
time frame: Weeks 4, 8, 12
description: The PGIc for Overall Severity asks respondents to rate their overall disease compared to baseline. Responses are indicated on a scale of 1 to 7 where 1 = very much improved and 7 = very much worse.
measure: Change in Hypersomnia Severity Index (HSI) from Baseline
time frame: Baseline, Weeks 4, 8, 12
description: The HSI is a 9-item instrument assessing the severity of excessive sleepiness (hypersomnolence). Items are scored on a Likert scale where 0 = not at all and 4 = very much. Total scores range from 0 to 36 and higher scores indicate greater severity of symptoms of hypersomnia.
measure: Change in Sleep Inertia Questionnaire (SIQ) from Baseline
time frame: Baseline, Weeks 4, 8, 12
description: The SIQ is an instrument with 21 items with responses on a 5-point scale where 1 = "not at all" and 5 = "all the time". Two additional questions relate to how much time it takes for the respondent to wake up in the morning. Total scores range from 21 to 105 and higher scores indicate increased difficulty from tiredness.
arm group label: Modafinil
arm group type: Active Comparator
description: Participants in this study arm will take modafinil.
arm group label: Amphetamine-dextroamphetamine
arm group type: Experimental
description: Participants in this study arm will take amphetamine-dextroamphetamine (amphetamine salts).
intervention type: Drug
intervention name: Modafinil
description: Participants will received 100-400 milligrams (mg) per day of modafinil for 12 weeks.
arm group label: Modafinil
other name: Provigil
intervention type: Drug
intervention name: Amphetamine-Dextroamphetamine
description: Participants will receive 10-40 mg/day of oral amphetamine salts for 12 weeks.
arm group label: Amphetamine-dextroamphetamine
other name: Adderall
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Lynn Marie Trotti, MD, MSc
role: Principal Investigator
affiliation: Emory University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Lynn Marie Trotti
investigator title: Associate Professor
mesh term: Narcolepsy
mesh term: Disorders of Excessive Somnolence
mesh term: Cataplexy
mesh term: Idiopathic Hypersomnia
mesh term: Modafinil
mesh term: Amphetamine
mesh term: Adderall
mesh term: Dextroamphetamine
sharing ipd: No