<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/NCT02256865</url>
  </required_header>
  <id_info>
    <org_study_id>30068-01</org_study_id>
    <nct_id>NCT02256865</nct_id>
  </id_info>
  <brief_title>Hormonal Mechanisms of Sleep Restriction</brief_title>
  <official_title>Hormonal Mechanisms of Sleep Restriction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to study the effects of sleep restriction on the production of&#xD;
      two hormones, cortisol and testosterone. The investigators aim to show that changing these&#xD;
      hormones leads to insulin resistance, which is an important cause of type 2 diabetes&#xD;
      mellitus. The investigators may also study the effect of sleep restriction on your food&#xD;
      intake and cravings, mood, inflammation, metabolism (including bone), and other hormones.&#xD;
      Inflammation is your body's response to stress and injury. Bone metabolism is a process of&#xD;
      how your body regenerates (renews) new bone cells and removes old bone cells. Hormones are&#xD;
      natural substances (materials) that are produced in the body and that influences (effects)&#xD;
      the way the body grows or develops.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Screening Visits&#xD;
&#xD;
        -  To see if you are able to take part in this study, you will first have an outpatient&#xD;
           visit at the CTRC (Clinical and Translational Research Center). This visit will take&#xD;
           about 90 minutes.&#xD;
&#xD;
        -  The following tests/procedures will be done at this visit:&#xD;
&#xD;
             -  We will ask you about your medical history and past health&#xD;
&#xD;
             -  We will give you a physical examination (including digital rectal examination of&#xD;
                the prostate gland if you are over the age of 40)&#xD;
&#xD;
             -  We will ask you to answer sleep, mood and general health screening questionnaires.&#xD;
&#xD;
             -  We will ask you to complete a questionnaire to help us understand how testosterone&#xD;
                and other hormones control sexual function and drive.&#xD;
&#xD;
             -  We will draw about 1 tablespoon of blood from a needle placed in a vein in your arm&#xD;
                for routine safety tests and to check to see if you have any hormonal problems.&#xD;
&#xD;
             -  We will give you an ECG (recording of heartbeat). For this test we will attach&#xD;
                12-lead sensors to your chest.&#xD;
&#xD;
             -  We will collect urine sample from you for a drug screening test.&#xD;
&#xD;
             -  A dietitian will review meal plans for the inpatient stay (Study Visit 1 and 3&#xD;
                only).&#xD;
&#xD;
      If the first screening visit shows that you are able to continue to take part in this study,&#xD;
      you will continue the screening part of the study at home. The following will be done at&#xD;
      home: We will ask you to undergo an at-home actigraphy and keep a daily sleep diary for two&#xD;
      weeks to document your sleeping habits. For the actigraphy you will be asked to wear a small&#xD;
      wrist-watch like device. This device will monitor and record your motion, and will also test&#xD;
      your sleep and wake periods. It may be worn for up to 2 weeks, 24 hours per day (except while&#xD;
      taking a shower).&#xD;
&#xD;
      If the results of the at-home actigraphy show that you are still able to take part in this&#xD;
      study, you will continue the final part of the screening procedure which is an inpatient&#xD;
      visit to conduct a sleep study. The following tests/procedures will be done for this final&#xD;
      screening visit: We will ask you to come into the sleep laboratory to sleep overnight (sleep&#xD;
      study). A technician will attach the leads (wires) to your body and you will need to keep&#xD;
      these leads on during the night. The attached wires will be connected to a machine to measure&#xD;
      chest and abdominal (stomach area) movements, airflow at your mouth and lips, blood oxygen&#xD;
      level, muscle tone, eye movements, heart rate and electrical activity of the brain. In the&#xD;
      morning, the technician will remove the attached wires.&#xD;
&#xD;
      If the exams, tests and procedures during the screening visits show that you can continue to&#xD;
      be in the study, you will have 2 inpatient visits and 2 outpatient clinical visits.&#xD;
&#xD;
      Before beginning the study, we will assign you to one of the two study groups described&#xD;
      below. Which one you are assigned to will be decided by chance (like tossing a coin) and you&#xD;
      will have a one in two chance of being in any one group. A computer program will place you in&#xD;
      one of the study groups.&#xD;
&#xD;
      GROUP 1: If you are assigned to group 1, then you will receive active drug during visit 1&#xD;
      (first inpatient visit) and placebo (inactive drug which is same as receiving no drug) during&#xD;
      visit 3 (second inpatient visit). GROUP 2: If you are assigned to group 2, then you will&#xD;
      receive placebo (inactive drug which is same as receiving no drug) during visit 1 (first&#xD;
      inpatient visit) and active drug for visit 3 (second inpatient visit).&#xD;
&#xD;
      Neither you nor your study doctor can choose the group you will be in. Neither your study&#xD;
      doctor or his staff nor you will know which study group or medicine you will be receiving.&#xD;
      However should a medical emergency occur, this information will be made immediately available&#xD;
      to your study doctor.&#xD;
&#xD;
      During the inpatient visit when you receive active drug, you will receive: Ketoconazole&#xD;
      pills. You will swallow these pills every 6 hours (4 times per day). Testosterone gel. You&#xD;
      will rub this gel into your skin once a day in the morning. Hydrocortisone pills. You will&#xD;
      swallow these pills 3 times a day.&#xD;
&#xD;
      During the inpatient visit when you receive placebo (inactive drug), you will receive:&#xD;
&#xD;
        -  Inactive placebo pills (looks like ketoconazole). You will swallow these pills every 6&#xD;
           hours (4 times per day).&#xD;
&#xD;
        -  Inactive placebo gel (looks like testosterone gel). You will rub this gel into your skin&#xD;
           once a day in the morning.&#xD;
&#xD;
        -  Inactive placebo pills (looks like hydrocortisone). You will swallow these pills 3 times&#xD;
           a day.&#xD;
&#xD;
      Night before First Inpatient Visit Before coming to the CTRC for your first inpatient visit,&#xD;
      you will be asked to sleep 10 hours for two consecutive nights (from 10 PM to 8 AM) at home.&#xD;
      During your sleep, you will be wearing an actiwatch to monitor your sleep at home. You cannot&#xD;
      drink any alcohol during this 2 day period. We will send you a text message or telephone you&#xD;
      to remind you to sleep during these times and not to drink alcohol. The inpatient study visit&#xD;
      will be cancelled if you didn't have enough sleep at home or if you consumed alcohol.&#xD;
&#xD;
      Study Visit 1 (First Inpatient) For this visit we will ask you to arrive at the CTRC no later&#xD;
      than 5 PM on the first day. We will allow you to go home sometime after lunch after the 5th&#xD;
      night. We will give you breakfast, lunch and dinner at set times while you are in the CTRC.&#xD;
      The meals are standard, so that what you may have eaten before will not interfere with the&#xD;
      study results. The following tests/procedures will be done at this visit: We will download&#xD;
      the information from your actiwatch to verify your sleep at home. We will be putting external&#xD;
      leads on your body, as occurred during the sleep study, so that we can continuously check&#xD;
      your sleep EEG, actiwatch activity and heart rate. We will expose you to dim light (this is&#xD;
      so we can measure your &quot;body clock&quot;). From 7 PM until your bedtime every night, saliva will&#xD;
      be collected hourly so we can measure your &quot;body clock&quot;. We will ask you to fill out a short&#xD;
      questionnaire to measure how sleepy you are, how hungry you are and do a computerized test of&#xD;
      cognitive function every 2 hours (on odd, not even, hours). This will take about 5 minutes.&#xD;
      Starting at 8PM on your first night, urine will collected until 8AM of the following day.&#xD;
      This will be repeated every 12-hour period whilst in-lab for measurements of components of in&#xD;
      the urine. We will give you an Oral Glucose Tolerance Test (OGTT) in the morning of the first&#xD;
      and last days (on two occasions) while you are in the CTRC. The OGTT is the test that&#xD;
      measures the body's ability to use a type of sugar, called glucose, which is the body's main&#xD;
      source of energy.&#xD;
&#xD;
        -  Before the test begins, we will insert a cannula into a vein in your arm and a sample of&#xD;
           blood will be taken. The cannula is a small plastic tube through which we will sample&#xD;
           your blood. It is inserted over a metal needle into your vein. The metal needle is&#xD;
           removed once the cannula is in place.&#xD;
&#xD;
        -  We will ask you to drink a liquid that is high in glucose (75 grams).&#xD;
&#xD;
        -  In the first hour, we will draw about 5ml (1 teaspoon) of blood will be taken from the&#xD;
           cannula every 5 minutes.&#xD;
&#xD;
        -  In the second hour, about 5ml (1 teaspoon) of blood will be taken from the cannula every&#xD;
           10 minutes&#xD;
&#xD;
        -  In the third hour, about 5ml (1teaspoon) of blood will be taken from the cannula every&#xD;
           20 minutes.&#xD;
&#xD;
        -  We will draw an additional 10ml (2 teaspoons) of blood to measure inflammation,&#xD;
           hormones, gene expression, and bone metabolism&#xD;
&#xD;
        -  The entire test will take about 3 hours.&#xD;
&#xD;
      We will give you an opportunity to sleep before we discharge you and we will test you for&#xD;
      sleepiness. Arrangements will be made for you to be driven home if necessary. During this&#xD;
      time you cannot drink caffeinated drinks, or use nicotine products.&#xD;
&#xD;
      Study Visit 2 (First Outpatient) This visit will take place one week after you are discharged&#xD;
      from your first inpatient visit. At this visit we will ask you about any side effects and&#xD;
      draw about 1 tablespoon of blood for complete blood count and routine chemistry check,&#xD;
      including liver function tests.&#xD;
&#xD;
      Study Visit 3 (Second Inpatient) This visit will take place one week after your first&#xD;
      outpatient visit (about 2 weeks after your first inpatient visit). This visit is identical&#xD;
      the first inpatient study Visit 1. For this visit, if you received active study drug during&#xD;
      your first inpatient visit, you will receive a placebo. If you received the placebo during&#xD;
      the first inpatient study Visit 1, then you will receive active study drug during this visit.&#xD;
&#xD;
      Study Visit 4 (Second Outpatient) This visit will take place one week after you are&#xD;
      discharged from your second inpatient visit. At this visit we will ask you about any side&#xD;
      effects and draw about 1 tablespoon of blood for complete blood count and routine chemistry&#xD;
      check, including liver function tests.&#xD;
&#xD;
      All visits A total of about half a pint (16 tablespoons) of blood will be collected for this&#xD;
      study. We will collect less than what you would donate to the blood bank.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">October 2023</completion_date>
  <primary_completion_date type="Actual">November 2017</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Insulin Sensitivity</measure>
    <time_frame>3 years</time_frame>
    <description>Insulin sensitivity determined by minimal model of a frequently sampled oral glucose tolerance test (OGTT).This method is extensively validated, and previously utilized by us.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disposition index</measure>
    <time_frame>3 years</time_frame>
    <description>Disposition index (determined by minimal model of the same OGTT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-peptide glucose dose-response</measure>
    <time_frame>3 years</time_frame>
    <description>C-peptide glucose dose-response (also calculated from the same OGTT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lapses on Psychomotor Vigilance Task</measure>
    <time_frame>3 years</time_frame>
    <description>Measure of psychomotor performance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Karolinska Sleepiness Scale</measure>
    <time_frame>3 years</time_frame>
    <description>Measures sleepiness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urinary Catecholamines</measure>
    <time_frame>3 years</time_frame>
    <description>Measures sympathetic/parasympathetic activity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart Rate Variability</measure>
    <time_frame>3 years</time_frame>
    <description>Measures sympathetic/parasympathetic activity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Free Fatty Acid Concentrations</measure>
    <time_frame>3 years</time_frame>
    <description>Measures potential mediator of insulin resistance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory marker panel</measure>
    <time_frame>3 years</time_frame>
    <description>blood interleukin-6, sTNFr2, IL1ra, CRP, NFkB concentrations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Computerized cognitive testing</measure>
    <time_frame>3 years</time_frame>
    <description>Two card gambling task, modified Sternberg working memory task</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone turnover panel</measure>
    <time_frame>3 years</time_frame>
    <description>P1NP (bone formation marker) and NTX (bone resorption marker)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Food cravings,</measure>
    <time_frame>3 years</time_frame>
    <description>Food Craving Index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of mood states.</measure>
    <time_frame>3 years</time_frame>
    <description>Profile of Mood States (POMS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Food intake</measure>
    <time_frame>3 years</time_frame>
    <description>meal and snack consumption calculation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hunger measurement</measure>
    <time_frame>3 years</time_frame>
    <description>Flint visual analogue scale</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Epigenetics</measure>
    <time_frame>3 years</time_frame>
    <description>Explorative study</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Insulin Resistance</condition>
  <arm_group>
    <arm_group_label>Placebo and Drug Group 2</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo pills and gel is used in place. Placebo for Ketoconazole is taken 4 times a day Placebo for Hydrocortisone is taken 3 times a day Placebo for testosterone gel is applied once a day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Drug and Placebo Group 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ketoconazole is taken 4 times a day Hydrocortisone is taken 3 times a day Testosterone gel is applied once a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketoconazole</intervention_name>
    <description>Ketoconazole is taken 4 times a day</description>
    <arm_group_label>Drug and Placebo Group 1</arm_group_label>
    <arm_group_label>Placebo and Drug Group 2</arm_group_label>
    <other_name>Nizoral</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydrocortisone</intervention_name>
    <description>Hydrocortisone is taken 3 times a day</description>
    <arm_group_label>Drug and Placebo Group 1</arm_group_label>
    <arm_group_label>Placebo and Drug Group 2</arm_group_label>
    <other_name>Cortef, Cortril, Hydrocortone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Testosterone</intervention_name>
    <description>Testosterone gel is applied once a day</description>
    <arm_group_label>Drug and Placebo Group 1</arm_group_label>
    <arm_group_label>Placebo and Drug Group 2</arm_group_label>
    <other_name>AndroGel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for ketoconazole</intervention_name>
    <description>Placebo for ketoconazole</description>
    <arm_group_label>Drug and Placebo Group 1</arm_group_label>
    <arm_group_label>Placebo and Drug Group 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for hydrocortisone</intervention_name>
    <description>Placebo for hydrocortisone</description>
    <arm_group_label>Drug and Placebo Group 1</arm_group_label>
    <arm_group_label>Placebo and Drug Group 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for testosterone</intervention_name>
    <description>Placebo for testosterone</description>
    <arm_group_label>Drug and Placebo Group 1</arm_group_label>
    <arm_group_label>Placebo and Drug Group 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men aged 22-45 years&#xD;
&#xD;
          -  Willingness to provide written informed consent&#xD;
&#xD;
          -  Stable weight over preceding 6 weeks&#xD;
&#xD;
          -  Body Mass index (BMI) 20-28 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable or unwilling to provide IRB-approved informed consent&#xD;
&#xD;
          -  Clinical disorders and/or illnesses&#xD;
&#xD;
          -  Current medical or drug treatment, as assessed by questionnaire&#xD;
&#xD;
          -  History of brain injury or of learning disability&#xD;
&#xD;
          -  Vision or hearing impairment unless corrected back to normal&#xD;
&#xD;
          -  Anemia (Hct &lt;38%)&#xD;
&#xD;
          -  History of psychiatric illness&#xD;
&#xD;
          -  Clinically significant abnormalities in blood and urine, and free of traces of drugs&#xD;
             Other endocrine abnormalities including hypothyroidism or adrenal failure; primary&#xD;
             gonadal disease as indicated by serum LH or FSH concentration &gt;10 or &gt;15 IU/L,&#xD;
             respectively, hyperprolactinemia indicated by prolactin &gt;25ug/L&#xD;
&#xD;
          -  Type 2 Diabetes (HgbA1C)&#xD;
&#xD;
          -  Current smoker&#xD;
&#xD;
          -  Recent or concurrent drug or alcohol abuse&#xD;
&#xD;
          -  Blood donation in previous eight weeks&#xD;
&#xD;
          -  Travel across time zones within one month of entering the study&#xD;
&#xD;
          -  Sleep or circadian disorder&#xD;
&#xD;
          -  Shift work within three months of entering the study&#xD;
&#xD;
          -  Irregular bedtimes (not between 6 and 10 hours in duration)&#xD;
&#xD;
          -  Unoperated obstructive uropathy, recurrent prostatitis, indeterminate prostatic&#xD;
             nodularity, Hx or Suspicion of cancer of the prostate gland or PSA &gt;4ng/ml&#xD;
&#xD;
          -  Previous adverse reaction to sleep deprivation or any of the drugs to be administered&#xD;
&#xD;
          -  Concurrent participation in another research study&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter Y Liu, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Los Angeles Biomedical Research Institute</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90509</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>O'Byrne NA, Yuen F, Niaz W, Liu PY. Sleep and the Testis. Curr Opin Endocr Metab Res. 2021 Jun;18:83-93. doi: 10.1016/j.coemr.2021.03.002. Epub 2021 Mar 11.</citation>
    <PMID>33937581</PMID>
  </reference>
  <reference>
    <citation>O'Byrne NA, Yuen F, Butt WZ, Liu PY. Sleep and Circadian Regulation of Cortisol: A Short Review. Curr Opin Endocr Metab Res. 2021 Jun;18:178-186. doi: 10.1016/j.coemr.2021.03.011. Epub 2021 May 5.</citation>
    <PMID>35128146</PMID>
  </reference>
  <results_reference>
    <citation>Liu PY, Lawrence-Sidebottom D, Piotrowska K, Zhang W, Iranmanesh A, Auchus RJ, Veldhuis JD, Van Dongen HPA. Clamping Cortisol and Testosterone Mitigates the Development of Insulin Resistance during Sleep Restriction in Men. J Clin Endocrinol Metab. 2021 Aug 18;106(9):e3436-e3448. doi: 10.1210/clinem/dgab375.</citation>
    <PMID>34043794</PMID>
  </results_reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>September 22, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 6, 2014</study_first_posted>
  <last_update_submitted>April 5, 2023</last_update_submitted>
  <last_update_submitted_qc>April 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sleep Restriction</keyword>
  <keyword>Insulin Resistance</keyword>
  <keyword>Testosterone</keyword>
  <keyword>Cortisol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketoconazole</mesh_term>
    <mesh_term>Hydrocortisone</mesh_term>
    <mesh_term>Hydrocortisone 17-butyrate 21-propionate</mesh_term>
    <mesh_term>Hydrocortisone acetate</mesh_term>
    <mesh_term>Hydrocortisone hemisuccinate</mesh_term>
    <mesh_term>Methyltestosterone</mesh_term>
    <mesh_term>Testosterone</mesh_term>
    <mesh_term>Testosterone undecanoate</mesh_term>
    <mesh_term>Testosterone enanthate</mesh_term>
    <mesh_term>Testosterone 17 beta-cypionate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02256865
org study id: 30068-01
nct id: NCT02256865
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to study the effects of sleep restriction on the production of
      two hormones, cortisol and testosterone. The investigators aim to show that changing these
      hormones leads to insulin resistance, which is an important cause of type 2 diabetes
      mellitus. The investigators may also study the effect of sleep restriction on your food
      intake and cravings, mood, inflammation, metabolism (including bone), and other hormones.
      Inflammation is your body's response to stress and injury. Bone metabolism is a process of
      how your body regenerates (renews) new bone cells and removes old bone cells. Hormones are
      natural substances (materials) that are produced in the body and that influences (effects)
      the way the body grows or develops.
Screening Visits

        -  To see if you are able to take part in this study, you will first have an outpatient
           visit at the CTRC (Clinical and Translational Research Center). This visit will take
           about 90 minutes.

        -  The following tests/procedures will be done at this visit:

             -  We will ask you about your medical history and past health

             -  We will give you a physical examination (including digital rectal examination of
                the prostate gland if you are over the age of 40)

             -  We will ask you to answer sleep, mood and general health screening questionnaires.

             -  We will ask you to complete a questionnaire to help us understand how testosterone
                and other hormones control sexual function and drive.

             -  We will draw about 1 tablespoon of blood from a needle placed in a vein in your arm
                for routine safety tests and to check to see if you have any hormonal problems.

             -  We will give you an ECG (recording of heartbeat). For this test we will attach
                12-lead sensors to your chest.

             -  We will collect urine sample from you for a drug screening test.

             -  A dietitian will review meal plans for the inpatient stay (Study Visit 1 and 3
                only).

      If the first screening visit shows that you are able to continue to take part in this study,
      you will continue the screening part of the study at home. The following will be done at
      home: We will ask you to undergo an at-home actigraphy and keep a daily sleep diary for two
      weeks to document your sleeping habits. For the actigraphy you will be asked to wear a small
      wrist-watch like device. This device will monitor and record your motion, and will also test
      your sleep and wake periods. It may be worn for up to 2 weeks, 24 hours per day (except while
      taking a shower).

      If the results of the at-home actigraphy show that you are still able to take part in this
      study, you will continue the final part of the screening procedure which is an inpatient
      visit to conduct a sleep study. The following tests/procedures will be done for this final
      screening visit: We will ask you to come into the sleep laboratory to sleep overnight (sleep
      study). A technician will attach the leads (wires) to your body and you will need to keep
      these leads on during the night. The attached wires will be connected to a machine to measure
      chest and abdominal (stomach area) movements, airflow at your mouth and lips, blood oxygen
      level, muscle tone, eye movements, heart rate and electrical activity of the brain. In the
      morning, the technician will remove the attached wires.

      If the exams, tests and procedures during the screening visits show that you can continue to
      be in the study, you will have 2 inpatient visits and 2 outpatient clinical visits.

      Before beginning the study, we will assign you to one of the two study groups described
      below. Which one you are assigned to will be decided by chance (like tossing a coin) and you
      will have a one in two chance of being in any one group. A computer program will place you in
      one of the study groups.

      GROUP 1: If you are assigned to group 1, then you will receive active drug during visit 1
      (first inpatient visit) and placebo (inactive drug which is same as receiving no drug) during
      visit 3 (second inpatient visit). GROUP 2: If you are assigned to group 2, then you will
      receive placebo (inactive drug which is same as receiving no drug) during visit 1 (first
      inpatient visit) and active drug for visit 3 (second inpatient visit).

      Neither you nor your study doctor can choose the group you will be in. Neither your study
      doctor or his staff nor you will know which study group or medicine you will be receiving.
      However should a medical emergency occur, this information will be made immediately available
      to your study doctor.

      During the inpatient visit when you receive active drug, you will receive: Ketoconazole
      pills. You will swallow these pills every 6 hours (4 times per day). Testosterone gel. You
      will rub this gel into your skin once a day in the morning. Hydrocortisone pills. You will
      swallow these pills 3 times a day.

      During the inpatient visit when you receive placebo (inactive drug), you will receive:

        -  Inactive placebo pills (looks like ketoconazole). You will swallow these pills every 6
           hours (4 times per day).

        -  Inactive placebo gel (looks like testosterone gel). You will rub this gel into your skin
           once a day in the morning.

        -  Inactive placebo pills (looks like hydrocortisone). You will swallow these pills 3 times
           a day.

      Night before First Inpatient Visit Before coming to the CTRC for your first inpatient visit,
      you will be asked to sleep 10 hours for two consecutive nights (from 10 PM to 8 AM) at home.
      During your sleep, you will be wearing an actiwatch to monitor your sleep at home. You cannot
      drink any alcohol during this 2 day period. We will send you a text message or telephone you
      to remind you to sleep during these times and not to drink alcohol. The inpatient study visit
      will be cancelled if you didn't have enough sleep at home or if you consumed alcohol.

      Study Visit 1 (First Inpatient) For this visit we will ask you to arrive at the CTRC no later
      than 5 PM on the first day. We will allow you to go home sometime after lunch after the 5th
      night. We will give you breakfast, lunch and dinner at set times while you are in the CTRC.
      The meals are standard, so that what you may have eaten before will not interfere with the
      study results. The following tests/procedures will be done at this visit: We will download
      the information from your actiwatch to verify your sleep at home. We will be putting external
      leads on your body, as occurred during the sleep study, so that we can continuously check
      your sleep EEG, actiwatch activity and heart rate. We will expose you to dim light (this is
      so we can measure your "body clock"). From 7 PM until your bedtime every night, saliva will
      be collected hourly so we can measure your "body clock". We will ask you to fill out a short
      questionnaire to measure how sleepy you are, how hungry you are and do a computerized test of
      cognitive function every 2 hours (on odd, not even, hours). This will take about 5 minutes.
      Starting at 8PM on your first night, urine will collected until 8AM of the following day.
      This will be repeated every 12-hour period whilst in-lab for measurements of components of in
      the urine. We will give you an Oral Glucose Tolerance Test (OGTT) in the morning of the first
      and last days (on two occasions) while you are in the CTRC. The OGTT is the test that
      measures the body's ability to use a type of sugar, called glucose, which is the body's main
      source of energy.

        -  Before the test begins, we will insert a cannula into a vein in your arm and a sample of
           blood will be taken. The cannula is a small plastic tube through which we will sample
           your blood. It is inserted over a metal needle into your vein. The metal needle is
           removed once the cannula is in place.

        -  We will ask you to drink a liquid that is high in glucose (75 grams).

        -  In the first hour, we will draw about 5ml (1 teaspoon) of blood will be taken from the
           cannula every 5 minutes.

        -  In the second hour, about 5ml (1 teaspoon) of blood will be taken from the cannula every
           10 minutes

        -  In the third hour, about 5ml (1teaspoon) of blood will be taken from the cannula every
           20 minutes.

        -  We will draw an additional 10ml (2 teaspoons) of blood to measure inflammation,
           hormones, gene expression, and bone metabolism

        -  The entire test will take about 3 hours.

      We will give you an opportunity to sleep before we discharge you and we will test you for
      sleepiness. Arrangements will be made for you to be driven home if necessary. During this
      time you cannot drink caffeinated drinks, or use nicotine products.

      Study Visit 2 (First Outpatient) This visit will take place one week after you are discharged
      from your first inpatient visit. At this visit we will ask you about any side effects and
      draw about 1 tablespoon of blood for complete blood count and routine chemistry check,
      including liver function tests.

      Study Visit 3 (Second Inpatient) This visit will take place one week after your first
      outpatient visit (about 2 weeks after your first inpatient visit). This visit is identical
      the first inpatient study Visit 1. For this visit, if you received active study drug during
      your first inpatient visit, you will receive a placebo. If you received the placebo during
      the first inpatient study Visit 1, then you will receive active study drug during this visit.

      Study Visit 4 (Second Outpatient) This visit will take place one week after you are
      discharged from your second inpatient visit. At this visit we will ask you about any side
      effects and draw about 1 tablespoon of blood for complete blood count and routine chemistry
      check, including liver function tests.

      All visits A total of about half a pint (16 tablespoons) of blood will be collected for this
      study. We will collect less than what you would donate to the blood bank.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Insulin Sensitivity
time frame: 3 years
description: Insulin sensitivity determined by minimal model of a frequently sampled oral glucose tolerance test (OGTT).This method is extensively validated, and previously utilized by us.
measure: Disposition index
time frame: 3 years
description: Disposition index (determined by minimal model of the same OGTT)
measure: C-peptide glucose dose-response
time frame: 3 years
description: C-peptide glucose dose-response (also calculated from the same OGTT)
measure: Lapses on Psychomotor Vigilance Task
time frame: 3 years
description: Measure of psychomotor performance
measure: Karolinska Sleepiness Scale
time frame: 3 years
description: Measures sleepiness
measure: Urinary Catecholamines
time frame: 3 years
description: Measures sympathetic/parasympathetic activity
measure: Heart Rate Variability
time frame: 3 years
description: Measures sympathetic/parasympathetic activity
measure: Free Fatty Acid Concentrations
time frame: 3 years
description: Measures potential mediator of insulin resistance
measure: Inflammatory marker panel
time frame: 3 years
description: blood interleukin-6, sTNFr2, IL1ra, CRP, NFkB concentrations
measure: Computerized cognitive testing
time frame: 3 years
description: Two card gambling task, modified Sternberg working memory task
measure: Bone turnover panel
time frame: 3 years
description: P1NP (bone formation marker) and NTX (bone resorption marker)
measure: Food cravings,
time frame: 3 years
description: Food Craving Index
measure: Assessment of mood states.
time frame: 3 years
description: Profile of Mood States (POMS)
measure: Food intake
time frame: 3 years
description: meal and snack consumption calculation
measure: Hunger measurement
time frame: 3 years
description: Flint visual analogue scale
measure: Epigenetics
time frame: 3 years
description: Explorative study
arm group label: Placebo and Drug Group 2
arm group type: Placebo Comparator
description: Placebo pills and gel is used in place. Placebo for Ketoconazole is taken 4 times a day Placebo for Hydrocortisone is taken 3 times a day Placebo for testosterone gel is applied once a day.
arm group label: Drug and Placebo Group 1
arm group type: Active Comparator
description: Ketoconazole is taken 4 times a day Hydrocortisone is taken 3 times a day Testosterone gel is applied once a day
intervention type: Drug
intervention name: Ketoconazole
description: Ketoconazole is taken 4 times a day
arm group label: Drug and Placebo Group 1
arm group label: Placebo and Drug Group 2
other name: Nizoral
intervention type: Drug
intervention name: Hydrocortisone
description: Hydrocortisone is taken 3 times a day
arm group label: Drug and Placebo Group 1
arm group label: Placebo and Drug Group 2
other name: Cortef, Cortril, Hydrocortone
intervention type: Drug
intervention name: Testosterone
description: Testosterone gel is applied once a day
arm group label: Drug and Placebo Group 1
arm group label: Placebo and Drug Group 2
other name: AndroGel
intervention type: Drug
intervention name: Placebo for ketoconazole
description: Placebo for ketoconazole
arm group label: Drug and Placebo Group 1
arm group label: Placebo and Drug Group 2
intervention type: Drug
intervention name: Placebo for hydrocortisone
description: Placebo for hydrocortisone
arm group label: Drug and Placebo Group 1
arm group label: Placebo and Drug Group 2
intervention type: Drug
intervention name: Placebo for testosterone
description: Placebo for testosterone
arm group label: Drug and Placebo Group 1
arm group label: Placebo and Drug Group 2
criteria: 
gender: Male
minimum age: 22 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Peter Y Liu, MD PhD
role: Principal Investigator
affiliation: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
facility: 
country: United States
citation: O'Byrne NA, Yuen F, Niaz W, Liu PY. Sleep and the Testis. Curr Opin Endocr Metab Res. 2021 Jun;18:83-93. doi: 10.1016/j.coemr.2021.03.002. Epub 2021 Mar 11.
PMID: 33937581
citation: O'Byrne NA, Yuen F, Butt WZ, Liu PY. Sleep and Circadian Regulation of Cortisol: A Short Review. Curr Opin Endocr Metab Res. 2021 Jun;18:178-186. doi: 10.1016/j.coemr.2021.03.011. Epub 2021 May 5.
PMID: 35128146
citation: Liu PY, Lawrence-Sidebottom D, Piotrowska K, Zhang W, Iranmanesh A, Auchus RJ, Veldhuis JD, Van Dongen HPA. Clamping Cortisol and Testosterone Mitigates the Development of Insulin Resistance during Sleep Restriction in Men. J Clin Endocrinol Metab. 2021 Aug 18;106(9):e3436-e3448. doi: 10.1210/clinem/dgab375.
PMID: 34043794
responsible party type: Sponsor
mesh term: Insulin Resistance
mesh term: Ketoconazole
mesh term: Hydrocortisone
mesh term: Hydrocortisone 17-butyrate 21-propionate
mesh term: Hydrocortisone acetate
mesh term: Hydrocortisone hemisuccinate
mesh term: Methyltestosterone
mesh term: Testosterone
mesh term: Testosterone undecanoate
mesh term: Testosterone enanthate
mesh term: Testosterone 17 beta-cypionate
sharing ipd: Undecided