<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/NCT03228732</url>
  </required_header>
  <id_info>
    <org_study_id>HP-00075896</org_study_id>
    <nct_id>NCT03228732</nct_id>
  </id_info>
  <brief_title>The Effects of Fluoxetine and/or DHEA</brief_title>
  <official_title>The Effects of the Selective Serotonin Reuptake Inhibitor, Fluoxetine and/or DHEA, on Neuroendocrine, Autonomic Nervous System and Metabolic Counterregulatory Responses During Repeated Hypoglycemia in T1DM Individuals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Maryland, Baltimore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Maryland, Baltimore</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>
      (1) To determine how the Selective Serotonin Reuptake Inhibitor (SSRI), fluoxetine (Prozac),&#xD;
      an antidepressant often used to treat depression, stimulates the participant's body's ability&#xD;
      to defend against low blood sugar (hypoglycemia). (2) To learn how a hormone,&#xD;
      dehydroepiandrosterone (DHEA), stimulates the participant's body's ability to defend itself&#xD;
      from low blood sugar (hypoglycemia). DHEA is a hormone produced naturally in the human body.&#xD;
      However, it can be manufactured and is sold as an over-the-counter dietary supplement. The&#xD;
      dose the investigators are giving in this study is higher than the usual recommended dosage&#xD;
      taken as a supplement for certain medical conditions. (3) To study combined effects of&#xD;
      fluoxetine and DHEA during low blood glucose. In the present study, the investigators will&#xD;
      measure the participant's body's responses to hypoglycemia when given fluoxetine or DHEA or&#xD;
      fluoxetine and DHEA or a placebo (a pill with no fluoxetine or DHEA). Approximately 64&#xD;
      individuals with type 1 diabetes will take part in this study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 19, 2017</start_date>
  <completion_date type="Anticipated">December 15, 2025</completion_date>
  <primary_completion_date type="Anticipated">February 15, 2024</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>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants will be randomized into 2 groups. Group 1 will consist of a random order of Protocol 1 and Protocol 5. Group 2 will consist of a randomized order of Protocols 2, 3, 4</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the level of catecholamines in plasma</measure>
    <time_frame>An average of 3 years</time_frame>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Type 1 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Placebo 1</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Visit 1:&#xD;
Study Day 1: Hyperinsulinemia/ euglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with placebo&#xD;
Visit 2:&#xD;
same as visit 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo 2</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Visit 1:&#xD;
Study Day 1: Hyperinsulinemia/ hypoglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with placebo&#xD;
Visit 2:&#xD;
same as visit 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fluoxetine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Visit 1:&#xD;
Study Day 1: Hyperinsulinemia/ hypoglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with fluoxetine&#xD;
Visit 2:&#xD;
same as visit 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DHEA</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Visit 1:&#xD;
Study Day 1: Hyperinsulinemia/ hypoglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with DHEA&#xD;
Visit 2:&#xD;
same as visit 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fluoxetine and DHEA</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Visit 1:&#xD;
Study Day 1: Hyperinsulinemia/ hypoglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with fluoxetine and DHEA&#xD;
Visit 2:&#xD;
same as visit 1</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>There will be two 2-day inpatient visits with 8-weeks of treatment with placebo between those visits.</description>
    <arm_group_label>Placebo 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>There will be two 2-day inpatient visits with 8-weeks of treatment with placebo between those visits.</description>
    <arm_group_label>Placebo 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluoxetine</intervention_name>
    <description>There will be two 2-day inpatient visits with 8-weeks of treatment with fluoxetine between those visits.</description>
    <arm_group_label>Fluoxetine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DHEA</intervention_name>
    <description>There will be two 2-day inpatient visits with 8-weeks of treatment with DHEA between those visits.</description>
    <arm_group_label>DHEA</arm_group_label>
    <other_name>dehydroepiandrosterone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluoxetine and DHEA</intervention_name>
    <description>There will be two 2-day inpatient visits with 8-weeks of treatment with fluoxetine and DHEA between those visits.</description>
    <arm_group_label>Fluoxetine and DHEA</arm_group_label>
    <other_name>Prozac, dehydroepiandrosterone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  64 (32 males, 32 females) T1DM patients aged 18-50 yr.&#xD;
&#xD;
          -  HbA1c &lt; 11.0%&#xD;
&#xD;
          -  No clinically diagnosed diabetic tissue complications (i.e. history of retinopathy,&#xD;
             neuropathy, stasis ulcers, etc)&#xD;
&#xD;
          -  Body mass index &lt; 40kg · m-2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Subjects unable to give voluntary informed consent&#xD;
&#xD;
          -  Subjects on anticoagulant drugs, anemic or with known bleeding diatheses&#xD;
&#xD;
          -  Subjects taking any of the following medications will be excluded: Non-selective Beta&#xD;
             Blockers, Sedative-Hypnotics, Anticonvulsants, Antiparkinsonian drugs, Antipsychotics,&#xD;
             Antidepressants, Mood stabilizers, CNS Stimulants, Opioids, Hallucinogens&#xD;
&#xD;
          -  Subjects with a recent medical illness or past history of severe depression, mania or&#xD;
             psychotic disease&#xD;
&#xD;
          -  Subjects that score greater than 50 on the depression scale&#xD;
&#xD;
          -  Subjects unwillingness or inability to comply with approved contraception measures&#xD;
&#xD;
          -  Abnormal results following screening tests and physical examination that are&#xD;
             clinically significant&#xD;
&#xD;
          -  Subjects with a history of severe uncontrolled hypertension (i.e., blood pressure&#xD;
             greater than 160/100), heart disease, cerebrovascular incidents&#xD;
&#xD;
          -  Clinically significant cardiac abnormalities (e.g. heart failure, arrhythmias,&#xD;
             ischemic tachycardia, S-T segment deviations, etc.) from history or from cardiac&#xD;
             stress testing in subjects ≥ 40 years old.&#xD;
&#xD;
          -  Pneumonia&#xD;
&#xD;
          -  Hepatic Failure/Jaundice&#xD;
&#xD;
          -  Creatinine greater than 1.6 mg/dl&#xD;
&#xD;
          -  Acute Cerebrovascular/ Neurological deficit&#xD;
&#xD;
          -  Fever greater than 38 °C&#xD;
&#xD;
        Screening Laboratory Tests Exclusion Criteria&#xD;
&#xD;
          -  Hematocrit lower than 32&#xD;
&#xD;
          -  WBC lower than 3 thou/ul or greater than 14 thou/ul&#xD;
&#xD;
          -  Liver Function Tests: SGOT and SGPT greater than twice upper limit of normal range&#xD;
             (i.e. greater than 80 U/L).&#xD;
&#xD;
          -  TBil greater than 2 mg/dl&#xD;
&#xD;
          -  Alkaline Phosphatase greater than 150U/L&#xD;
&#xD;
          -  Positive HIV, Hep B, Hep C&#xD;
&#xD;
          -  Hepatic transaminase &gt; 2x normal&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephen N Davis, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Maryland, Baltimore</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Maka Siamashvili, MD</last_name>
    <phone>410-706-5623</phone>
    <email>msiamashvili@som.umaryland.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Vanessa Briscoe, PhD</last_name>
    <email>vbriscoe@som.umaryland.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Maryland</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maka Siamashvili, MD</last_name>
      <phone>410-706-5623</phone>
      <email>msiamashvili@som.umaryland.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 20, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <last_update_submitted>February 10, 2023</last_update_submitted>
  <last_update_submitted_qc>February 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Maryland, Baltimore</investigator_affiliation>
    <investigator_full_name>Stephen N. Davis, MBBS</investigator_full_name>
    <investigator_title>Chairman of Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluoxetine</mesh_term>
    <mesh_term>Dehydroepiandrosterone</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/NCT03228732
org study id: HP-00075896
nct id: NCT03228732
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
(1) To determine how the Selective Serotonin Reuptake Inhibitor (SSRI), fluoxetine (Prozac),
      an antidepressant often used to treat depression, stimulates the participant's body's ability
      to defend against low blood sugar (hypoglycemia). (2) To learn how a hormone,
      dehydroepiandrosterone (DHEA), stimulates the participant's body's ability to defend itself
      from low blood sugar (hypoglycemia). DHEA is a hormone produced naturally in the human body.
      However, it can be manufactured and is sold as an over-the-counter dietary supplement. The
      dose the investigators are giving in this study is higher than the usual recommended dosage
      taken as a supplement for certain medical conditions. (3) To study combined effects of
      fluoxetine and DHEA during low blood glucose. In the present study, the investigators will
      measure the participant's body's responses to hypoglycemia when given fluoxetine or DHEA or
      fluoxetine and DHEA or a placebo (a pill with no fluoxetine or DHEA). Approximately 64
      individuals with type 1 diabetes will take part in this study.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be randomized into 2 groups. Group 1 will consist of a random order of Protocol 1 and Protocol 5. Group 2 will consist of a randomized order of Protocols 2, 3, 4
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Change in the level of catecholamines in plasma
time frame: An average of 3 years
arm group label: Placebo 1
arm group type: Placebo Comparator
description: Visit 1:
Study Day 1: Hyperinsulinemia/ euglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with placebo
Visit 2:
same as visit 1
arm group label: Placebo 2
arm group type: Placebo Comparator
description: Visit 1:
Study Day 1: Hyperinsulinemia/ hypoglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with placebo
Visit 2:
same as visit 1
arm group label: Fluoxetine
arm group type: Active Comparator
description: Visit 1:
Study Day 1: Hyperinsulinemia/ hypoglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with fluoxetine
Visit 2:
same as visit 1
arm group label: DHEA
arm group type: Active Comparator
description: Visit 1:
Study Day 1: Hyperinsulinemia/ hypoglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with DHEA
Visit 2:
same as visit 1
arm group label: Fluoxetine and DHEA
arm group type: Active Comparator
description: Visit 1:
Study Day 1: Hyperinsulinemia/ hypoglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with fluoxetine and DHEA
Visit 2:
same as visit 1
intervention type: Drug
intervention name: Placebo Oral Tablet
description: There will be two 2-day inpatient visits with 8-weeks of treatment with placebo between those visits.
arm group label: Placebo 1
intervention type: Drug
intervention name: Placebo Oral Tablet
description: There will be two 2-day inpatient visits with 8-weeks of treatment with placebo between those visits.
arm group label: Placebo 2
intervention type: Drug
intervention name: Fluoxetine
description: There will be two 2-day inpatient visits with 8-weeks of treatment with fluoxetine between those visits.
arm group label: Fluoxetine
intervention type: Drug
intervention name: DHEA
description: There will be two 2-day inpatient visits with 8-weeks of treatment with DHEA between those visits.
arm group label: DHEA
other name: dehydroepiandrosterone
intervention type: Drug
intervention name: Fluoxetine and DHEA
description: There will be two 2-day inpatient visits with 8-weeks of treatment with fluoxetine and DHEA between those visits.
arm group label: Fluoxetine and DHEA
other name: Prozac, dehydroepiandrosterone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Stephen N Davis, MBBS
role: Principal Investigator
affiliation: University of Maryland, Baltimore
last name: Maka Siamashvili, MD
phone: 410-706-5623
email: msiamashvili@som.umaryland.edu
last name: Vanessa Briscoe, PhD
email: vbriscoe@som.umaryland.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Maryland, Baltimore
investigator full name: Stephen N. Davis, MBBS
investigator title: Chairman of Medicine
mesh term: Diabetes Mellitus, Type 1
mesh term: Fluoxetine
mesh term: Dehydroepiandrosterone
sharing ipd: No