<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/NCT01672255</url>
  </required_header>
  <id_info>
    <org_study_id>HP-00044537; SSRI and Exercise</org_study_id>
    <nct_id>NCT01672255</nct_id>
  </id_info>
  <brief_title>Hypoglycemia Associated Autonomic Failure in Type 1 Diabetes Mellitus (DM)</brief_title>
  <official_title>Hypoglycemia Associated Autonomic Failure in Type 1 DM, SSRI and Exercise</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Maryland, Baltimore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Maryland, Baltimore</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Exercise is a cornerstone of diabetes management. It helps reduce blood pressure, promote&#xD;
      weight loss, lower insulin resistance and improve glucose and lipid (triglyceride and&#xD;
      HDL-cholesterol) profiles. Unfortunately, the benefits of exercise are often not embraced by&#xD;
      diabetic individuals because of the fear of low blood sugar (hypoglycemia). My laboratory has&#xD;
      demonstrated that Autonomic nervous system (ANS) counterregulatory failure plays an important&#xD;
      role in exercise associated hypoglycemia in Type 1 DM. ANS responses are significantly&#xD;
      reduced in Type 1 DM and are further blunted by antecedent episodes of hypoglycemia.&#xD;
      Furthermore, there is a large sexual dimorphism of reduced ANS responses during submaximal&#xD;
      exercise in both Type 1 DM and healthy individuals that is unexplained. Accumulating data are&#xD;
      demonstrating that serotonergic pathways can regulate ANS discharge. Generally, serotonergic&#xD;
      pathways are inhibitory but both single and longer term administration of selective serotonin&#xD;
      reuptake inhibitors (SSRI's) such as Prozac has been demonstrated to increase basal&#xD;
      epinephrine levels and enhance baroreflex control of Sympathetic nervous system (SNS)&#xD;
      activity. What is unknown is whether fluoxetine can also enhance SNS responses and also&#xD;
      override the large ANS sexual dimorphism present during sub maximal exercise. Therefore, the&#xD;
      purpose of this study is to determine if the SSRI fluoxetine (Prozac) can improve SNS&#xD;
      responses during exercise.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Catecholamines</measure>
    <time_frame>During 90 minute experimental period</time_frame>
    <description>This change in catecholamines will be compared to another 90 minute experimental period after 8 weeks administration of SSRI or placebo.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">64</enrollment>
  <condition>Type 1 Diabetes</condition>
  <condition>Hypoglycemia Associated Autonomic Failure</condition>
  <arm_group>
    <arm_group_label>Trial 1-SSRI</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>90 minute exercise baseline with 6 weeks treatment with SSRI (Prozac). Repeat 90 minute exercise after 6 week treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Trial 2-Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>90 minute exercise at baseline with 6 weeks treatment with placebo. Repeat 90 minute exercise after 6 weeks treatment of placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluoxetine</intervention_name>
    <description>20 mg week 1, 40 mg week 2, 60 mg week 3, 80 mg week 4-6</description>
    <arm_group_label>Trial 1-SSRI</arm_group_label>
    <other_name>Prozac</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo control</intervention_name>
    <description>20 mg Week 1, 40 mg Week 2, 60 mg Week 3, 80 mg Week 4-6</description>
    <arm_group_label>Trial 2-Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  32 (16 males, 16 females) Healthy controls aged 18-45 yr.&#xD;
&#xD;
          -  32 (16 males, 16 females) Type 1 diabetic patients aged 18-45 yr.&#xD;
&#xD;
          -  HbA1c 6-10.0%&#xD;
&#xD;
          -  Has been diagnosed Type 1 DM&#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;
          -  Pregnant women&#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&#xD;
&#xD;
          -  Subjects with a history of hypertension, heart disease, cerebrovascular incidents&#xD;
&#xD;
          -  Current tobacco use&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</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>
  <location>
    <facility>
      <name>University of Maryland, Baltimore</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>
    </contact>
    <investigator>
      <last_name>Stephen N. Davis, MBBS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>August 17, 2012</study_first_submitted>
  <study_first_submitted_qc>August 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 24, 2012</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>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>exercise</keyword>
  <keyword>diabetes</keyword>
  <keyword>SSRIs</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pure Autonomic Failure</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
    <mesh_term>Hypoglycemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluoxetine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01672255
org study id: HP-00044537; SSRI and Exercise
nct id: NCT01672255
lead sponsor: 
collaborator: 
has dmc: Yes
Exercise is a cornerstone of diabetes management. It helps reduce blood pressure, promote
      weight loss, lower insulin resistance and improve glucose and lipid (triglyceride and
      HDL-cholesterol) profiles. Unfortunately, the benefits of exercise are often not embraced by
      diabetic individuals because of the fear of low blood sugar (hypoglycemia). My laboratory has
      demonstrated that Autonomic nervous system (ANS) counterregulatory failure plays an important
      role in exercise associated hypoglycemia in Type 1 DM. ANS responses are significantly
      reduced in Type 1 DM and are further blunted by antecedent episodes of hypoglycemia.
      Furthermore, there is a large sexual dimorphism of reduced ANS responses during submaximal
      exercise in both Type 1 DM and healthy individuals that is unexplained. Accumulating data are
      demonstrating that serotonergic pathways can regulate ANS discharge. Generally, serotonergic
      pathways are inhibitory but both single and longer term administration of selective serotonin
      reuptake inhibitors (SSRI's) such as Prozac has been demonstrated to increase basal
      epinephrine levels and enhance baroreflex control of Sympathetic nervous system (SNS)
      activity. What is unknown is whether fluoxetine can also enhance SNS responses and also
      override the large ANS sexual dimorphism present during sub maximal exercise. Therefore, the
      purpose of this study is to determine if the SSRI fluoxetine (Prozac) can improve SNS
      responses during exercise.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in Catecholamines
time frame: During 90 minute experimental period
description: This change in catecholamines will be compared to another 90 minute experimental period after 8 weeks administration of SSRI or placebo.
arm group label: Trial 1-SSRI
arm group type: Active Comparator
description: 90 minute exercise baseline with 6 weeks treatment with SSRI (Prozac). Repeat 90 minute exercise after 6 week treatment.
arm group label: Trial 2-Placebo
arm group type: Placebo Comparator
description: 90 minute exercise at baseline with 6 weeks treatment with placebo. Repeat 90 minute exercise after 6 weeks treatment of placebo.
intervention type: Drug
intervention name: Fluoxetine
description: 20 mg week 1, 40 mg week 2, 60 mg week 3, 80 mg week 4-6
arm group label: Trial 1-SSRI
other name: Prozac
intervention type: Drug
intervention name: Placebo control
description: 20 mg Week 1, 40 mg Week 2, 60 mg Week 3, 80 mg Week 4-6
arm group label: Trial 2-Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
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
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Maryland, Baltimore
investigator full name: Stephen N. Davis, MBBS
investigator title: Principal Investigator
mesh term: Pure Autonomic Failure
mesh term: Diabetes Mellitus, Type 1
mesh term: Hypoglycemia
mesh term: Fluoxetine