<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/NCT01666964</url>
  </required_header>
  <id_info>
    <org_study_id>350758-12</org_study_id>
    <nct_id>NCT01666964</nct_id>
  </id_info>
  <brief_title>Hormone Deficiency After Brain Injury During Combat</brief_title>
  <official_title>Prevalence of Hypopituitarism Following Combat-related Traumatic Brain Injury in a Military Population</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Walter Reed National Military Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novo Nordisk A/S</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Walter Reed National Military Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      We would like to ascertain the prevalence of hypopituitarism after combat-related TBI. This&#xD;
      will lead to enhanced awareness, recognition, and treatment of hypopituitarism, which can&#xD;
      have life-saving ramifications and enhance quality of life and rehabilitation efforts in our&#xD;
      combat veterans.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The prevalence of hypopituitarism after combat-related traumatic brain injury (TBI) is&#xD;
      currently unknown. Recent civilian data on TBI show the prevalence of any pituitary hormone&#xD;
      deficiency is as high as 80% after 12 months. While the military prevalence of&#xD;
      hypopituitarism can be extrapolated from civilian data, a major limitation is the notably&#xD;
      different mechanism of injury (i.e., blast) for military personnel compared to civilians&#xD;
      (i.e., assaults, traffic accidents and falls). Little is known about the effect of shockwaves&#xD;
      from a blast injury on central nervous system tissue, and due to the unique nature of&#xD;
      blast-related TBI, the prevalence of pituitary dysfunction in affected service members may&#xD;
      significantly differ from nonmilitary subjects in prior studies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>October 2012</start_date>
  <completion_date type="Anticipated">May 2015</completion_date>
  <primary_completion_date type="Anticipated">December 2014</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Prevalence of anterior pituitary dysfunction</measure>
    <time_frame>at 3 (+/- 15 days) and 6 months (+/- 15 days)</time_frame>
    <description>Pituitary screening blood tests: cortisol, follicle stimulating hormone, luteinizing hormone, total testosterone (males) or estradiol (females), thyrotropin, free thyroxine, prolactin, insulin-like growth factor-1. Growth-hormone deficiency will be confirmed with a glucagon stimulation test. Adrenal Insufficiency will be confirmed with an Cosyntropin stimulation test.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prevalence of posterior pituitary dysfunction</measure>
    <time_frame>at 3 and 6 months</time_frame>
    <description>Pituitary Dysfunction: Screening Sodium. Diabetes Insipidus will be confirmed with a water deprivation test.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Background prevalence of hypopituitarism in a military population using the Department of Defense serum repository</measure>
    <time_frame>At completion of Enrollment</time_frame>
    <description>Screening labs for pituitary dysfunction repeated on frozen serum obtained prior to injury.</description>
  </other_outcome>
  <other_outcome>
    <measure>Relationship between hypopituitarism secondary to combat-related TBI and symptom scores using the Neurobehavioral Symptom Index.</measure>
    <time_frame>3 and 6 months post-injury</time_frame>
    <description>The Neurobehavioral Symptom Index is a validated measure of cognitive and somatic symptoms after Traumatic Brain Injury.</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Traumatic Brain Injury</condition>
  <condition>Hypopituitarism</condition>
  <arm_group>
    <arm_group_label>3 months post-injury</arm_group_label>
    <description>Male and female combat veterans age 18 years and older with the diagnosis of Traumatic Brain Injury caused by a blast that occurred 3 months prior to enrollment, 50% mild, 50% moderate and severe</description>
  </arm_group>
  <arm_group>
    <arm_group_label>6 months post-injury</arm_group_label>
    <description>Male and female combat veterans age 18 years and older with the diagnosis of Traumatic Brain Injury caused by a blast that occurred 6 months prior to enrollment, 50% mild, 50% moderate and severe</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blast Traumatic Brain Injury</intervention_name>
    <description>Exposure during combat to blast-wave mediated Traumatic Brain Injury</description>
    <arm_group_label>3 months post-injury</arm_group_label>
    <arm_group_label>6 months post-injury</arm_group_label>
    <other_name>bTBI</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      No specimens will be stored.&#xD;
&#xD;
      Blood Testing:&#xD;
&#xD;
      Testosterone 2ml Estradiol 2ml LH/FSH 3ml Prolactin 2ml IGF-1 1ml TSH 2ml Free T4 1ml Sodium&#xD;
      2ml Total blood for cosyntropin stim test 9ml Total blood for glucagon stim test 15ml Water&#xD;
      deprivation testing 12ml-32ml&#xD;
&#xD;
      Urine Testing:&#xD;
&#xD;
      HCG 2ml Water deprivation testing 8ml-18ml&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Male and female combat veterans age 18 years and older with the diagnosis of Traumatic&#xD;
        Brain Injury that occurred 3 and 6 months prior to enrollment.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Combat veterans who are 3 or 6 months post combat-related TBI and age 18yrs or older&#xD;
&#xD;
          -  Must demonstrate capacity for informed consent&#xD;
&#xD;
          -  Must be DEERS eligible (Military healthcare beneficiary)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy (to be assessed by urine HCG)&#xD;
&#xD;
          -  Use of hormonal contraceptives&#xD;
&#xD;
          -  Chronic oral or intravenous glucocorticoids&#xD;
&#xD;
          -  Use of hormonal therapy to include estrogen and testosterone&#xD;
&#xD;
          -  Prior diagnosis of hypopituitarism prior to combat related TBI&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew J. Brackbill, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>WalterReed National Military Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Andrew J Brackbill, M.D.</last_name>
    <phone>301-295-5183</phone>
    <email>tbiendocrine@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Walter Reed National Military Medical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20889</zip>
        <country>United States</country>
      </address>
    </facility>
    <investigator>
      <last_name>Andrew J Brackbill, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kate H Kinnaird, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Louis French, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Patrick W. Clyde, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Peter McIntyre, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>August 14, 2012</last_update_submitted>
  <last_update_submitted_qc>August 14, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 16, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Traumatic brain injury</keyword>
  <keyword>hypopituitarism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Hypopituitarism</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_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/NCT01666964
org study id: 350758-12
nct id: NCT01666964
lead sponsor: 
collaborator: 
has dmc: No
We would like to ascertain the prevalence of hypopituitarism after combat-related TBI. This
      will lead to enhanced awareness, recognition, and treatment of hypopituitarism, which can
      have life-saving ramifications and enhance quality of life and rehabilitation efforts in our
      combat veterans.
The prevalence of hypopituitarism after combat-related traumatic brain injury (TBI) is
      currently unknown. Recent civilian data on TBI show the prevalence of any pituitary hormone
      deficiency is as high as 80% after 12 months. While the military prevalence of
      hypopituitarism can be extrapolated from civilian data, a major limitation is the notably
      different mechanism of injury (i.e., blast) for military personnel compared to civilians
      (i.e., assaults, traffic accidents and falls). Little is known about the effect of shockwaves
      from a blast injury on central nervous system tissue, and due to the unique nature of
      blast-related TBI, the prevalence of pituitary dysfunction in affected service members may
      significantly differ from nonmilitary subjects in prior studies.
observational model: Case-Only
time perspective: Prospective
measure: Prevalence of anterior pituitary dysfunction
time frame: at 3 (+/- 15 days) and 6 months (+/- 15 days)
description: Pituitary screening blood tests: cortisol, follicle stimulating hormone, luteinizing hormone, total testosterone (males) or estradiol (females), thyrotropin, free thyroxine, prolactin, insulin-like growth factor-1. Growth-hormone deficiency will be confirmed with a glucagon stimulation test. Adrenal Insufficiency will be confirmed with an Cosyntropin stimulation test.
measure: Prevalence of posterior pituitary dysfunction
time frame: at 3 and 6 months
description: Pituitary Dysfunction: Screening Sodium. Diabetes Insipidus will be confirmed with a water deprivation test.
measure: Background prevalence of hypopituitarism in a military population using the Department of Defense serum repository
time frame: At completion of Enrollment
description: Screening labs for pituitary dysfunction repeated on frozen serum obtained prior to injury.
measure: Relationship between hypopituitarism secondary to combat-related TBI and symptom scores using the Neurobehavioral Symptom Index.
time frame: 3 and 6 months post-injury
description: The Neurobehavioral Symptom Index is a validated measure of cognitive and somatic symptoms after Traumatic Brain Injury.
arm group label: 3 months post-injury
description: Male and female combat veterans age 18 years and older with the diagnosis of Traumatic Brain Injury caused by a blast that occurred 3 months prior to enrollment, 50% mild, 50% moderate and severe
arm group label: 6 months post-injury
description: Male and female combat veterans age 18 years and older with the diagnosis of Traumatic Brain Injury caused by a blast that occurred 6 months prior to enrollment, 50% mild, 50% moderate and severe
intervention type: Other
intervention name: Blast Traumatic Brain Injury
description: Exposure during combat to blast-wave mediated Traumatic Brain Injury
arm group label: 3 months post-injury
arm group label: 6 months post-injury
other name: bTBI
No specimens will be stored.

      Blood Testing:

      Testosterone 2ml Estradiol 2ml LH/FSH 3ml Prolactin 2ml IGF-1 1ml TSH 2ml Free T4 1ml Sodium
      2ml Total blood for cosyntropin stim test 9ml Total blood for glucagon stim test 15ml Water
      deprivation testing 12ml-32ml

      Urine Testing:

      HCG 2ml Water deprivation testing 8ml-18ml
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrew J. Brackbill, M.D.
role: Principal Investigator
affiliation: WalterReed National Military Medical Center
last name: Andrew J Brackbill, M.D.
phone: 301-295-5183
email: tbiendocrine@gmail.com
facility: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Hypopituitarism
mesh term: Wounds and Injuries