<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/NCT03032328</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00036629</org_study_id>
    <nct_id>NCT03032328</nct_id>
  </id_info>
  <brief_title>Vitamin D Deficiency and Dysautonomia</brief_title>
  <official_title>Comprehensive Assessment of Vascular and Autonomic Function in Children With Low Vitamin D</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In previous work the investigator identified a group of children between the ages of 10-18&#xD;
      years whose diagnostic workup for chronic nausea unexplained by conventional diagnostic tests&#xD;
      has unexpectedly revealed underlying cardiovascular instability manifesting as orthostatic&#xD;
      intolerance, primary defined as postural orthostatic tachycardia syndrome (POTS) (88%). While&#xD;
      this is an atypical initial presentation for orthostatic intolerance in general, the&#xD;
      investigator believes that the cardiovascular problem is serious and represents a cause of&#xD;
      the nausea in a majority of these individuals, as treatment of the POTS with fludrocortisone&#xD;
      reduced the symptoms of nausea. While fludrocortisone treatment abrogates the fall in&#xD;
      baroreflex sensitivity (BRS) during tilt in part, it did not completely correct the&#xD;
      tachycardia symptoms or the BRS suppression during HUT. Furthermore it caused an elevation in&#xD;
      MAP in supine position, which may lead to future cardiovascular problems such as early onset&#xD;
      hypertension and cardiac hypertrophy. This argues for a different treatment approach. The&#xD;
      investigator presents preliminary data in this application revealing that OI subjects tend to&#xD;
      have lower 25-hydroxy vitamin D (25(OH)D) compared to non OI subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators approach will combine HUT testing coupled with autonomic testing that&#xD;
      includes continuous blood pressure and HR measurements, Baroreflex Sensitivity and Hear Rate&#xD;
      Variability, to establish objective autonomic profiles, along with vascular testing including&#xD;
      Pulse Wave Velocity, Ankle Brachial Index at rest and measures of blood volume of different&#xD;
      compartments, Systemic Vascular Resistance and cardiac output at rest and in response to&#xD;
      hand-grip stress. This will allow the treating physician to provide patients with a specific&#xD;
      diagnosis, and ultimately develop data for more focused, rational treatments than currently&#xD;
      achieved. The full vascular profile is also novel and has the potential to improve&#xD;
      therapeutic management of the participants independent of the outcomes with the vitamin D&#xD;
      supplementation. This study is designed to recruit 80 participants into 4 groups of 20 each.&#xD;
      The 4 groups represent non OI (those recruited from the clinics for nausea but without a&#xD;
      positive tilt test) or those showing orthostatic intolerance (POTS alone, OH, and syncope).&#xD;
      The general objective of this proposal is to address this gap in knowledge by determining&#xD;
      vascular function, the neurohumoral profile and autonomic status supine and in response to&#xD;
      HUT in OI subjects with low vitamin D levels in comparison with subjects who test negative&#xD;
      for OI on the HUT.&#xD;
&#xD;
      The investigators aim to examine the effect of vitamin D replacement on these measures,&#xD;
      providing the possibility of therapeutic use of vitamin D to treat or ameliorate the symptoms&#xD;
      associated with OI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2016</start_date>
  <completion_date type="Actual">December 21, 2022</completion_date>
  <primary_completion_date type="Actual">December 21, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Improvement of orthostatic intolerance symptoms usint tilt table test</measure>
    <time_frame>2 months</time_frame>
    <description>assessment of orthostatic intolerance will be done using tilt table test</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>improvement of nausea symptoms</measure>
    <time_frame>2 months</time_frame>
    <description>assessment of nausea symptoms will be done using nausea questionaire</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Vitamin D Deficiency</condition>
  <condition>Orthostatic Intolerance</condition>
  <condition>Nausea</condition>
  <arm_group>
    <arm_group_label>vitamin D supplement</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patient's will be given a vitamin D</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>vitamin D supplement</intervention_name>
    <description>Patients will be given a dose of vitamin D for at least 2 months</description>
    <arm_group_label>vitamin D supplement</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The age range of 10-18 years was chosen as we anticipate these patients will be&#xD;
             capable of adequately answering nausea symptom questionnaires and cooperating during&#xD;
             autonomic and tilt table testing&#xD;
&#xD;
          -  Patients will be recruited from the pediatric GI clinic if they meet Rome III criteria&#xD;
             for childhood functional dyspepsia with nausea as the predominant symptom which&#xD;
             includes: persistent or recurrent pain or discomfort (including nausea) in the upper&#xD;
             abdomen not relieved with defecation and not associated an inflammatory, anatomic,&#xD;
             metabolic, or neoplastic process&#xD;
&#xD;
          -  Patients will be recruited from the pediatric cardiology clinic for presenting&#xD;
             symptoms of unexplained syncope not associated with cardiac anatomic anomalies or&#xD;
             other identified cardiac pathology&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients will be excluded if a metabolic, mechanical, or mucosal inflammatory cause&#xD;
             has been defined to explain their gastrointestinal symptoms. This would include, for&#xD;
             example, a diagnosis of inflammatory bowel disease, celiac disease, liver or&#xD;
             pancreatic disease, hiatal hernia, or bowel obstruction&#xD;
&#xD;
          -  Patients with significant cardiac or cardiovascular disease, malignancy, or other&#xD;
             comorbid conditions precluding successful completion of a 45 minute tilt test will be&#xD;
             excluded.&#xD;
&#xD;
          -  Subjects who are incapable or unwilling to discontinue medications affecting autonomic&#xD;
             function will be excluded.&#xD;
&#xD;
          -  Patients with diabetes will be excluded due to the possibility that the autonomic&#xD;
             dysfunction results from a peripheral neuropathy. (We have successfully recruited&#xD;
             these numbers of subjects in less than 2 years in a previous study of similar design&#xD;
&#xD;
          -  Patients who are pregnant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hossam Shaltout, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Wake Forest Baptist Health</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>January 25, 2023</last_update_submitted>
  <last_update_submitted_qc>January 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Orthostatic Intolerance</mesh_term>
    <mesh_term>Vitamin D Deficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 14, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03032328/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03032328
org study id: IRB00036629
nct id: NCT03032328
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In previous work the investigator identified a group of children between the ages of 10-18
      years whose diagnostic workup for chronic nausea unexplained by conventional diagnostic tests
      has unexpectedly revealed underlying cardiovascular instability manifesting as orthostatic
      intolerance, primary defined as postural orthostatic tachycardia syndrome (POTS) (88%). While
      this is an atypical initial presentation for orthostatic intolerance in general, the
      investigator believes that the cardiovascular problem is serious and represents a cause of
      the nausea in a majority of these individuals, as treatment of the POTS with fludrocortisone
      reduced the symptoms of nausea. While fludrocortisone treatment abrogates the fall in
      baroreflex sensitivity (BRS) during tilt in part, it did not completely correct the
      tachycardia symptoms or the BRS suppression during HUT. Furthermore it caused an elevation in
      MAP in supine position, which may lead to future cardiovascular problems such as early onset
      hypertension and cardiac hypertrophy. This argues for a different treatment approach. The
      investigator presents preliminary data in this application revealing that OI subjects tend to
      have lower 25-hydroxy vitamin D (25(OH)D) compared to non OI subjects.
The investigators approach will combine HUT testing coupled with autonomic testing that
      includes continuous blood pressure and HR measurements, Baroreflex Sensitivity and Hear Rate
      Variability, to establish objective autonomic profiles, along with vascular testing including
      Pulse Wave Velocity, Ankle Brachial Index at rest and measures of blood volume of different
      compartments, Systemic Vascular Resistance and cardiac output at rest and in response to
      hand-grip stress. This will allow the treating physician to provide patients with a specific
      diagnosis, and ultimately develop data for more focused, rational treatments than currently
      achieved. The full vascular profile is also novel and has the potential to improve
      therapeutic management of the participants independent of the outcomes with the vitamin D
      supplementation. This study is designed to recruit 80 participants into 4 groups of 20 each.
      The 4 groups represent non OI (those recruited from the clinics for nausea but without a
      positive tilt test) or those showing orthostatic intolerance (POTS alone, OH, and syncope).
      The general objective of this proposal is to address this gap in knowledge by determining
      vascular function, the neurohumoral profile and autonomic status supine and in response to
      HUT in OI subjects with low vitamin D levels in comparison with subjects who test negative
      for OI on the HUT.

      The investigators aim to examine the effect of vitamin D replacement on these measures,
      providing the possibility of therapeutic use of vitamin D to treat or ameliorate the symptoms
      associated with OI.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Improvement of orthostatic intolerance symptoms usint tilt table test
time frame: 2 months
description: assessment of orthostatic intolerance will be done using tilt table test
measure: improvement of nausea symptoms
time frame: 2 months
description: assessment of nausea symptoms will be done using nausea questionaire
arm group label: vitamin D supplement
arm group type: Experimental
description: patient's will be given a vitamin D
intervention type: Dietary Supplement
intervention name: vitamin D supplement
description: Patients will be given a dose of vitamin D for at least 2 months
arm group label: vitamin D supplement
criteria: 
gender: All
minimum age: 10 Years
maximum age: 18 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Hossam Shaltout, PhD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
facility: 
country: United States
responsible party type: Sponsor
mesh term: Orthostatic Intolerance
mesh term: Vitamin D Deficiency
mesh term: Vitamin D
sharing ipd: No
provided document: 