<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/NCT04482764</url>
  </required_header>
  <id_info>
    <org_study_id>BHS-VPA-SH-2017</org_study_id>
    <nct_id>NCT04482764</nct_id>
  </id_info>
  <brief_title>Valproic Acid in Treating Cyanotic Breath Holding Spells</brief_title>
  <official_title>The Effectiveness of Valproic Acid in Treating Frequent Cyanotic Breath Holding Spells</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</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>
      Breath holding spells (BHS) are common non-epileptic paroxysmal behavioral involuntary&#xD;
      episodes occurring in up to 5.9% of healthy children. The attacks occur in early childhood&#xD;
      (0.5-3 years) but are self-limited by school age (4-5 years old) (90%). Classically, BHS were&#xD;
      classified as cyanotic (blue), pallid (pale) and mixed based on the color change of the child&#xD;
      during the spell. In general, cyanotic spells have been classically described in a toddler&#xD;
      with excessive temper tantrums [stubborn, easily frustration or annoyed. The mechanisms of&#xD;
      BHS are controversial. The most suggested cause of BHS is instability of the autonomic&#xD;
      nervous system, inhibition of respiratory effort and cyanosis in cyanotic BHS and bradycardia&#xD;
      or a brief asystole and cerebral hypoperfusion in pallid BHS. Iron deficiency anemia (IDA)&#xD;
      has been widely regarded as a risk factor for BHS in nearly 50% of children due to reduced&#xD;
      brain oxygenation [4]. It is generally agreed that the long-term prognosis is considered good&#xD;
      [1]. There is no definite therapy for BHS. In children with low frequency spells, parental&#xD;
      reassurance are just enough; however, high frequency spells may result in anxiety to the&#xD;
      parents or fear from sudden death of the child or development of mental subnormality.&#xD;
      Treatment of iron has been reported to result in reduction of the frequency of spells or its&#xD;
      stoppage. Some reported improvement of BHS with piracetam [a nootropic drug known to increase&#xD;
      brain oxygenation]. We did not find systematized published reports evaluating the&#xD;
      effectiveness of antiepileptic drugs (AEDs) in reduction of spells frequency of cyanotic BHS&#xD;
      or their stoppage.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 30, 2017</start_date>
  <completion_date type="Actual">December 30, 2018</completion_date>
  <primary_completion_date type="Actual">January 30, 2018</primary_completion_date>
  <phase>Phase 1</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>frequency of spells after starting treatment with valproic acid</measure>
    <time_frame>6 months</time_frame>
    <description>The parents or legal guardians are the sources of information about the frequency of spells.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Breathhold</condition>
  <arm_group>
    <arm_group_label>cyanotic breath holding spells</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>drug, valproic acid: 5mg/kg/d for 6 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Valproic Acid</intervention_name>
    <description>Treatment of children with frequent cyanotic breath holding spells (at least 4 spells per week) with 5 mg/kg/day for 6 months.</description>
    <arm_group_label>cyanotic breath holding spells</arm_group_label>
    <other_name>sodium valproate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria :&#xD;
&#xD;
          1. Children with high frequency spells (≥ 4/week) of CBHS.&#xD;
&#xD;
          2. Children with parents who were wishing to provide treatment to their children.&#xD;
&#xD;
          3. Failure of alternatives modalities of treatment (e.g. iron supplements, piracetam,&#xD;
             non-specific vitamins, etc) (tried for ≥ 3 months) to reduce the frequency of spells&#xD;
             or stop them.&#xD;
&#xD;
          4. Follow-up for 6 months after starting treatment with valproic acid.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Primary neurologic disease, history of epilepsy or febrile convulsions, abnormal&#xD;
             neurological examination and abnormal EEG.&#xD;
&#xD;
          2. Primary cardiac disease or presence of long QT syndrome in the ECG.&#xD;
&#xD;
          3. Presence of a hematologic (other than IDA) or other medical disease, electrolyte&#xD;
             disturbance, hypoglycemia, hypocalcemia, impaired kidney or liver function tests.&#xD;
&#xD;
          4. Those with a doubtful diagnosis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>5 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sherifa A Hamed, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assiut University, Faculty of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Assiut University Hospitals, Faculty of Medicine</name>
      <address>
        <city>Assiut</city>
        <zip>71516</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>October 3, 2017</study_first_submitted>
  <study_first_submitted_qc>July 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>July 18, 2020</last_update_submitted>
  <last_update_submitted_qc>July 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Sherifa Ahmed Hamed</investigator_full_name>
    <investigator_title>Professor of Neurology</investigator_title>
  </responsible_party>
  <keyword>Breath holding spells</keyword>
  <keyword>cyanosis</keyword>
  <keyword>valproic acid</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Valproic Acid</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/NCT04482764
org study id: BHS-VPA-SH-2017
nct id: NCT04482764
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Breath holding spells (BHS) are common non-epileptic paroxysmal behavioral involuntary
      episodes occurring in up to 5.9% of healthy children. The attacks occur in early childhood
      (0.5-3 years) but are self-limited by school age (4-5 years old) (90%). Classically, BHS were
      classified as cyanotic (blue), pallid (pale) and mixed based on the color change of the child
      during the spell. In general, cyanotic spells have been classically described in a toddler
      with excessive temper tantrums [stubborn, easily frustration or annoyed. The mechanisms of
      BHS are controversial. The most suggested cause of BHS is instability of the autonomic
      nervous system, inhibition of respiratory effort and cyanosis in cyanotic BHS and bradycardia
      or a brief asystole and cerebral hypoperfusion in pallid BHS. Iron deficiency anemia (IDA)
      has been widely regarded as a risk factor for BHS in nearly 50% of children due to reduced
      brain oxygenation [4]. It is generally agreed that the long-term prognosis is considered good
      [1]. There is no definite therapy for BHS. In children with low frequency spells, parental
      reassurance are just enough; however, high frequency spells may result in anxiety to the
      parents or fear from sudden death of the child or development of mental subnormality.
      Treatment of iron has been reported to result in reduction of the frequency of spells or its
      stoppage. Some reported improvement of BHS with piracetam [a nootropic drug known to increase
      brain oxygenation]. We did not find systematized published reports evaluating the
      effectiveness of antiepileptic drugs (AEDs) in reduction of spells frequency of cyanotic BHS
      or their stoppage.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: frequency of spells after starting treatment with valproic acid
time frame: 6 months
description: The parents or legal guardians are the sources of information about the frequency of spells.
arm group label: cyanotic breath holding spells
arm group type: Other
description: drug, valproic acid: 5mg/kg/d for 6 months
intervention type: Drug
intervention name: Valproic Acid
description: Treatment of children with frequent cyanotic breath holding spells (at least 4 spells per week) with 5 mg/kg/day for 6 months.
arm group label: cyanotic breath holding spells
other name: sodium valproate
criteria: 
gender: All
minimum age: 6 Months
maximum age: 5 Years
healthy volunteers: No
last name: Sherifa A Hamed, M.D.
role: Principal Investigator
affiliation: Assiut University, Faculty of Medicine
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Sherifa Ahmed Hamed
investigator title: Professor of Neurology
mesh term: Valproic Acid
sharing ipd: No