<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/NCT03267602</url>
  </required_header>
  <id_info>
    <org_study_id>201208075RIC</org_study_id>
    <nct_id>NCT03267602</nct_id>
  </id_info>
  <brief_title>Role of Sleep Apnea in the Neuropsychological Function in Down Syndrome People</brief_title>
  <official_title>Role of Sleep Apnea in the Neuropsychological Function in Down Syndrome People</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</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>
      This is the first study about Neuropsychological function and OSAS in Taiwan. Although the&#xD;
      correlation between OSAS and neuropsychological abnormalities had been reported, it is worth&#xD;
      to understand more about the detailed domains that involved in our cohort. After this,&#xD;
      investigators can dissect the cause of mental retardation in DS and help for further&#xD;
      treatment strategies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Down Syndrome (DS) is the most common cause of mental retardation with incidence of 1 in 848&#xD;
      (Lin, Hu et al. 1991). Although prenatal Down syndrome and Amniocentesis had been applied for&#xD;
      years, in the survey of 2005, current birth incidence of DS is 1.6 in 10,000 live birth,&#xD;
      meaning a 30-50 new cases per year (Jou, Kuo et al. 2005). Patients with DS will have&#xD;
      multisystemic manifestations including short stature, mental retardation, dysmorphism,&#xD;
      congenital heart disease, congenital anomaly of gastrointestinal and genitourinary tract,&#xD;
      abnormal endocrine function, leukemia and leukemoid reaction. Beside mental retardation,&#xD;
      other anomalies could be treated or controlled by current medical care. The IQ of DS is&#xD;
      around 20-80 with significant cognitive, language, and behavior problems (Dierssen,&#xD;
      Ortiz-Abalia et al. 2006).&#xD;
&#xD;
      In addition, obstructive sleep apnea syndrome (OSAS) had been observed in DS people with&#xD;
      prevalence about 45-79% in the literature (de Miguel-Diez, Villa-Asensi et al. 2003; Dyken,&#xD;
      Lin-Dyken et al. 2003; Shott, Amin et al. 2006; Fitzgerald, Paul et al. 2007), which is much&#xD;
      higher than the 1-3% prevalence rate in general population (Holmes 1993; Gislason and&#xD;
      Benediktsdottir 1995). The reasons of DS people prone to have OSAS are due to the combination&#xD;
      of anatomical and physiological factors. In DS people, facial dysmorphism (midfacial&#xD;
      hypoplasia, mandibular hypoplasia), macroglossia, small hypopharynx, pharyngeal hypotonia,&#xD;
      tonsil and adenoid enlargement, obesity, laryngomalacia, and tracheomalacia contributed to&#xD;
      upper airway obstructions in DS people (Trois, Capone et al. 2009; Pandit and Fitzgerald&#xD;
      2012). In addition, DS people has increased incidence of lower respiratory tract diseases&#xD;
      including gastroesophageal reflux, immunological dysfunction, tracheal bronchus, airway&#xD;
      malacia, congenital heart disease, and pulmonary hypoplasia, which will predispose to OSAS.&#xD;
      While growing up, DS people still have generalized hypotonia with increasing risk of&#xD;
      developing hypothyroidism and obesity, which are also risk factors for OSAS (Trois, Capone et&#xD;
      al. 2009).&#xD;
&#xD;
      It has been noted that sleep disordered breathing is associated with neurocognitive deficit,&#xD;
      particularly of memory, learning, attention, hyperactivity, executive functioning, cognitive&#xD;
      capacity, and poor school performance (Beebe 2006; Pandit and Fitzgerald 2012). And a number&#xD;
      of studies have reported improved attention, executive functioning, analytical thinking,&#xD;
      verbal functioning, memory and academic progress at 6-12 months post- adenotonsillectomy&#xD;
      (Chervin, Ruzicka et al. 2006). In DS, study demonstrated that a higher number of apneic&#xD;
      episodes on polysomnography was correlated to the decreased visuoperceptual skill in DS&#xD;
      (Andreou, Galanopoulou et al. 2002). Similarly, presence of snoring in DS was associated with&#xD;
      a much higher rate of disruptive school behavior than without snore (Carskadon, Pueschel et&#xD;
      al. 1993). Although learning disability and memory defect had been globally known in DS, the&#xD;
      behavior, cognitive, and developmental impairment caused by OSAS is especially concerning&#xD;
      because it might adversely affect their ability, even the social adaptation (Rihtman,&#xD;
      Tekuzener et al. 2010) . Therefore, investigators would like to know the correlation between&#xD;
      severity of OSAS and Neurocognitive and behavior in DS people in Taiwan. Also, investigators&#xD;
      would like to follow the Neurocognitive and behavior changes in those who had been treated&#xD;
      for OSAS, including tonsillectomy or Bilevel Positive Airway Pressure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2012</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</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>Assessed the sleep apnea level with Apnoea-Hypopnoea Index (AHI) score.</measure>
    <time_frame>3 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessed neuropsychological functions with Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R) vocabulary subdomain score.</measure>
    <time_frame>3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessed the memory domain that subtest of Sentence (WPPSI-R) .</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessed the memory domain that forward memory (Leiter International Performance Scale-Revised) .</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of participants's Visuospatial functions with Geometric Design (WPPSI-R).</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of participants's Visuospatial functions with Block Design (WPPSI-R).</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Executive domain was assessed with TOWER (Developmental NEuroPSYchological Assessment, NEPSY)</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessed the Language domain with Vocabulary subtest</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessed the Sensorimotor domain with Visuomotor Precision-train and car</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement the effectiveness of therapy before and after treatment with Apnoea-Hypopnoea Index (AHI).</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement the effectiveness of therapy before and after treatment with Oxygen Desaturation Index (ODI).</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Down Syndrome</condition>
  <arm_group>
    <arm_group_label>Continuous Positive Airway Pressure (CPAP) Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>CPAP</intervention_name>
    <description>If following patients are suffering from sleep apnea and agree to receive treatment,&#xD;
older than 18 years, AHI&gt; 15 and present obvious symptoms or&#xD;
less than 18 years, AHI still&gt; 5 after tonsillectomy and present obvious symptoms.&#xD;
Investigators will process CPAP treatment for 3 months, and do neuropsychological assessment and sleep examination after treatment for 6 months.</description>
    <arm_group_label>Continuous Positive Airway Pressure (CPAP) Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosed with Down's syndrome by chromosome test, over 6 years old and IQ&gt; 40.&#xD;
&#xD;
          2. Participants and caregiver who are willing and comply with study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known to have uncontrolled heart, stomach, kidney or neurological / psychiatric&#xD;
             disorders.&#xD;
&#xD;
          2. Cannot comply with study。&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ni-Chung Lee, M.D, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>August 31, 2017</last_update_submitted>
  <last_update_submitted_qc>August 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2017</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>Down Syndrome</mesh_term>
    <mesh_term>Syndrome</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/NCT03267602
org study id: 201208075RIC
nct id: NCT03267602
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is the first study about Neuropsychological function and OSAS in Taiwan. Although the
      correlation between OSAS and neuropsychological abnormalities had been reported, it is worth
      to understand more about the detailed domains that involved in our cohort. After this,
      investigators can dissect the cause of mental retardation in DS and help for further
      treatment strategies.
Down Syndrome (DS) is the most common cause of mental retardation with incidence of 1 in 848
      (Lin, Hu et al. 1991). Although prenatal Down syndrome and Amniocentesis had been applied for
      years, in the survey of 2005, current birth incidence of DS is 1.6 in 10,000 live birth,
      meaning a 30-50 new cases per year (Jou, Kuo et al. 2005). Patients with DS will have
      multisystemic manifestations including short stature, mental retardation, dysmorphism,
      congenital heart disease, congenital anomaly of gastrointestinal and genitourinary tract,
      abnormal endocrine function, leukemia and leukemoid reaction. Beside mental retardation,
      other anomalies could be treated or controlled by current medical care. The IQ of DS is
      around 20-80 with significant cognitive, language, and behavior problems (Dierssen,
      Ortiz-Abalia et al. 2006).

      In addition, obstructive sleep apnea syndrome (OSAS) had been observed in DS people with
      prevalence about 45-79% in the literature (de Miguel-Diez, Villa-Asensi et al. 2003; Dyken,
      Lin-Dyken et al. 2003; Shott, Amin et al. 2006; Fitzgerald, Paul et al. 2007), which is much
      higher than the 1-3% prevalence rate in general population (Holmes 1993; Gislason and
      Benediktsdottir 1995). The reasons of DS people prone to have OSAS are due to the combination
      of anatomical and physiological factors. In DS people, facial dysmorphism (midfacial
      hypoplasia, mandibular hypoplasia), macroglossia, small hypopharynx, pharyngeal hypotonia,
      tonsil and adenoid enlargement, obesity, laryngomalacia, and tracheomalacia contributed to
      upper airway obstructions in DS people (Trois, Capone et al. 2009; Pandit and Fitzgerald
      2012). In addition, DS people has increased incidence of lower respiratory tract diseases
      including gastroesophageal reflux, immunological dysfunction, tracheal bronchus, airway
      malacia, congenital heart disease, and pulmonary hypoplasia, which will predispose to OSAS.
      While growing up, DS people still have generalized hypotonia with increasing risk of
      developing hypothyroidism and obesity, which are also risk factors for OSAS (Trois, Capone et
      al. 2009).

      It has been noted that sleep disordered breathing is associated with neurocognitive deficit,
      particularly of memory, learning, attention, hyperactivity, executive functioning, cognitive
      capacity, and poor school performance (Beebe 2006; Pandit and Fitzgerald 2012). And a number
      of studies have reported improved attention, executive functioning, analytical thinking,
      verbal functioning, memory and academic progress at 6-12 months post- adenotonsillectomy
      (Chervin, Ruzicka et al. 2006). In DS, study demonstrated that a higher number of apneic
      episodes on polysomnography was correlated to the decreased visuoperceptual skill in DS
      (Andreou, Galanopoulou et al. 2002). Similarly, presence of snoring in DS was associated with
      a much higher rate of disruptive school behavior than without snore (Carskadon, Pueschel et
      al. 1993). Although learning disability and memory defect had been globally known in DS, the
      behavior, cognitive, and developmental impairment caused by OSAS is especially concerning
      because it might adversely affect their ability, even the social adaptation (Rihtman,
      Tekuzener et al. 2010) . Therefore, investigators would like to know the correlation between
      severity of OSAS and Neurocognitive and behavior in DS people in Taiwan. Also, investigators
      would like to follow the Neurocognitive and behavior changes in those who had been treated
      for OSAS, including tonsillectomy or Bilevel Positive Airway Pressure.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Assessed the sleep apnea level with Apnoea-Hypopnoea Index (AHI) score.
time frame: 3 months
measure: Assessed neuropsychological functions with Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R) vocabulary subdomain score.
time frame: 3 months
measure: Assessed the memory domain that subtest of Sentence (WPPSI-R) .
time frame: 3 months
measure: Assessed the memory domain that forward memory (Leiter International Performance Scale-Revised) .
time frame: 3 months
measure: Evaluation of participants's Visuospatial functions with Geometric Design (WPPSI-R).
time frame: 3 months
measure: Evaluation of participants's Visuospatial functions with Block Design (WPPSI-R).
time frame: 3 months
measure: The Executive domain was assessed with TOWER (Developmental NEuroPSYchological Assessment, NEPSY)
time frame: 3 months
measure: Assessed the Language domain with Vocabulary subtest
time frame: 3 months
measure: Assessed the Sensorimotor domain with Visuomotor Precision-train and car
time frame: 3 months
measure: Measurement the effectiveness of therapy before and after treatment with Apnoea-Hypopnoea Index (AHI).
time frame: 12 months
measure: Measurement the effectiveness of therapy before and after treatment with Oxygen Desaturation Index (ODI).
time frame: 12 months
arm group label: Continuous Positive Airway Pressure (CPAP) Therapy
arm group type: Experimental
intervention type: Device
intervention name: CPAP
description: If following patients are suffering from sleep apnea and agree to receive treatment,
older than 18 years, AHI> 15 and present obvious symptoms or
less than 18 years, AHI still> 5 after tonsillectomy and present obvious symptoms.
Investigators will process CPAP treatment for 3 months, and do neuropsychological assessment and sleep examination after treatment for 6 months.
arm group label: Continuous Positive Airway Pressure (CPAP) Therapy
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Ni-Chung Lee, M.D, Ph.D
role: Principal Investigator
affiliation: National Taiwan University Hospital
responsible party type: Sponsor
mesh term: Down Syndrome
mesh term: Syndrome