<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/NCT04471740</url>
  </required_header>
  <id_info>
    <org_study_id>2020-07-02</org_study_id>
    <nct_id>NCT04471740</nct_id>
  </id_info>
  <brief_title>Normal Pressure Hydrocephalus and Sleep Apnea</brief_title>
  <acronym>NPH/OSA</acronym>
  <official_title>Normal-pressure Hydrocephalus. Relationship Between Sleep Apnea and Intracranial and Intraabdominal Pressures. Outcome Prognostic Factors in CSF Shunting. Features Guiding to Implant a Ventricle-peritoneal Versus a Ventriculo-atrial Shunt</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Valencia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Valencia</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>
      Normal-pressure hydrocephalus is associated with increases in the intracranial pressure&#xD;
      during the night sleep. Sleep apnea also increases the intracranial pressure during the&#xD;
      apneic spells. When patients are operated the distal part of the shunt is inserted inside the&#xD;
      abdominal cavity, which pressure also increases during the sleep apnea episodes. this is&#xD;
      particularly important considering that the recumbent position used to sleep further&#xD;
      increases the intraabdominal pressure and that impairs the CSF drainage through the shunt&#xD;
      system. The purpose of this study is to analyze the intracranial and intraabdominal pressures&#xD;
      during the sleep, particularly during the sleep apnea episodes to see which shunt should be&#xD;
      used, to which cavity should be drained (peritoneum or heart) and if correcting the sleep&#xD;
      apnea has some positive result on the hydrocephalus symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic hydrocephalus in adults, also known as normal pressure hydrocephalus or normal&#xD;
      pressure hydrocephalus, occurs with the classic Hakim-Adams triad, gait ataxia, or &quot;magnetic&#xD;
      gait&quot;, urinary incontinence and dementia.&#xD;
&#xD;
      Most of the cases have an idiopathic origin and are the only potentially reversible cause of&#xD;
      dementia with surgical treatment (by shunting the cerebrospinal fluid or CSF from the lateral&#xD;
      ventricles or the thecal sac to the peritoneal cavity or the right atrium), so it is&#xD;
      especially important to diagnose it and treat it properly.&#xD;
&#xD;
      Unfortunately, and despite all the diagnostic arsenal, the results of treatment using&#xD;
      cerebrospinal fluid shunts (lumbo-peritoneal or ventricle-peritoneal), even in the best&#xD;
      series, show 20-25% of poor results. These poor results have been attributed to many factors,&#xD;
      including associated cerebral vascular pathology problems, co-existing dementia symptoms not&#xD;
      always well diagnosed, Parkinson's disease, and, lastly, alterations in ventilatory rhythm.&#xD;
      during the night, specifically obstructive sleep apnea or OSA.&#xD;
&#xD;
      In reality, the name of normotensive hydrocephalus or hydrocephalus at normal pressure is&#xD;
      inaccurate because the intracranial pressure does rise and very markedly during sleep,&#xD;
      particularly during the REM phase of sleep. What is no longer so well known is because of&#xD;
      such significant increases in intracranial pressure occur. One possible explanation would be&#xD;
      that obstructive sleep apnea causes increased intracranial pressure. But it remains to be&#xD;
      clarified whether all patients with adult chronic hydrocephalus have sleep apnea, the&#xD;
      mechanism of action, and to what extent the treatment of hydrocephalus acts on sleep apnea&#xD;
      and vice versa.&#xD;
&#xD;
      Another aspect to consider is that the cerebrospinal fluid shunts work by the pressure&#xD;
      gradient between the intracranial cavity and the cavity into which the cephalo-spinal fluid&#xD;
      is drained66, usually the peritoneal fluid. During sleep apnea, there should be an increase&#xD;
      in intra-abdominal pressure, which would result in the ventricle-peritoneal and&#xD;
      lumbo-peritoneal shunts working suboptimally precisely at the time of day when they are most&#xD;
      needed, that is when intracranial pressure increases. But this correlation has never been&#xD;
      investigated or at least there are no publications about it.&#xD;
&#xD;
      Therefore, it is necessary to know the relationship between intracranial pressure, sleep&#xD;
      apnea, and intra-abdominal pressure at night. With these data, it will be possible to better&#xD;
      understand the dynamics of the circulation of the cerebrospinal fluid during the night (when&#xD;
      it is more pathological in chronic hydrocephalus in adults), what type of bypass valve is the&#xD;
      most indicated (whether or not it must have an anti-system siphon if it must be a&#xD;
      gravitational or flow valve) and in which patients the implantation of a ventricle-atrial&#xD;
      shunt may be an option to consider.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 2, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 2, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Patients diagnosed of normal-pressure hydrocephalus will undergo sleep studies to rule our sleep apnea. Those with sleep apnea will be treated for this condition and we will see if the hydrocephalus symptoms improve</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Patients will not be informed of the final treatment decided</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change of hydrocephalus symptoms with Mini-Mental State Examination</measure>
    <time_frame>1-2 months</time_frame>
    <description>Patients will be evaluated with the Mini_mental State Examination before and after CSF shunting to see the degree of improvement they get from this surgical treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of hydrocephalus symptoms with NPH scale after CSF shunt diversion</measure>
    <time_frame>1-2 months</time_frame>
    <description>Patients will be evaluated with the NPH before and after CSF shunting to see the degree of improvement they get from this surgical treatment</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Normal Pressure Hydrocephalus</condition>
  <condition>Sleep Apnea</condition>
  <condition>Cerebrospinal Fluid Shunt Occlusion</condition>
  <arm_group>
    <arm_group_label>Normal-pressure hydrocephalus only</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients suffering from normal-pressure hydrocephalus with NO sleep apnea</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal-pressure hydrocephalus with sleep apnea</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients suffering from normal-pressure hydrocephalus with sleep apnea</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>CSF shunt diversion</intervention_name>
    <description>Clinical response to a CSF shunt insertion</description>
    <arm_group_label>Normal-pressure hydrocephalus only</arm_group_label>
    <arm_group_label>Normal-pressure hydrocephalus with sleep apnea</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical condition compatible with normal-pressure hydrocephalus&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cerebral vascular disease&#xD;
&#xD;
          -  Dementia not due to normal-pressure hydrocephalus&#xD;
&#xD;
          -  Parkinson's disease&#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_contact>
    <last_name>Vicente Vanaclocha</last_name>
    <phone>34669790013</phone>
    <phone_ext>438500</phone_ext>
    <email>vvanaclo@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Vicente Vanaclocha</name>
      <address>
        <city>Valencia</city>
        <zip>46015</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vicente Vanaclocha Vanaclocha, Prof MD PhD</last_name>
      <phone>669790013</phone>
      <email>vvanaclo@hotmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Vicente Vanaclocha Vanaclocha</last_name>
      <phone>669790013</phone>
      <email>vvanaclo@hotmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <reference>
    <citation>Kawada T. Obstructive sleep apnea in patients with idiopathic normal-pressure hydrocephalus. J Neurol Sci. 2019 Feb 15;397:155. doi: 10.1016/j.jns.2019.01.006. Epub 2019 Jan 10. No abstract available.</citation>
    <PMID>30640151</PMID>
  </reference>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>November 2, 2022</last_update_submitted>
  <last_update_submitted_qc>November 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Normal pressure hydrocephalus</keyword>
  <keyword>Sleep apnea</keyword>
  <keyword>CSF shunt diversion</keyword>
  <keyword>Ventriculo-peritoneal shunt</keyword>
  <keyword>Ventriculo-atrial shunt</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apnea</mesh_term>
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <mesh_term>Hydrocephalus</mesh_term>
    <mesh_term>Hydrocephalus, Normal Pressure</mesh_term>
  </condition_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/NCT04471740
org study id: 2020-07-02
nct id: NCT04471740
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Normal-pressure hydrocephalus is associated with increases in the intracranial pressure
      during the night sleep. Sleep apnea also increases the intracranial pressure during the
      apneic spells. When patients are operated the distal part of the shunt is inserted inside the
      abdominal cavity, which pressure also increases during the sleep apnea episodes. this is
      particularly important considering that the recumbent position used to sleep further
      increases the intraabdominal pressure and that impairs the CSF drainage through the shunt
      system. The purpose of this study is to analyze the intracranial and intraabdominal pressures
      during the sleep, particularly during the sleep apnea episodes to see which shunt should be
      used, to which cavity should be drained (peritoneum or heart) and if correcting the sleep
      apnea has some positive result on the hydrocephalus symptoms.
Chronic hydrocephalus in adults, also known as normal pressure hydrocephalus or normal
      pressure hydrocephalus, occurs with the classic Hakim-Adams triad, gait ataxia, or "magnetic
      gait", urinary incontinence and dementia.

      Most of the cases have an idiopathic origin and are the only potentially reversible cause of
      dementia with surgical treatment (by shunting the cerebrospinal fluid or CSF from the lateral
      ventricles or the thecal sac to the peritoneal cavity or the right atrium), so it is
      especially important to diagnose it and treat it properly.

      Unfortunately, and despite all the diagnostic arsenal, the results of treatment using
      cerebrospinal fluid shunts (lumbo-peritoneal or ventricle-peritoneal), even in the best
      series, show 20-25% of poor results. These poor results have been attributed to many factors,
      including associated cerebral vascular pathology problems, co-existing dementia symptoms not
      always well diagnosed, Parkinson's disease, and, lastly, alterations in ventilatory rhythm.
      during the night, specifically obstructive sleep apnea or OSA.

      In reality, the name of normotensive hydrocephalus or hydrocephalus at normal pressure is
      inaccurate because the intracranial pressure does rise and very markedly during sleep,
      particularly during the REM phase of sleep. What is no longer so well known is because of
      such significant increases in intracranial pressure occur. One possible explanation would be
      that obstructive sleep apnea causes increased intracranial pressure. But it remains to be
      clarified whether all patients with adult chronic hydrocephalus have sleep apnea, the
      mechanism of action, and to what extent the treatment of hydrocephalus acts on sleep apnea
      and vice versa.

      Another aspect to consider is that the cerebrospinal fluid shunts work by the pressure
      gradient between the intracranial cavity and the cavity into which the cephalo-spinal fluid
      is drained66, usually the peritoneal fluid. During sleep apnea, there should be an increase
      in intra-abdominal pressure, which would result in the ventricle-peritoneal and
      lumbo-peritoneal shunts working suboptimally precisely at the time of day when they are most
      needed, that is when intracranial pressure increases. But this correlation has never been
      investigated or at least there are no publications about it.

      Therefore, it is necessary to know the relationship between intracranial pressure, sleep
      apnea, and intra-abdominal pressure at night. With these data, it will be possible to better
      understand the dynamics of the circulation of the cerebrospinal fluid during the night (when
      it is more pathological in chronic hydrocephalus in adults), what type of bypass valve is the
      most indicated (whether or not it must have an anti-system siphon if it must be a
      gravitational or flow valve) and in which patients the implantation of a ventricle-atrial
      shunt may be an option to consider.
allocation: Non-Randomized
intervention model: Single Group Assignment
intervention model description: Patients diagnosed of normal-pressure hydrocephalus will undergo sleep studies to rule our sleep apnea. Those with sleep apnea will be treated for this condition and we will see if the hydrocephalus symptoms improve
primary purpose: Treatment
masking: Single (Participant)
masking description: Patients will not be informed of the final treatment decided
measure: Change of hydrocephalus symptoms with Mini-Mental State Examination
time frame: 1-2 months
description: Patients will be evaluated with the Mini_mental State Examination before and after CSF shunting to see the degree of improvement they get from this surgical treatment
measure: Change of hydrocephalus symptoms with NPH scale after CSF shunt diversion
time frame: 1-2 months
description: Patients will be evaluated with the NPH before and after CSF shunting to see the degree of improvement they get from this surgical treatment
arm group label: Normal-pressure hydrocephalus only
arm group type: Experimental
description: Patients suffering from normal-pressure hydrocephalus with NO sleep apnea
arm group label: Normal-pressure hydrocephalus with sleep apnea
arm group type: Active Comparator
description: Patients suffering from normal-pressure hydrocephalus with sleep apnea
intervention type: Procedure
intervention name: CSF shunt diversion
description: Clinical response to a CSF shunt insertion
arm group label: Normal-pressure hydrocephalus only
arm group label: Normal-pressure hydrocephalus with sleep apnea
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Vicente Vanaclocha
phone: 34669790013
phone ext: 438500
email: vvanaclo@hotmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Spain
citation: Kawada T. Obstructive sleep apnea in patients with idiopathic normal-pressure hydrocephalus. J Neurol Sci. 2019 Feb 15;397:155. doi: 10.1016/j.jns.2019.01.006. Epub 2019 Jan 10. No abstract available.
PMID: 30640151
responsible party type: Sponsor
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Hydrocephalus
mesh term: Hydrocephalus, Normal Pressure
sharing ipd: No