<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/NCT04449666</url>
  </required_header>
  <id_info>
    <org_study_id>SAB-VOL</org_study_id>
    <nct_id>NCT04449666</nct_id>
  </id_info>
  <brief_title>Hippocampal Volume and Memory Functions in Aneurysmal Subarachnoid Hemorrhage</brief_title>
  <official_title>Investigation of the Relationship Between Hippocampal Volume and Memory Functions in in Patients With Aneurysmal Subarachnoid Hemorrhage (aSAH)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BDH-Klinik Hessisch Oldendorf</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BDH-Klinik Hessisch Oldendorf</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>
      Neuropsychological and functional long-term consequences of subarachnoid hemorrhages (SAH)&#xD;
      represent a great challenge, since sometimes considerable cognitive deficits occur without&#xD;
      evidence of substantial brain damage. In this study, we want to examine if the frequently&#xD;
      observed memory deficits are associated with hippocampal atrophy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Long-term or even permanent neuropsychological impairments are frequently observed after&#xD;
      aneurysmal subarachnoid hemorrhages (aSAH). Among the most common impairments after aSAH are&#xD;
      memory deficits. Volumetric MRI studies suggest an association of memory dysfunctions with&#xD;
      temporal atrophy, especially of the hippocampus. In a previous study, 77 patients with good&#xD;
      or moderate clinical outcome after aSAH were examined one year after discharge (Bendel et&#xD;
      al., 2006). Temporomesial atrophy was detected without direct brain damage, e.g. by secondary&#xD;
      ischemia. Due to the effects of complex cognitive impairments on the quality of life and&#xD;
      participation in social and professional life, this relationship will be examined in more&#xD;
      detail in the planned study. Specifically, we will investigate to what extent the frequently&#xD;
      observed discrepancy between severe memory impairment and normal structural imaging results&#xD;
      (no focal lesions in temporomesial areas) is due to hippocampal atrophy. In contrast to&#xD;
      Bender and colleagues, this question will be investigated in the acute phase of the disease,&#xD;
      immediately after admission to inpatient neurological rehabilitation.&#xD;
&#xD;
      Over a period of 24 months, 29 neurological rehabilitation patients with aSAH (Hunt &amp; Hess&#xD;
      grade I and II) are going to be included. Within the first week (day 1 to 7) after study&#xD;
      enrollment, a native MRI examination (without contrast agent) is performed, in which a&#xD;
      high-resolution 3D-MPRAGE sequence (T1 weighting) is measured in the sagittal plane. After&#xD;
      checking the data quality of the 3D-MPRAGE sequence, especially with regard to its&#xD;
      suitability for hippocampal volume determination, a comprehensive neuropsychological&#xD;
      examination is performed, in which specific memory and attentional functions are tested.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Anticipated">December 15, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 15, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Changed hippocampal volume in aSAB</measure>
    <time_frame>2 weeks</time_frame>
    <description>Hypothesis: patients have smaller hippocampal volume than healthy control subjects. For the hippocampal volume a structural MRI scan (3D-MPRAGE) is obtained</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changed memory function in aSAB</measure>
    <time_frame>2 weeks</time_frame>
    <description>Hypothesis: patients have lower scores in the Visual and Verbal memory test (VVM) than healthy control subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Influence of the type of therapy on the hippocampal volume</measure>
    <time_frame>2 weeks</time_frame>
    <description>Hypothesis: hippocampal volumes differ between aSAH patients with surgical or endovascular treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Influence of the lesion site on the hippocampal volume</measure>
    <time_frame>2 weeks</time_frame>
    <description>Hypothesis: there are no differences between ispi- and contralateral hippocampal volumes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interrater reliability</measure>
    <time_frame>2 weeks</time_frame>
    <description>Hypothesis: It is expected that there will be no difference in the ratings of hippocampal volume between two independent raters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changed intracranial volume in aSAB</measure>
    <time_frame>2 weeks</time_frame>
    <description>Hypothesis: patients have smaller intracranial volume than healthy control subjects.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Neurologic Disorder</condition>
  <condition>Subarachnoid Hemorrhage, Aneurysmal</condition>
  <arm_group>
    <arm_group_label>Experimental group</arm_group_label>
    <description>Patients undergoing neurological rehabilitation after aneurysmal subarachnoid hemorrhage</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <description>Healthy adults controlled for age, gender and educational status</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Neuropsychological assessment and structural MRI</intervention_name>
    <description>Complex neuropsychological assessment testing attentional and memory functions. Additionally, a structural MRI is measured.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Experimental group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        neurological rehabilitation patients with aneurysmal subarachnoid hemorrhage (Hunt &amp; Hess&#xD;
        grade I or II)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  neurological rehabilitation patients in phase B - D&#xD;
&#xD;
          -  at minimum eight weeks after disease onset&#xD;
&#xD;
          -  aneurysmal subarachnoid hemorrhage (Hunt &amp; Hess grade I or II)&#xD;
&#xD;
          -  written consent from the patient's legal representative&#xD;
&#xD;
          -  exclusion of pregnancy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  insufficient cardiorespiratory stability&#xD;
&#xD;
          -  previous brain damage&#xD;
&#xD;
          -  mental disorders (dementia, depression)&#xD;
&#xD;
          -  colonization with multi-resistant pathogens&#xD;
&#xD;
          -  MRI contraindications&#xD;
&#xD;
          -  claustrophobia&#xD;
&#xD;
          -  weight &gt; 120 kg&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Jens D Rollnik, MD</last_name>
    <role>Study Director</role>
    <affiliation>BDH-Clinic Hessisch Oldendorf</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Melanie Boltzmann, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>BDH-Clinic Hessisch Oldendorf</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Melanie Boltzmann, PhD</last_name>
    <phone>0049 5152 781 256</phone>
    <email>m.boltzmann@bdh-klinik-hessisch.oldendorf</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Simone B Schmidt, PhD</last_name>
    <phone>0049 5152 781 215</phone>
    <email>si.schmidt@bdh-klinik-hessisch.oldendorf</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>BDH-Clinic Hessisch Oldendorf</name>
      <address>
        <city>Hessisch Oldendorf</city>
        <zip>31840</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Melanie Boltzmann, PhD</last_name>
      <phone>0049 5152 781 256</phone>
      <email>m.boltzmann@bdh-klinik-hessisch-oldendorf.de</email>
    </contact>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Bendel P, Koivisto T, Hanninen T, Kolehmainen A, Kononen M, Hurskainen H, Pennanen C, Vanninen R. Subarachnoid hemorrhage is followed by temporomesial volume loss: MRI volumetric study. Neurology. 2006 Aug 22;67(4):575-82. doi: 10.1212/01.wnl.0000230221.95670.bf.</citation>
    <PMID>16924007</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 29, 2020</study_first_posted>
  <last_update_submitted>August 1, 2023</last_update_submitted>
  <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neurological rehabilitation</keyword>
  <keyword>Hippocampal volume</keyword>
  <keyword>Memory deficits</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Subarachnoid Hemorrhage</mesh_term>
    <mesh_term>Nervous System Diseases</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All IPD that underlie results in a publication.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Period of availability begins when results are published, at the earliest in Dec 2022</ipd_time_frame>
    <ipd_access_criteria>IPD can be obtained from the principal investigator upon reasonable request.</ipd_access_criteria>
  </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/NCT04449666
org study id: SAB-VOL
nct id: NCT04449666
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Neuropsychological and functional long-term consequences of subarachnoid hemorrhages (SAH)
      represent a great challenge, since sometimes considerable cognitive deficits occur without
      evidence of substantial brain damage. In this study, we want to examine if the frequently
      observed memory deficits are associated with hippocampal atrophy.
Long-term or even permanent neuropsychological impairments are frequently observed after
      aneurysmal subarachnoid hemorrhages (aSAH). Among the most common impairments after aSAH are
      memory deficits. Volumetric MRI studies suggest an association of memory dysfunctions with
      temporal atrophy, especially of the hippocampus. In a previous study, 77 patients with good
      or moderate clinical outcome after aSAH were examined one year after discharge (Bendel et
      al., 2006). Temporomesial atrophy was detected without direct brain damage, e.g. by secondary
      ischemia. Due to the effects of complex cognitive impairments on the quality of life and
      participation in social and professional life, this relationship will be examined in more
      detail in the planned study. Specifically, we will investigate to what extent the frequently
      observed discrepancy between severe memory impairment and normal structural imaging results
      (no focal lesions in temporomesial areas) is due to hippocampal atrophy. In contrast to
      Bender and colleagues, this question will be investigated in the acute phase of the disease,
      immediately after admission to inpatient neurological rehabilitation.

      Over a period of 24 months, 29 neurological rehabilitation patients with aSAH (Hunt & Hess
      grade I and II) are going to be included. Within the first week (day 1 to 7) after study
      enrollment, a native MRI examination (without contrast agent) is performed, in which a
      high-resolution 3D-MPRAGE sequence (T1 weighting) is measured in the sagittal plane. After
      checking the data quality of the 3D-MPRAGE sequence, especially with regard to its
      suitability for hippocampal volume determination, a comprehensive neuropsychological
      examination is performed, in which specific memory and attentional functions are tested.
observational model: Case-Control
time perspective: Prospective
measure: Changed hippocampal volume in aSAB
time frame: 2 weeks
description: Hypothesis: patients have smaller hippocampal volume than healthy control subjects. For the hippocampal volume a structural MRI scan (3D-MPRAGE) is obtained
measure: Changed memory function in aSAB
time frame: 2 weeks
description: Hypothesis: patients have lower scores in the Visual and Verbal memory test (VVM) than healthy control subjects.
measure: Influence of the type of therapy on the hippocampal volume
time frame: 2 weeks
description: Hypothesis: hippocampal volumes differ between aSAH patients with surgical or endovascular treatment.
measure: Influence of the lesion site on the hippocampal volume
time frame: 2 weeks
description: Hypothesis: there are no differences between ispi- and contralateral hippocampal volumes
measure: Interrater reliability
time frame: 2 weeks
description: Hypothesis: It is expected that there will be no difference in the ratings of hippocampal volume between two independent raters.
measure: Changed intracranial volume in aSAB
time frame: 2 weeks
description: Hypothesis: patients have smaller intracranial volume than healthy control subjects.
arm group label: Experimental group
description: Patients undergoing neurological rehabilitation after aneurysmal subarachnoid hemorrhage
arm group label: Control group
description: Healthy adults controlled for age, gender and educational status
intervention type: Diagnostic Test
intervention name: Neuropsychological assessment and structural MRI
description: Complex neuropsychological assessment testing attentional and memory functions. Additionally, a structural MRI is measured.
arm group label: Control group
arm group label: Experimental group
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
last name: Jens D Rollnik, MD
role: Study Director
affiliation: BDH-Clinic Hessisch Oldendorf
last name: Melanie Boltzmann, PhD
role: Principal Investigator
affiliation: BDH-Clinic Hessisch Oldendorf
last name: Melanie Boltzmann, PhD
phone: 0049 5152 781 256
email: m.boltzmann@bdh-klinik-hessisch.oldendorf
last name: Simone B Schmidt, PhD
phone: 0049 5152 781 215
email: si.schmidt@bdh-klinik-hessisch.oldendorf
facility: 
status: Recruiting
contact: 
country: Germany
citation: Bendel P, Koivisto T, Hanninen T, Kolehmainen A, Kononen M, Hurskainen H, Pennanen C, Vanninen R. Subarachnoid hemorrhage is followed by temporomesial volume loss: MRI volumetric study. Neurology. 2006 Aug 22;67(4):575-82. doi: 10.1212/01.wnl.0000230221.95670.bf.
PMID: 16924007
responsible party type: Sponsor
mesh term: Subarachnoid Hemorrhage
mesh term: Nervous System Diseases
mesh term: Hemorrhage
sharing ipd: Yes
ipd description: All IPD that underlie results in a publication.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Period of availability begins when results are published, at the earliest in Dec 2022
ipd access criteria: IPD can be obtained from the principal investigator upon reasonable request.