xml: <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/NCT05966116</url>
    </required_header>
    <id_info>
      <org_study_id>UHDB/2023/055</org_study_id>
      <nct_id>NCT05966116</nct_id>
    </id_info>
    <brief_title>Sodium Accumulation Study in Haemodialysis: Brain Study</brief_title>
    <acronym>SASH-B</acronym>
    <official_title>Sodium Accumulation Study in Haemodialysis: Brain Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospitals of Derby and Burton NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University of Nottingham</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University Hospitals of Derby and Burton NHS Foundation Trust</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>
        The aim of the research study is to look at a new type of MRI scanning that can measure the&#xD;
        amount of sodium in different parts of the body. Sodium (or 'salt') levels are very important&#xD;
        in maintaining health, and high levels lead to high blood pressure. This is very important to&#xD;
        patients with kidney disease, as the kidney is the main organ that regulates the amount of&#xD;
        sodium in the body. It is possible to measure blood sodium levels, but this does not tell us&#xD;
        how much sodium is present in other areas of the body. Previously, it has not been possible&#xD;
        measure this. Sodium MRI (Na-MRI) is a new type of MRI scanning that can directly measure&#xD;
        sodium in other parts of body such as skin, muscles, kidneys, and brain. The investigators&#xD;
        believe that this will help to guide treatment in patients with kidney disease who are on&#xD;
        haemodialysis, research studies are needed to prove the benefits.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Haemodialysis (HD) sustains life in patients with end-stage kidney disease (ESKD) but is&#xD;
        associated with a marked increase in cognitive impairment, being three times more common and&#xD;
        presenting at a younger age. The predominant features of cognitive impairment associated with&#xD;
        HD are loss of executive function, including higher processing such as planning, task&#xD;
        prioritisation and self-regulation. The mechanism for development and acceleration of&#xD;
        cognitive impairment on dialysis is not well understood, however hypertension and&#xD;
        cardiovascular disease are likely to play a significant role, alongside changes in brain&#xD;
        perfusion as a result of dialysis itself, which has been shown in a prior study using PET-CT.&#xD;
  &#xD;
        Sodium balance is normally regulated by the kidneys in health, but has to be achieved by&#xD;
        sodium removal during HD for those with ESKD. Recent evidence suggests that accumulation of&#xD;
        sodium in tissue may be a critical factor impacting the development of hypertension and&#xD;
        cardiovascular disease (CVD) in patients with ESKD. Non-invasive methods are therefore&#xD;
        required to study tissue sodium accumulation in this context.&#xD;
  &#xD;
        23Na MRI has the potential to provide complementary quantitative parameters of tissue health,&#xD;
        in a non-invasive manner. Sodium homeostasis is central to maintenance of human physiology,&#xD;
        providing an index of cellular integrity and energy status. The maintenance of sodium&#xD;
        gradients across the cell membrane, by the Na+/K+ ATPase pump, enables 23Na MRI to&#xD;
        distinguish between different environments within organs, providing a biomarker of disease&#xD;
        status, notably kidney disease, hypertension, and brain disorders.&#xD;
  &#xD;
        Previously, traditional proton (1H) magnetic resonance imaging (MRI) in dialysis patients&#xD;
        demonstrated a decrease in grey matter T1 and an accompanying increase in white matter T1&#xD;
        when comparing scans before, during and after dialysis, In this context, T1 can be thought of&#xD;
        as a marker of water content. This demonstrates that changes in the brain occur as a direct&#xD;
        consequence of dialysis, with fluid and sodium shifts across cellular compartments the most&#xD;
        likely explanation. This is important, as it suggests a novel mechanism by which dialysis may&#xD;
        cause reductions in cognitive function. However, this needs further study to establish these&#xD;
        mechanisms with more confidence.&#xD;
  &#xD;
        At the SPMIC, a dual tuned proton(1H)/sodium(23Na) volume head RF coil for 23Na imaging of&#xD;
        the brain has been installed and interfaced; and imaging methods to perform 23Na MRI of the&#xD;
        brain have been optimised.&#xD;
  &#xD;
        This study proposes to utilise 23Na MRI of the brain along with proton measures of T1, before&#xD;
        and after dialysis within existing experimental set-up at SPMIC. This will provide new&#xD;
        insights into the direct effects of dialysis on brain sodium levels, and in turn deepen our&#xD;
        understanding of the link between sodium, fluid overload, dialysis and the brain.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2024</completion_date>
    <primary_completion_date type="Anticipated">August 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Proportion of brain images that can be analysed for sodium levels</measure>
      <time_frame>12 months</time_frame>
      <description>success criterion &gt; 85%</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in grey and white matter sodium levels</measure>
      <time_frame>12 months</time_frame>
      <description>comparing before and after dialysis</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Association between change in brain sodium levels to proton MRI measures</measure>
      <time_frame>12 months</time_frame>
      <description>grey/white matter volume, T1</description>
    </secondary_outcome>
    <enrollment type="Anticipated">10</enrollment>
    <condition>Dialysis; Complications</condition>
    <eligibility>
      <study_pop>
        <textblock>
          10 participants (5 male and 5 female) who are over 50 and under 75 years old who have been&#xD;
          on haemodialysis for more than 3 months&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age 50-75 years inclusive&#xD;
  &#xD;
            -  Male and female patients with CKD stage 5 receiving chronic haemodialysis&#xD;
  &#xD;
            -  Patient has been dialysis dependent for at least 3 months&#xD;
  &#xD;
            -  Must be able to follow simple instruction in English (on safety ground for MRI scans)&#xD;
               and be able to understand the nature and requirements of the study&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Active infection or malignancy&#xD;
  &#xD;
            -  Amputee&#xD;
  &#xD;
            -  Pregnancy&#xD;
  &#xD;
            -  Contraindication to MRI scanning including claustrophobia, pacemaker, metallic&#xD;
               implants etc&#xD;
  &#xD;
            -  Unable or unwilling to provide informed consent&#xD;
  &#xD;
            -  Medical conditions or overall physical frailty precludes scan session in opinion of&#xD;
               investigator&#xD;
  &#xD;
            -  Any condition which could interfere with the patient's ability to comply with the&#xD;
               study&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>50 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Rebecca A Noble, BMBS</last_name>
      <role>Principal Investigator</role>
      <affiliation>The University of Nottingham</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Rebecca A Noble, BMBS</last_name>
      <phone>01332340131</phone>
      <phone_ext>88262</phone_ext>
      <email>rebecca.noble1@nottingham.ac.uk</email>
    </overall_contact>
    <location>
      <facility>
        <name>Centre for Kidney Research and Innovation</name>
        <address>
          <city>Derby</city>
          <zip>DE22 3NE</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
      <contact>
        <last_name>Rebecca A Noble, BMBS</last_name>
        <email>rebecca.noble1@nottingham.ac.uk</email>
      </contact>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 21, 2023</study_first_submitted>
    <study_first_submitted_qc>July 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05966116
  org study id: UHDB/2023/055
  nct id: NCT05966116
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The aim of the research study is to look at a new type of MRI scanning that can measure the
        amount of sodium in different parts of the body. Sodium (or 'salt') levels are very important
        in maintaining health, and high levels lead to high blood pressure. This is very important to
        patients with kidney disease, as the kidney is the main organ that regulates the amount of
        sodium in the body. It is possible to measure blood sodium levels, but this does not tell us
        how much sodium is present in other areas of the body. Previously, it has not been possible
        measure this. Sodium MRI (Na-MRI) is a new type of MRI scanning that can directly measure
        sodium in other parts of body such as skin, muscles, kidneys, and brain. The investigators
        believe that this will help to guide treatment in patients with kidney disease who are on
        haemodialysis, research studies are needed to prove the benefits.
  Haemodialysis (HD) sustains life in patients with end-stage kidney disease (ESKD) but is
        associated with a marked increase in cognitive impairment, being three times more common and
        presenting at a younger age. The predominant features of cognitive impairment associated with
        HD are loss of executive function, including higher processing such as planning, task
        prioritisation and self-regulation. The mechanism for development and acceleration of
        cognitive impairment on dialysis is not well understood, however hypertension and
        cardiovascular disease are likely to play a significant role, alongside changes in brain
        perfusion as a result of dialysis itself, which has been shown in a prior study using PET-CT.
  
        Sodium balance is normally regulated by the kidneys in health, but has to be achieved by
        sodium removal during HD for those with ESKD. Recent evidence suggests that accumulation of
        sodium in tissue may be a critical factor impacting the development of hypertension and
        cardiovascular disease (CVD) in patients with ESKD. Non-invasive methods are therefore
        required to study tissue sodium accumulation in this context.
  
        23Na MRI has the potential to provide complementary quantitative parameters of tissue health,
        in a non-invasive manner. Sodium homeostasis is central to maintenance of human physiology,
        providing an index of cellular integrity and energy status. The maintenance of sodium
        gradients across the cell membrane, by the Na+/K+ ATPase pump, enables 23Na MRI to
        distinguish between different environments within organs, providing a biomarker of disease
        status, notably kidney disease, hypertension, and brain disorders.
  
        Previously, traditional proton (1H) magnetic resonance imaging (MRI) in dialysis patients
        demonstrated a decrease in grey matter T1 and an accompanying increase in white matter T1
        when comparing scans before, during and after dialysis, In this context, T1 can be thought of
        as a marker of water content. This demonstrates that changes in the brain occur as a direct
        consequence of dialysis, with fluid and sodium shifts across cellular compartments the most
        likely explanation. This is important, as it suggests a novel mechanism by which dialysis may
        cause reductions in cognitive function. However, this needs further study to establish these
        mechanisms with more confidence.
  
        At the SPMIC, a dual tuned proton(1H)/sodium(23Na) volume head RF coil for 23Na imaging of
        the brain has been installed and interfaced; and imaging methods to perform 23Na MRI of the
        brain have been optimised.
  
        This study proposes to utilise 23Na MRI of the brain along with proton measures of T1, before
        and after dialysis within existing experimental set-up at SPMIC. This will provide new
        insights into the direct effects of dialysis on brain sodium levels, and in turn deepen our
        understanding of the link between sodium, fluid overload, dialysis and the brain.
  observational model: Cohort
  time perspective: Prospective
  measure: Proportion of brain images that can be analysed for sodium levels
  time frame: 12 months
  description: success criterion > 85%
  measure: Change in grey and white matter sodium levels
  time frame: 12 months
  description: comparing before and after dialysis
  measure: Association between change in brain sodium levels to proton MRI measures
  time frame: 12 months
  description: grey/white matter volume, T1
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 50 Years
  maximum age: 75 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Rebecca A Noble, BMBS
  role: Principal Investigator
  affiliation: The University of Nottingham
  last name: Rebecca A Noble, BMBS
  phone: 01332340131
  phone ext: 88262
  email: rebecca.noble1@nottingham.ac.uk
  facility: 
  contact: 
  country: United Kingdom
  responsible party type: Sponsor