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/NCT06019182</url>
    </required_header>
    <id_info>
      <org_study_id>10001681</org_study_id>
      <secondary_id>001681-CH</secondary_id>
      <nct_id>NCT06019182</nct_id>
    </id_info>
    <brief_title>MEHMO Natural History and Biomarkers</brief_title>
    <official_title>Investigations of Individuals With MEHMO Syndrome or eIF2-Pathway Related Conditions</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
        <agency_class>NIH</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>National Institutes of Health Clinical Center (CC)</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This observational natural history study will follow individuals with MEHMO (Mental&#xD;
        disability, Epileptic seizure, Hypopituitarism/Hypogenitalism, Microcephaly, Obesity)&#xD;
        syndrome or an eIF2-pathway related disorder, who have symptoms such as intellectual delay,&#xD;
        seizures, abnormal hormone and blood sugar levels, and decreased motor skills.&#xD;
  &#xD;
        No current treatment for these conditions is available. A major impediment to the testing of&#xD;
        potential therapeutic interventions is the lack of well-defined outcome measures. This&#xD;
        protocol seeks to identify biochemical and clinical markers to monitor disease progression,&#xD;
        and better understand the natural history of these conditions.&#xD;
  &#xD;
        Any person diagnosed with MEHMO syndrome or related conditions, who can travel to the NIH&#xD;
        Clinical Center can participate in this study.&#xD;
  &#xD;
        The study involves:&#xD;
  &#xD;
          -  General health assessment and evaluation&#xD;
  &#xD;
          -  Imaging studies&#xD;
  &#xD;
          -  Laboratory tests&#xD;
  &#xD;
          -  Collection of blood, urine, spinal fluid, skin biopsy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Study Description: This is a prospective natural history study of individuals who have MEHMO&#xD;
        syndrome or eIF2-pathway related conditions, or who are carriers of EIF2S3-related conditions&#xD;
        to generate hypotheses for further understanding of disease pathophysiology, diagnosis,&#xD;
        prognosis, management, and treatment. The protocol aims to enroll and follow affected or&#xD;
        carrier individuals longitudinally to establish a repository of concurrent evaluations and&#xD;
        biomaterials, as well as to enroll unaffected individuals for collection of informative&#xD;
        comparable data and samples.&#xD;
  &#xD;
        Objectives:&#xD;
  &#xD;
        Primary Objective:&#xD;
  &#xD;
        Characterize the presentation of MEHMO syndrome and eIF2 pathway related conditions.&#xD;
  &#xD;
        Secondary Objectives:&#xD;
  &#xD;
          1. Identify disease-reflective fluid biomarkers&#xD;
  &#xD;
          2. Develop a disease severity rating scale or classification algorithm&#xD;
  &#xD;
          3. Assess tolerability and feasibility of study evaluations&#xD;
  &#xD;
          4. Establish a repository of participant data and samples for future research&#xD;
  &#xD;
        Endpoints:&#xD;
  &#xD;
        Primary Endpoint:&#xD;
  &#xD;
        Frequency and time-to-event of signs and symptoms.&#xD;
  &#xD;
        Secondary Endpoints:&#xD;
  &#xD;
          1. Mean difference of candidate fluid biomarkers level in affected versus carrier versus&#xD;
             unaffected individuals&#xD;
  &#xD;
          2. Correlation of rating scale or classification algorithm to age, genotype, or other&#xD;
             variables&#xD;
  &#xD;
          3. Frequency of completed evaluations and reasons for Noncompletion&#xD;
  &#xD;
        Study Population: 25 affected individuals 1-week of age or older 25 EIF2S3-variant carrier&#xD;
        individuals 1-month of age or older 50 unaffected individuals 1 month of age or older of any&#xD;
        sex, race, ethnicity, geographic location who can participate without increased risk to&#xD;
        personal health.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 21, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2053</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2053</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>Other</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Characterize the presentation of MEHMO syndrome and eIF2-pathway related conditions.</measure>
      <time_frame>Ongoing</time_frame>
      <description>Frequency and time-to-event of signs and symptoms. These will allow systematic and potentially quantitative measures of disease presentation that can then be operationalized to develop disease rating scale(s) and correlative measures for candidate biomarkers.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Identify disease-reflective fluid biomarkers</measure>
      <time_frame>Ongoing</time_frame>
      <description>Difference and range of candidate fluid biomarkers level in affected vs. carrier vs. unaffected individuals. Sensitive or specific quantitative markers will allow for improved diagnosis, management, and treatment of MEHMO syndrome or eIF2-pathway related disorders.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Develop a disease severity rating scale or classification algorithm.</measure>
      <time_frame>Ongoing</time_frame>
      <description>A quantitative rating scale or classification algorithm that reflects other disease aspects will provide a standardized tool for communication amongst all involved in the clinical care and research of MEHMO syndrome or eIF2-pathway related disorders.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assess tolerability and feasibility of study evaluations.</measure>
      <time_frame>Ongoing</time_frame>
      <description>Frequency of completed evaluations and reasons for non-completion will inform design of future trials for MEHMO syndrome or eIF2-pathway related disorders.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Characterize EIF2S3-carrier phenotype.</measure>
      <time_frame>Ongoing</time_frame>
      <description>Frequency and time-to-event of signs and symptoms at disease-relevant intervals will provide a systematic evaluation of EIF2S3- carrier phenotype.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Establish a repository of participant data and samples for future research.</measure>
      <time_frame>Ongoing</time_frame>
      <description>A repository of concurrently collected participant data and samples for future research will provide resources for future research towards understanding the disease and developing interventions.</description>
    </secondary_outcome>
    <number_of_groups>3</number_of_groups>
    <enrollment type="Anticipated">150</enrollment>
    <condition>Intellectual Disability</condition>
    <condition>Epilepsy</condition>
    <condition>Hypogonadisms</condition>
    <condition>Microcephaly</condition>
    <condition>Nervous System Malformations</condition>
    <condition>Obesity</condition>
    <arm_group>
      <arm_group_label>Affected</arm_group_label>
      <description>Individuals who have MEHMO syndrome or eIF2-pathway related conditions 1-week of age or older.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Carrier</arm_group_label>
      <description>EIF2S3-variant carrier individuals 1-month of age or older.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Unaffected Non-carrier</arm_group_label>
      <description>Unaffected individuals 1 month of age or older who are 1st degree relative of an affected individual</description>
    </arm_group>
    <eligibility>
      <study_pop>
        <textblock>
          Inclusion Criteria: An individual must be &gt; 1-week of age if affected, or &gt; 1-month of age&#xD;
          if unaffected. For Screening: Have a combination of signs/symptoms suggestive of MEHMO&#xD;
          syndrome, AND no or inconclusive molecular testing. For Main Study: 1. Have a combination&#xD;
          of signs/symptoms suggestive of MEHMO syndrome, AND disease-associated variant(s) or&#xD;
          variant(s) of uncertain significance in one of the eIF2-pathway related genes OR 2. Be a&#xD;
          first-degree relative of an individual with EIF2S3-related MEHMO syndrome, AND a carrier of&#xD;
          the pathogenic or likely pathogenic variant. OR 3. Be a non-affected, non-carrier family&#xD;
          member of an individual with MEHMO syndrome or an eIF2-pathway related condition. Exclusion&#xD;
          Criteria: Any individual who, in the opinion of the Investigators, is unable to comply with&#xD;
          the protocol or have medical conditions that would potentially increase the risk of&#xD;
          participation.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          -  Inclusion Criteria&#xD;
  &#xD;
          To be eligible to participate in this study, an individual must meet the following&#xD;
          criteria:&#xD;
  &#xD;
          Be greater than or equal to 1-week of age if affected, or greater than or equal to 1-month&#xD;
          of age if unaffected.&#xD;
  &#xD;
          19&#xD;
  &#xD;
          For Screening:&#xD;
  &#xD;
          Have a combination of signs/symptoms suggestive of MEHMO syndrome, AND no or inconclusive&#xD;
          molecular testing.&#xD;
  &#xD;
          For Main Study&#xD;
  &#xD;
            1. Have a combination of signs/symptoms suggestive of MEHMO syndrome, AND&#xD;
               disease-associated variant(s) or variant(s) of uncertain significance in one of the&#xD;
               eIF2-&#xD;
  &#xD;
               pathway related genes&#xD;
  &#xD;
               OR&#xD;
  &#xD;
            2. Be a first-degree relative of an individual with EIF2S3-related MEHMO syndrome, AND a&#xD;
               carrier of the pathogenic or likely pathogenic variant.&#xD;
  &#xD;
               OR&#xD;
  &#xD;
            3. Be a non-affected, non-carrier family member of an individual with MEHMO syndrome or&#xD;
               an eIF2-pathway related condition.&#xD;
  &#xD;
          Exclusion Criteria&#xD;
  &#xD;
          Any individual who, in the opinion of the Investigators, is unable to comply with the&#xD;
          protocol&#xD;
  &#xD;
          or have medical conditions that would potentially increase the risk of participation will&#xD;
          be&#xD;
  &#xD;
          excluded from participation in this study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>1 Week</minimum_age>
      <maximum_age>100 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>An N Dang Do, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>An N Dang Do, M.D.</last_name>
      <phone>(301) 496-8849</phone>
      <email>an.dangdo@nih.gov</email>
    </overall_contact>
    <location>
      <facility>
        <name>National Institutes of Health Clinical Center</name>
        <address>
          <city>Bethesda</city>
          <state>Maryland</state>
          <zip>20892</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>An Dang Do, M.D.</last_name>
        <phone>301-496-8849</phone>
        <email>an.dangdo@nih.gov</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_001681-CH.html</url>
      <description>NIH Clinical Center Detailed Web Page</description>
    </link>
    <verification_date>August 28, 2023</verification_date>
    <study_first_submitted>August 30, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 31, 2023</study_first_posted>
    <last_update_submitted>September 15, 2023</last_update_submitted>
    <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>MEHMO</keyword>
    <keyword>X-linked MEHMO Syndrome</keyword>
    <keyword>eIF2-Pathway Related Conditions</keyword>
    <keyword>EIF2S3</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Microcephaly</mesh_term>
      <mesh_term>Intellectual Disability</mesh_term>
      <mesh_term>Nervous System Malformations</mesh_term>
      <mesh_term>Hypogonadism</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>.Requests for sharing of relevant IPD for clinical management purpose or directly from the individual participant will be considered on case basis and are not guaranteed to result in sharing of IPD.</ipd_description>
    </patient_data>
    <!-- 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/NCT06019182
  org study id: 10001681
  secondary id: 001681-CH
  nct id: NCT06019182
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This observational natural history study will follow individuals with MEHMO (Mental
        disability, Epileptic seizure, Hypopituitarism/Hypogenitalism, Microcephaly, Obesity)
        syndrome or an eIF2-pathway related disorder, who have symptoms such as intellectual delay,
        seizures, abnormal hormone and blood sugar levels, and decreased motor skills.
  
        No current treatment for these conditions is available. A major impediment to the testing of
        potential therapeutic interventions is the lack of well-defined outcome measures. This
        protocol seeks to identify biochemical and clinical markers to monitor disease progression,
        and better understand the natural history of these conditions.
  
        Any person diagnosed with MEHMO syndrome or related conditions, who can travel to the NIH
        Clinical Center can participate in this study.
  
        The study involves:
  
          -  General health assessment and evaluation
  
          -  Imaging studies
  
          -  Laboratory tests
  
          -  Collection of blood, urine, spinal fluid, skin biopsy.
  Study Description: This is a prospective natural history study of individuals who have MEHMO
        syndrome or eIF2-pathway related conditions, or who are carriers of EIF2S3-related conditions
        to generate hypotheses for further understanding of disease pathophysiology, diagnosis,
        prognosis, management, and treatment. The protocol aims to enroll and follow affected or
        carrier individuals longitudinally to establish a repository of concurrent evaluations and
        biomaterials, as well as to enroll unaffected individuals for collection of informative
        comparable data and samples.
  
        Objectives:
  
        Primary Objective:
  
        Characterize the presentation of MEHMO syndrome and eIF2 pathway related conditions.
  
        Secondary Objectives:
  
          1. Identify disease-reflective fluid biomarkers
  
          2. Develop a disease severity rating scale or classification algorithm
  
          3. Assess tolerability and feasibility of study evaluations
  
          4. Establish a repository of participant data and samples for future research
  
        Endpoints:
  
        Primary Endpoint:
  
        Frequency and time-to-event of signs and symptoms.
  
        Secondary Endpoints:
  
          1. Mean difference of candidate fluid biomarkers level in affected versus carrier versus
             unaffected individuals
  
          2. Correlation of rating scale or classification algorithm to age, genotype, or other
             variables
  
          3. Frequency of completed evaluations and reasons for Noncompletion
  
        Study Population: 25 affected individuals 1-week of age or older 25 EIF2S3-variant carrier
        individuals 1-month of age or older 50 unaffected individuals 1 month of age or older of any
        sex, race, ethnicity, geographic location who can participate without increased risk to
        personal health.
  observational model: Cohort
  time perspective: Other
  measure: Characterize the presentation of MEHMO syndrome and eIF2-pathway related conditions.
  time frame: Ongoing
  description: Frequency and time-to-event of signs and symptoms. These will allow systematic and potentially quantitative measures of disease presentation that can then be operationalized to develop disease rating scale(s) and correlative measures for candidate biomarkers.
  measure: Identify disease-reflective fluid biomarkers
  time frame: Ongoing
  description: Difference and range of candidate fluid biomarkers level in affected vs. carrier vs. unaffected individuals. Sensitive or specific quantitative markers will allow for improved diagnosis, management, and treatment of MEHMO syndrome or eIF2-pathway related disorders.
  measure: Develop a disease severity rating scale or classification algorithm.
  time frame: Ongoing
  description: A quantitative rating scale or classification algorithm that reflects other disease aspects will provide a standardized tool for communication amongst all involved in the clinical care and research of MEHMO syndrome or eIF2-pathway related disorders.
  measure: Assess tolerability and feasibility of study evaluations.
  time frame: Ongoing
  description: Frequency of completed evaluations and reasons for non-completion will inform design of future trials for MEHMO syndrome or eIF2-pathway related disorders.
  measure: Characterize EIF2S3-carrier phenotype.
  time frame: Ongoing
  description: Frequency and time-to-event of signs and symptoms at disease-relevant intervals will provide a systematic evaluation of EIF2S3- carrier phenotype.
  measure: Establish a repository of participant data and samples for future research.
  time frame: Ongoing
  description: A repository of concurrently collected participant data and samples for future research will provide resources for future research towards understanding the disease and developing interventions.
  arm group label: Affected
  description: Individuals who have MEHMO syndrome or eIF2-pathway related conditions 1-week of age or older.
  arm group label: Carrier
  description: EIF2S3-variant carrier individuals 1-month of age or older.
  arm group label: Unaffected Non-carrier
  description: Unaffected individuals 1 month of age or older who are 1st degree relative of an affected individual
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 1 Week
  maximum age: 100 Years
  healthy volunteers: No
  last name: An N Dang Do, M.D.
  role: Principal Investigator
  affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  last name: An N Dang Do, M.D.
  phone: (301) 496-8849
  email: an.dangdo@nih.gov
  facility: 
  contact: 
  country: United States
  url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_001681-CH.html
  description: NIH Clinical Center Detailed Web Page
  responsible party type: Sponsor
  mesh term: Microcephaly
  mesh term: Intellectual Disability
  mesh term: Nervous System Malformations
  mesh term: Hypogonadism
  sharing ipd: Undecided
  ipd description: .Requests for sharing of relevant IPD for clinical management purpose or directly from the individual participant will be considered on case basis and are not guaranteed to result in sharing of IPD.