<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/NCT04419870</url>
  </required_header>
  <id_info>
    <org_study_id>200120</org_study_id>
    <secondary_id>20-HG-0120</secondary_id>
    <nct_id>NCT04419870</nct_id>
  </id_info>
  <brief_title>Acute Infection in Mitochondrial Disease: Metabolism, Infection and Immunity During the COVID19 Pandemic</brief_title>
  <official_title>Acute Infection in Mitochondrial Disease: An Observational Prospective Natural History Study of Metabolism, Infection and Immunity During the COVID19 Pandemic</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Human Genome Research Institute (NHGRI)</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>
      Background:&#xD;
&#xD;
      Mitochondrial disease is a rare disorder. It can cause poor growth, developmental delays,&#xD;
      muscle weakness, and other symptoms. The disease is usually inherited. It can be present at&#xD;
      birth or develop later in life. Infection is a major cause of disease and death in people&#xD;
      with this disease. Researchers want to learn more about how infection and the declining&#xD;
      health of people who have this disease may be related to the COVID-19 pandemic. To do this,&#xD;
      researchers will study the DNA of people who become ill with suspected or confirmed&#xD;
      coronavirus. Their DNA will be compared to the DNA of their family members.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To learn more about how genes may play a role in how COVID-19 affects people with&#xD;
      mitochondrial disease.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      People age 2 months and older with mitochondrial disease and a suspected or confirmed&#xD;
      diagnosis of COVID-19.&lt;TAB&gt;&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will complete a questionnaire about their health history. Their medical records&#xD;
      may be reviewed. They will give a blood sample.&#xD;
&#xD;
      If the participant becomes ill, they may have a videoconference with a doctor or nurse at the&#xD;
      NIH to perform a physical exam. They may be contacted after their illness to give updates on&#xD;
      their health. They may be asked to give extra blood samples or complete extra questionnaires.&#xD;
&#xD;
      Participants genetic data will be put into a database. The data will be labeled with a code&#xD;
      and not their name. The data will be shared with other researchers.&#xD;
&#xD;
      Participation lasts about 1 year. This may be extended if the participant is very ill.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Infection is a major cause of morbidity and mortality individuals with mitochondrial disease,&#xD;
      frequently triggering metabolic decompensation, multiorgan dysfunction, and neurologic&#xD;
      deterioration. In the context of the recent COVID19 pandemic, people with mitochondrial&#xD;
      disease are at increased risk for severe disease and poor outcomes if infected. However, the&#xD;
      mechanisms for this link between infection and clinical decline are incompletely understood.&#xD;
      Given that people with mitochondrial disease are particularly susceptible to infection and&#xD;
      may experience delayed recovery, we hypothesize that this is in part due to immune factors&#xD;
      that influence host-pathogen interactions. The purpose of this protocol is to collect&#xD;
      biological specimens to identify immune signatures that contribute to the phenotype of&#xD;
      infection and outcomes in patients with mitochondrial disease who become ill during the&#xD;
      COVID19 pandemic. In order to compare these cases with others of similar genetic backgrounds&#xD;
      and environmental exposures, we will also collect specimens from family members. We will then&#xD;
      examine how these signatures correlate with comprehensive quantifiable clinical measures&#xD;
      throughout the course of disease, from presenting symptoms, through acute decompensation,&#xD;
      stabilization and convalescence. While this protocol is developed during the COVID-19&#xD;
      pandemic with a focus on a specific infectious pathogen, we hope that this study will extend&#xD;
      beyond the pandemic in an effort to more broadly understand acute infectious illness in&#xD;
      patients with mitochondrial disease. Additionally, it will serve as a remote adjunct to the&#xD;
      NIH MINI Study, a natural history study focused on the immunophenotype of mitochondrial&#xD;
      disease that is conducted at the NIH Clinical Center.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 21, 2020</start_date>
  <completion_date type="Anticipated">May 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2025</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>We will perform whole blood transcriptomic analysis, humoral response profiling and soluble mediator profiling.</measure>
    <time_frame>Undefined for natural history study</time_frame>
    <description>To identify immune signatures that associate with host responses to disease that would allow improved patient stratification and identification of potential therapeutic targets to mitigate the severe symptoms and sequelae of infection in mitochondrial disease.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patient Medical Records for Data Abstraction</measure>
    <time_frame>Undefined for natural history study</time_frame>
    <description>to stratify severity of illness based on clinical factors (e.g. intensive care status, ventilatory support, clinical laboratory data, radiology records)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient centered outcomes data via questionnaires</measure>
    <time_frame>Undefined for natural history study</time_frame>
    <description>to understand functional status, healthcare resource access and other sociodynamic factors as they affect the mitochondrial disease community.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Mitochondrial Disease</condition>
  <arm_group>
    <arm_group_label>Group 1a</arm_group_label>
    <description>Patients with mitochondrial disease who are ill with suspected or confirmed COVID19</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1b</arm_group_label>
    <description>Patients with mitochondrial disease who are NOT ill with acute infection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <description>Family members of patients with mitochondrial disease in Group 1</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Three study populations will be recruited. (Group 1a) Participants with mitochondrial&#xD;
        disease in any location who are two months of age or older and become acutely ill during&#xD;
        the COVID19 pandemic; (Group 1b) Participants with mitochondrial disease in any location&#xD;
        who are two months of age or older and are not acutely ill (Group 2) Family members of&#xD;
        group 1 to serve as controls. We anticipate approximately 50 participants in group 1 and up&#xD;
        to 150 participants in Group 2.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
        In order to be eligible to participate in this study, an individual must meet all of the&#xD;
        following criteria:&#xD;
&#xD;
        Group 1a&#xD;
&#xD;
          1. Participants must be two months of age or older.&#xD;
&#xD;
          2. Participants must have a diagnosis of mitochondrial disease based on a determination&#xD;
             by a physician with expertise in genetics and/or neurology. Supportive evidence may&#xD;
             include genetic testing, muscle biopsy, biochemical testing, neuroimaging or enzyme&#xD;
             analysis consistent with mitochondrial disease.&#xD;
&#xD;
          3. At the time of enrollment, participants must have suspected or confirmed COVID-19 as&#xD;
             defined by&#xD;
&#xD;
               1. New onset of any of the following symptoms after January 2020 without an&#xD;
                  alternative diagnosis: fever, cough, shortness of breath, fatigue, sore throat,&#xD;
                  rhinorrhea, musculoskeletal pain, vomiting, diarrhea, anosmia, neurologic&#xD;
                  decline;&#xD;
&#xD;
                  AND report that testing for COVID-19/SARS-COV-2 is clinically indicated based on&#xD;
                  evaluation by a healthcare provider.&#xD;
&#xD;
                  OR&#xD;
&#xD;
               2. Laboratory confirmed positive testing for COVID-19/SARS-Cov-2 performed at a&#xD;
                  local healthcare setting.&#xD;
&#xD;
        Note: It is well recognized at the time of this protocol that testing for&#xD;
        COVID-19/SARS-Cov-2 is not consistently available or efficient throughout the United&#xD;
        States, particularly in low healthcare resource settings. In order to avoid bias by&#xD;
        limiting recruitment to only those individuals with access to these healthcare resources,&#xD;
        inclusion criteria for participants with acute illness have intentionally been kept&#xD;
&#xD;
        broad. Participants in Group 1 who are initially suspected to have COVID-19 but are later&#xD;
        found to have an alternative infectious illness will be used for comparison studies. Please&#xD;
        also note that there is no minimum weight requirement for Group 1. However, there is a&#xD;
        minimum weight requirement for phlebotomy procedures (See Sections 1.2 and 7.3.1). Group 1&#xD;
        participants who do not meet minimum weight requirements may enroll for records and&#xD;
        questionnaires only.&#xD;
&#xD;
        Group 1b&#xD;
&#xD;
          1. Participants must be two months of age or older.&#xD;
&#xD;
          2. Participants must have a diagnosis of mitochondrial disease based on a determination&#xD;
             by a physician with expertise in genetics and/or neurology. Supportive evidence may&#xD;
             include genetic testing, muscle biopsy, biochemical testing, neuroimaging or enzyme&#xD;
             analysis consistent with mitochondrial disease.&#xD;
&#xD;
          3. At the time of enrollment, participants may not have evidence of any acute infection.&#xD;
&#xD;
        Group 2&#xD;
&#xD;
          1. Participants must be two months of age or older.&#xD;
&#xD;
          2. Participants must weigh greater than 4 kilograms.&#xD;
&#xD;
          3. Participants must be genetically related family member of a participant in Group 1&#xD;
             above.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        An individual who meets any of the following criteria will be excluded from participation&#xD;
        in this study:&#xD;
&#xD;
        Groups 1 a&amp;b&#xD;
&#xD;
          1. Participants who are less than two months of age.&#xD;
&#xD;
          2. Participants who do not have mitochondrial disease.&#xD;
&#xD;
          3. Study team may decline to enroll a participant for other reasons based on clinical&#xD;
             judgement.&#xD;
&#xD;
        Group 2&#xD;
&#xD;
          1. Participants who are less than two months of age.&#xD;
&#xD;
          2. Participants who are not family members of Group 1.&#xD;
&#xD;
          3. Study team may decline to enroll a participant for other reasons based on clinical&#xD;
             judgement.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Months</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eliza M Gordon-Lipkin, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Human Genome Research Institute (NHGRI)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shannon Kruk, R.N.</last_name>
    <phone>(301) 451-9145</phone>
    <email>shannon.kruk@nih.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Eliza M Gordon-Lipkin, M.D.</last_name>
    <phone>(301) 204-4028</phone>
    <email>eliza.gordon-lipkin@nih.gov</email>
  </overall_contact_backup>
  <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>
    <status>Recruiting</status>
    <contact>
      <last_name>For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)</last_name>
      <phone>800-411-1222</phone>
      <phone_ext>TTY8664111010</phone_ext>
      <email>prpl@cc.nih.gov</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2020-HG-0120.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>September 21, 2022</verification_date>
  <study_first_submitted>June 5, 2020</study_first_submitted>
  <study_first_submitted_qc>June 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>September 24, 2022</last_update_submitted>
  <last_update_submitted_qc>September 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Genetics</keyword>
  <keyword>Phenotype</keyword>
  <keyword>Virus</keyword>
  <keyword>Natural History</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Mitochondrial Diseases</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/NCT04419870
org study id: 200120
secondary id: 20-HG-0120
nct id: NCT04419870
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

      Mitochondrial disease is a rare disorder. It can cause poor growth, developmental delays,
      muscle weakness, and other symptoms. The disease is usually inherited. It can be present at
      birth or develop later in life. Infection is a major cause of disease and death in people
      with this disease. Researchers want to learn more about how infection and the declining
      health of people who have this disease may be related to the COVID-19 pandemic. To do this,
      researchers will study the DNA of people who become ill with suspected or confirmed
      coronavirus. Their DNA will be compared to the DNA of their family members.

      Objective:

      To learn more about how genes may play a role in how COVID-19 affects people with
      mitochondrial disease.

      Eligibility:

      People age 2 months and older with mitochondrial disease and a suspected or confirmed
      diagnosis of COVID-19.<TAB>

      Design:

      Participants will complete a questionnaire about their health history. Their medical records
      may be reviewed. They will give a blood sample.

      If the participant becomes ill, they may have a videoconference with a doctor or nurse at the
      NIH to perform a physical exam. They may be contacted after their illness to give updates on
      their health. They may be asked to give extra blood samples or complete extra questionnaires.

      Participants genetic data will be put into a database. The data will be labeled with a code
      and not their name. The data will be shared with other researchers.

      Participation lasts about 1 year. This may be extended if the participant is very ill.
Infection is a major cause of morbidity and mortality individuals with mitochondrial disease,
      frequently triggering metabolic decompensation, multiorgan dysfunction, and neurologic
      deterioration. In the context of the recent COVID19 pandemic, people with mitochondrial
      disease are at increased risk for severe disease and poor outcomes if infected. However, the
      mechanisms for this link between infection and clinical decline are incompletely understood.
      Given that people with mitochondrial disease are particularly susceptible to infection and
      may experience delayed recovery, we hypothesize that this is in part due to immune factors
      that influence host-pathogen interactions. The purpose of this protocol is to collect
      biological specimens to identify immune signatures that contribute to the phenotype of
      infection and outcomes in patients with mitochondrial disease who become ill during the
      COVID19 pandemic. In order to compare these cases with others of similar genetic backgrounds
      and environmental exposures, we will also collect specimens from family members. We will then
      examine how these signatures correlate with comprehensive quantifiable clinical measures
      throughout the course of disease, from presenting symptoms, through acute decompensation,
      stabilization and convalescence. While this protocol is developed during the COVID-19
      pandemic with a focus on a specific infectious pathogen, we hope that this study will extend
      beyond the pandemic in an effort to more broadly understand acute infectious illness in
      patients with mitochondrial disease. Additionally, it will serve as a remote adjunct to the
      NIH MINI Study, a natural history study focused on the immunophenotype of mitochondrial
      disease that is conducted at the NIH Clinical Center.
observational model: Case-Control
time perspective: Prospective
measure: We will perform whole blood transcriptomic analysis, humoral response profiling and soluble mediator profiling.
time frame: Undefined for natural history study
description: To identify immune signatures that associate with host responses to disease that would allow improved patient stratification and identification of potential therapeutic targets to mitigate the severe symptoms and sequelae of infection in mitochondrial disease.
measure: Patient Medical Records for Data Abstraction
time frame: Undefined for natural history study
description: to stratify severity of illness based on clinical factors (e.g. intensive care status, ventilatory support, clinical laboratory data, radiology records)
measure: Patient centered outcomes data via questionnaires
time frame: Undefined for natural history study
description: to understand functional status, healthcare resource access and other sociodynamic factors as they affect the mitochondrial disease community.
arm group label: Group 1a
description: Patients with mitochondrial disease who are ill with suspected or confirmed COVID19
arm group label: Group 1b
description: Patients with mitochondrial disease who are NOT ill with acute infection
arm group label: Group 2
description: Family members of patients with mitochondrial disease in Group 1
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 2 Months
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Eliza M Gordon-Lipkin, M.D.
role: Principal Investigator
affiliation: National Human Genome Research Institute (NHGRI)
last name: Shannon Kruk, R.N.
phone: (301) 451-9145
email: shannon.kruk@nih.gov
last name: Eliza M Gordon-Lipkin, M.D.
phone: (301) 204-4028
email: eliza.gordon-lipkin@nih.gov
facility: 
status: Recruiting
contact: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2020-HG-0120.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor
mesh term: Infections
mesh term: COVID-19
mesh term: Mitochondrial Diseases