<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/NCT04408950</url>
  </required_header>
  <id_info>
    <org_study_id>200084</org_study_id>
    <secondary_id>20-I-0084</secondary_id>
    <nct_id>NCT04408950</nct_id>
  </id_info>
  <brief_title>Sample Collection for Systems Evaluation of Patients With Unknown or Incompletely Characterized Immune Defects</brief_title>
  <official_title>Sample Collection for Systems Evaluation of Patients With Unknown or Incompletely Characterized Immune Defects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</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;
      The immune system defends the body against disease. It has many different parts spread out in&#xD;
&#xD;
      the body, including in the blood and skin. To learn more about it, researchers want to study&#xD;
      samples from people with healthy immune systems and people with conditions that affect how&#xD;
      the immune system works.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To learn about how the different parts of the immune system come together to make a whole.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      People age 2 and older who have a condition that affects the immune system or have a family&#xD;
      member with such a condition.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened with medical and medicine review. Other lab tests may also be&#xD;
      reviewed. Some participants will take a pregnancy test.&#xD;
&#xD;
      Participants will give blood samples. They may also give saliva, stool, and urine samples.&#xD;
&#xD;
      A sterile cotton swab may be rubbed over their skin or inside the cheek or nose to collect&#xD;
      cells.&#xD;
&#xD;
      If participants have samples collected as part of their regular medical care, their doctor&#xD;
      may be asked to send parts of the samples that otherwise would be thrown away. These samples&#xD;
      may be from biopsies, endoscopies, or other procedures.&#xD;
&#xD;
      Some participants may have optional skin punch biopsies. For this, their skin is numbed. Then&#xD;
      a tool removes 1 or 2 small pieces of skin from the forearm or thigh.&#xD;
&#xD;
      Participants medical records will be checked to see if they have any changes in their health&#xD;
      over time. If they have a study visit, they may talk about their medical history and have a&#xD;
      physical exam.&#xD;
&#xD;
      Participation lasts 5 years....&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Immunological disorders predispose affected individuals to a myriad of complications,&#xD;
      including infection, immune dysregulation with autoimmune disease and aberrant inflammatory&#xD;
      responses, and malignancy. Advances in genetic testing have propelled the discovery of the&#xD;
      genetic underpinnings of numerous immunodeficiencies. However, a more complete picture of the&#xD;
      immune system is needed to better characterize patients that present with the signs and&#xD;
      symptoms of immunodeficiency or immune dysregulation in whom there is no identifiable genetic&#xD;
      diagnosis. Many of our diagnostic tools, such as characterization of cell subset frequencies,&#xD;
      look at only one parameter in the immune system, which is typically insufficient to capture&#xD;
      the system s complexity. Systems immunology is a field of research aimed to identify and&#xD;
      understand how the different components of the immune system work together in a coordinated&#xD;
      manner to achieve its functions, such as protecting against pathogens and mounting effective&#xD;
      responses after vaccination. The goal of this study is to collect patient samples to more&#xD;
      deeply phenotype these individuals at the molecular and cellular levels using novel&#xD;
      technologies in order to generate hypotheses regarding disease etiologies and mechanisms in&#xD;
      subjects with an immune disorder without complete characterization or clear genetic etiology.&#xD;
      We also aim to validate a specific observation seen in a previous study of patients with&#xD;
      known monogenic immunological disorders. In the long-term, hypotheses generated in this study&#xD;
      that address clinically significant, actionable questions will be pursued as separate&#xD;
      investigations.&#xD;
&#xD;
      This hypothesis-generating sample collection study will recruit patients with unknown or&#xD;
      incompletely characterized immune defects and their unaffected relatives. Under this&#xD;
      protocol, samples will be collected at the NIH Clinical Center or mailed in for analysis&#xD;
      using systems biology approaches to generate hypotheses regarding the potential etiologies&#xD;
      and mechanisms of these immune defects. Initially, all subjects will give a blood sample and&#xD;
      may give additional samples including saliva, stool, and skin punch biopsies. Subjects will&#xD;
      be enrolled for 5 years and may be asked to give additional samples based on scientific need&#xD;
      or changes in clinical status. Findings relevant to subjects health and medical care will be&#xD;
      returned to them and referring healthcare providers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 12, 2020</start_date>
  <completion_date type="Anticipated">May 1, 2030</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2030</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>CBC with differential, lymphocyte phenotyping, and whole blood RNA expression data analyzed in individuals with unknown or incompletely characterized immune defects.</measure>
    <time_frame>Baseline</time_frame>
    <description>CBC with differential, lymphocyte phenotyping, and whole blood RNA expression data analyzed in individuals with unknown or incompletely characterized immune defects.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CBC with differential and lymphocyte phenotyping in individuals with unknown or incompletely characterized immunological defects compared with age- and gender-matched healthy control</measure>
    <time_frame>Baseline</time_frame>
    <description>CBC with differential and lymphocyte phenotyping in individuals with unknown or incompletely characterized immunological defects compared with age- and gender-matched healthy control</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">400</enrollment>
  <condition>Immunodeficiency</condition>
  <arm_group>
    <arm_group_label>Patients with uncharacterized immune defects</arm_group_label>
    <description>Patients with uncharacterized immune defects</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Unaffected biological relatives</arm_group_label>
    <description>Unaffected biological relatives</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Study participants will be selected or referred to the protocol from other NIH groups whose&#xD;
        patients have an uncharacterized immune defect. Unaffected biological relatives of these&#xD;
        participants may also be recruited.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
               1. Aged greater than or equal to 2 years.&#xD;
&#xD;
               2. Meets 1 of the following criteria:&#xD;
&#xD;
                  a. Patient with a suspected or known/molecularly defined but incompletely&#xD;
                  characterized immune disorder (as determined by a referring NIH study staff&#xD;
                  member) AND meeting at least one of the following:&#xD;
&#xD;
                  i. within 1 year of screening, abnormal immune function demonstrated by at least&#xD;
                  one laboratory test result outside the normal range&#xD;
&#xD;
                  ii. history of severe or atypical infection, immune dysregulation (defined as&#xD;
                  autoimmunity, lymphoproliferation, or HLH), or autoinflammatory symptoms (defined&#xD;
                  as episodic fever often associated with dermatitis, gastrointestinal symptoms,&#xD;
                  and arthropathy).&#xD;
&#xD;
                  b. Biological unaffected relative of an individual meeting criterion 2a but who&#xD;
                  does not meet criterion 2a himself/herself. Unaffected relatives may be mother,&#xD;
                  father, siblings, children, grandparents, aunts, uncles, or first cousins to the&#xD;
                  individual.&#xD;
&#xD;
               3. Willing to allow storage of samples and data for future research.&#xD;
&#xD;
               4. For patients, currently or previously enrolled on an NIH protocol that performs&#xD;
                  WES or WGS and that allows sharing of sequence data.&#xD;
&#xD;
               5. For unaffected relatives, able to provide informed consent.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        Individuals meeting any of the following criteria will be excluded from study&#xD;
        participation:&#xD;
&#xD;
          1. History of secondary causes of immunodeficiency or dysregulation (e.g., HIV infection,&#xD;
             immunodeficiency from chronic use of immunosuppressive or chemotherapeutic agents), at&#xD;
             the discretion of the investigator.&#xD;
&#xD;
          2. Pregnancy.&#xD;
&#xD;
          3. Any condition that, in the opinion of the investigator, contraindicates participation&#xD;
             in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>120 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rachel D Sparks, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Allergy and Infectious Diseases (NIAID)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Laura E Failla, C.R.N.P.</last_name>
    <phone>(240) 669-5323</phone>
    <email>laura.failla@nih.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rachel D Sparks, M.D.</last_name>
    <phone>(240) 292-4642</phone>
    <email>rachel.sparks@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-I-0084.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>September 7, 2023</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>September 8, 2023</last_update_submitted>
  <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Immunological Disorders</keyword>
  <keyword>Monogenic</keyword>
  <keyword>Systems Immunology</keyword>
  <keyword>Phenotype</keyword>
  <keyword>Hypothesis Generating</keyword>
  <keyword>Natural History</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunologic Deficiency Syndromes</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/NCT04408950
org study id: 200084
secondary id: 20-I-0084
nct id: NCT04408950
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

      The immune system defends the body against disease. It has many different parts spread out in

      the body, including in the blood and skin. To learn more about it, researchers want to study
      samples from people with healthy immune systems and people with conditions that affect how
      the immune system works.

      Objective:

      To learn about how the different parts of the immune system come together to make a whole.

      Eligibility:

      People age 2 and older who have a condition that affects the immune system or have a family
      member with such a condition.

      Design:

      Participants will be screened with medical and medicine review. Other lab tests may also be
      reviewed. Some participants will take a pregnancy test.

      Participants will give blood samples. They may also give saliva, stool, and urine samples.

      A sterile cotton swab may be rubbed over their skin or inside the cheek or nose to collect
      cells.

      If participants have samples collected as part of their regular medical care, their doctor
      may be asked to send parts of the samples that otherwise would be thrown away. These samples
      may be from biopsies, endoscopies, or other procedures.

      Some participants may have optional skin punch biopsies. For this, their skin is numbed. Then
      a tool removes 1 or 2 small pieces of skin from the forearm or thigh.

      Participants medical records will be checked to see if they have any changes in their health
      over time. If they have a study visit, they may talk about their medical history and have a
      physical exam.

      Participation lasts 5 years....
Immunological disorders predispose affected individuals to a myriad of complications,
      including infection, immune dysregulation with autoimmune disease and aberrant inflammatory
      responses, and malignancy. Advances in genetic testing have propelled the discovery of the
      genetic underpinnings of numerous immunodeficiencies. However, a more complete picture of the
      immune system is needed to better characterize patients that present with the signs and
      symptoms of immunodeficiency or immune dysregulation in whom there is no identifiable genetic
      diagnosis. Many of our diagnostic tools, such as characterization of cell subset frequencies,
      look at only one parameter in the immune system, which is typically insufficient to capture
      the system s complexity. Systems immunology is a field of research aimed to identify and
      understand how the different components of the immune system work together in a coordinated
      manner to achieve its functions, such as protecting against pathogens and mounting effective
      responses after vaccination. The goal of this study is to collect patient samples to more
      deeply phenotype these individuals at the molecular and cellular levels using novel
      technologies in order to generate hypotheses regarding disease etiologies and mechanisms in
      subjects with an immune disorder without complete characterization or clear genetic etiology.
      We also aim to validate a specific observation seen in a previous study of patients with
      known monogenic immunological disorders. In the long-term, hypotheses generated in this study
      that address clinically significant, actionable questions will be pursued as separate
      investigations.

      This hypothesis-generating sample collection study will recruit patients with unknown or
      incompletely characterized immune defects and their unaffected relatives. Under this
      protocol, samples will be collected at the NIH Clinical Center or mailed in for analysis
      using systems biology approaches to generate hypotheses regarding the potential etiologies
      and mechanisms of these immune defects. Initially, all subjects will give a blood sample and
      may give additional samples including saliva, stool, and skin punch biopsies. Subjects will
      be enrolled for 5 years and may be asked to give additional samples based on scientific need
      or changes in clinical status. Findings relevant to subjects health and medical care will be
      returned to them and referring healthcare providers.
observational model: Cohort
time perspective: Prospective
measure: CBC with differential, lymphocyte phenotyping, and whole blood RNA expression data analyzed in individuals with unknown or incompletely characterized immune defects.
time frame: Baseline
description: CBC with differential, lymphocyte phenotyping, and whole blood RNA expression data analyzed in individuals with unknown or incompletely characterized immune defects.
measure: CBC with differential and lymphocyte phenotyping in individuals with unknown or incompletely characterized immunological defects compared with age- and gender-matched healthy control
time frame: Baseline
description: CBC with differential and lymphocyte phenotyping in individuals with unknown or incompletely characterized immunological defects compared with age- and gender-matched healthy control
arm group label: Patients with uncharacterized immune defects
description: Patients with uncharacterized immune defects
arm group label: Unaffected biological relatives
description: Unaffected biological relatives
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 2 Years
maximum age: 120 Years
healthy volunteers: No
last name: Rachel D Sparks, M.D.
role: Principal Investigator
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
last name: Laura E Failla, C.R.N.P.
phone: (240) 669-5323
email: laura.failla@nih.gov
last name: Rachel D Sparks, M.D.
phone: (240) 292-4642
email: rachel.sparks@nih.gov
facility: 
status: Recruiting
contact: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2020-I-0084.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor
mesh term: Immunologic Deficiency Syndromes