<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/NCT01661010</url>
  </required_header>
  <id_info>
    <org_study_id>120181</org_study_id>
    <secondary_id>12-HG-0181</secondary_id>
    <nct_id>NCT01661010</nct_id>
  </id_info>
  <brief_title>The Clinical Study of Sex Chromosome Variants</brief_title>
  <official_title>The Clinical Study of Patients With Sex Chromosome Variants</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>
      Purpose/Lay Summary: Background:&#xD;
&#xD;
      - Chromosomes are the structures inside of each cell that carry our genetic material (genes).&#xD;
      Certain differences in the sex chromosomes are known to cause various diseases, such as&#xD;
      infertility, Turner syndrome, or Klinefelter syndrome. However, it is not fully understood&#xD;
      why these differences are seen and what clinical findings may be caused with different sex&#xD;
      chromosome variants. This study is seeking to learn more about the genetic and clinical&#xD;
      characteristics of disorders related to the X and Y chromosomes.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      - To study related medical conditions in people with sex chromosome variants.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  Patients with known sex chromosome differences may be eligible to participate.&#xD;
&#xD;
        -  Healthy volunteers age 18 - 55&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened with a physical exam and medical history. Blood and urine&#xD;
           samples will be collected.&#xD;
&#xD;
        -  This study will last about 5 days. Participants will have a variety of endocrine and&#xD;
           other tests. They will provide blood, urine, and semen samples for these tests.&#xD;
&#xD;
        -  Imaging studies of the heart and abdomen will be performed. These tests may include&#xD;
           ultrasounds and magnetic resonance imaging.&#xD;
&#xD;
        -  Participants will also have their vision and hearing checked.&#xD;
&#xD;
        -  Healthy volunteers with have a single day visit for a medical history, physical exam,&#xD;
           and blood and skin samples.&#xD;
&#xD;
        -  Treatment will not be provided as part of this study.&#xD;
&#xD;
        -  Compensation is offered.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Infertility is a disease that affects approximately 10% of couples world-wide. Causes of&#xD;
      infertility are varied and include age-related decline in fecundity, other causes of&#xD;
      ovulatory dysfunction, tubal and pelvic pathology, male causes, idiopathic, and&#xD;
      multifactorial. The underlying genetic causes of infertility are incompletely understood. The&#xD;
      purpose of this study is to increase our understanding of the genetic and clinical&#xD;
      manifestations of infertility related to sex-chromosome variants through detailed physical,&#xD;
      radiologic, and laboratory studies. We will concentrate on a group of patients (both male and&#xD;
      female) with known sex-chromosome variationsfully characterized through genetic sequencing&#xD;
      and karyotyping. Other patients with&#xD;
&#xD;
      sex chromosome variants will be invited depending on the variant described. Patients&#xD;
      recruited and consenting to this study will be evaluated at the NIH Clinical Center&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 30, 2012</start_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>Phenotype</measure>
    <time_frame>Ongoing</time_frame>
    <description>To characterize the physical, reproductive, endocrinologic and radiologic phenotype of a group of patients who have known sex-chromosome structural and copy-number variants.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Spectrum</measure>
    <time_frame>Ongoing</time_frame>
    <description>To examine the spectrum of clinical characteristics of infertility and other conditions related to sex-chromosome variants and facilitate early clinical recognition, diagnostic confirmation, anticipatory management, prognostication, and proper genetic counseling.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">112</enrollment>
  <condition>Male Factor Infertility</condition>
  <condition>Female Factor Infertility</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <description>Family members can serve as control group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sex-linked genes</arm_group_label>
    <description>Patients previously identified through outside research or diagnostic labs as having sex-chromosome variants causing deletion/duplication of sex-linked genes or entire sex chromosomes.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients previously identified through outside research or diagnostic labs as having&#xD;
        sex-chromosome variants causing deletion/duplication of sex-linked genes or entire sex&#xD;
        chromosomes.@@@&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
               1. Patients previously identified through outside research or diagnostic labs as&#xD;
                  having sex-chromosome variants causing deletion/duplication of sex-linked genes&#xD;
                  or entire sex chromosomes, male and female.&#xD;
&#xD;
               2. In the event that a patient with a sex-chromosome variant self-refers to the&#xD;
                  protocol, medical records will be reviewed by a committee to include Dr. David&#xD;
                  Page, Dr. Maximilian Muenke, and others to decide whether the patient is&#xD;
                  appropriate for enrollment in the protocol.&#xD;
&#xD;
               3. Willing family members of subjects enrolled may be enrolled as control subjects.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          1. Anyone unwilling to provide informed consent or assent.&#xD;
&#xD;
          2. We reserve the right to exclude patients with medical conditions that would place a&#xD;
             potential participant at high risk of complications if managed at the NIH clinical&#xD;
             center (ex. dialysis dependency, unstable cardiac conditions, unstable severe&#xD;
             depression/suicidality).&#xD;
&#xD;
          3. We reserve the right to exclude cases that are clearly not related to Ychromosome&#xD;
             variants, infertility or our direct research interests (e.g. infertility with clearly&#xD;
             non-genetic etiology). This almost never happens, and we would attempt to make&#xD;
             referrals to a more appropriate investigator.&#xD;
&#xD;
        It is our intention to try to remove as many economic, cultural, geographic, racial, and&#xD;
        gender barriers as we reasonably can to promote a diverse participation of infertility&#xD;
        cases for research purposes.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ashley J Buscetta, C.R.N.P.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Human Genome Research Institute (NHGRI)</affiliation>
  </overall_official>
  <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>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2012-HG-0181.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Brandell RA, Mielnik A, Liotta D, Ye Z, Veeck LL, Palermo GD, Schlegel PN. AZFb deletions predict the absence of spermatozoa with testicular sperm extraction: preliminary report of a prognostic genetic test. Hum Reprod. 1998 Oct;13(1O):2812-5. doi: 10.1093/humrep/13.10.2812.</citation>
    <PMID>9804236</PMID>
  </reference>
  <reference>
    <citation>Bondy CA; Turner Syndrome Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007 Jan;92(1):10-25. doi: 10.1210/jc.2006-1374. Epub 2006 Oct 17.</citation>
    <PMID>17047017</PMID>
  </reference>
  <reference>
    <citation>Berta P, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow PN, Fellous M. Genetic evidence equating SRY and the testis-determining factor. Nature. 1990 Nov 29;348(6300):448-50. doi: 10.1038/348448A0.</citation>
    <PMID>2247149</PMID>
  </reference>
  <verification_date>June 9, 2023</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <last_update_submitted>August 4, 2023</last_update_submitted>
  <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Infertility</keyword>
  <keyword>Turner Syndrome</keyword>
  <keyword>X-Chromosome</keyword>
  <keyword>Y-Chromosome</keyword>
  <keyword>Aneuploidy</keyword>
  <keyword>Natural History</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT01661010
org study id: 120181
secondary id: 12-HG-0181
nct id: NCT01661010
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Purpose/Lay Summary: Background:

      - Chromosomes are the structures inside of each cell that carry our genetic material (genes).
      Certain differences in the sex chromosomes are known to cause various diseases, such as
      infertility, Turner syndrome, or Klinefelter syndrome. However, it is not fully understood
      why these differences are seen and what clinical findings may be caused with different sex
      chromosome variants. This study is seeking to learn more about the genetic and clinical
      characteristics of disorders related to the X and Y chromosomes.

      Objectives:

      - To study related medical conditions in people with sex chromosome variants.

      Eligibility:

        -  Patients with known sex chromosome differences may be eligible to participate.

        -  Healthy volunteers age 18 - 55

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected.

        -  This study will last about 5 days. Participants will have a variety of endocrine and
           other tests. They will provide blood, urine, and semen samples for these tests.

        -  Imaging studies of the heart and abdomen will be performed. These tests may include
           ultrasounds and magnetic resonance imaging.

        -  Participants will also have their vision and hearing checked.

        -  Healthy volunteers with have a single day visit for a medical history, physical exam,
           and blood and skin samples.

        -  Treatment will not be provided as part of this study.

        -  Compensation is offered.
Infertility is a disease that affects approximately 10% of couples world-wide. Causes of
      infertility are varied and include age-related decline in fecundity, other causes of
      ovulatory dysfunction, tubal and pelvic pathology, male causes, idiopathic, and
      multifactorial. The underlying genetic causes of infertility are incompletely understood. The
      purpose of this study is to increase our understanding of the genetic and clinical
      manifestations of infertility related to sex-chromosome variants through detailed physical,
      radiologic, and laboratory studies. We will concentrate on a group of patients (both male and
      female) with known sex-chromosome variationsfully characterized through genetic sequencing
      and karyotyping. Other patients with

      sex chromosome variants will be invited depending on the variant described. Patients
      recruited and consenting to this study will be evaluated at the NIH Clinical Center
observational model: Cohort
time perspective: Prospective
measure: Phenotype
time frame: Ongoing
description: To characterize the physical, reproductive, endocrinologic and radiologic phenotype of a group of patients who have known sex-chromosome structural and copy-number variants.
measure: Spectrum
time frame: Ongoing
description: To examine the spectrum of clinical characteristics of infertility and other conditions related to sex-chromosome variants and facilitate early clinical recognition, diagnostic confirmation, anticipatory management, prognostication, and proper genetic counseling.
arm group label: Control
description: Family members can serve as control group
arm group label: Sex-linked genes
description: Patients previously identified through outside research or diagnostic labs as having sex-chromosome variants causing deletion/duplication of sex-linked genes or entire sex chromosomes.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ashley J Buscetta, C.R.N.P.
role: Principal Investigator
affiliation: National Human Genome Research Institute (NHGRI)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2012-HG-0181.html
description: NIH Clinical Center Detailed Web Page
citation: Brandell RA, Mielnik A, Liotta D, Ye Z, Veeck LL, Palermo GD, Schlegel PN. AZFb deletions predict the absence of spermatozoa with testicular sperm extraction: preliminary report of a prognostic genetic test. Hum Reprod. 1998 Oct;13(1O):2812-5. doi: 10.1093/humrep/13.10.2812.
PMID: 9804236
citation: Bondy CA; Turner Syndrome Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007 Jan;92(1):10-25. doi: 10.1210/jc.2006-1374. Epub 2006 Oct 17.
PMID: 17047017
citation: Berta P, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow PN, Fellous M. Genetic evidence equating SRY and the testis-determining factor. Nature. 1990 Nov 29;348(6300):448-50. doi: 10.1038/348448A0.
PMID: 2247149
responsible party type: Sponsor
mesh term: Infertility
sharing ipd: Undecided